Acarbose

Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthritis

Type of study: non-rct experimental

Number of citations: 33

Year: 2020

Authors: Lingshu Zhang, Pingfang Song, Xiaowei Zhang, C. Metea, M. Schleisman, L. Karstens, Eric Y. S. Leung, Jun Zhang, Qiang Xu, Yi Liu, M. Asquith, C. Chu

Journal: Frontiers in Pharmacology

Journal ranking: Q1

Key takeaways: Acarbose reduces arthritis incidence and severity by regulating Th17/Treg cells in the intestinal mucosal immunity, potentially benefiting rheumatoid arthritis management.

Abstract: Acarose is an anti-diabetic drug and exhibits anti-arthritic effects. We hypothesized that acarbose influences the gut microbiota to affect the course of arthritis and tested this hypothesis in a collagen-induced arthritis (CIA) murine model. Acarbose in drinking water was administered via gastric gavage started prior to or at the time of CIA induction. Gut microbiota were evaluated with 16S rRNA gene sequencing from fecal pellets collected prior to arthritis induction, during onset of arthritis, and after treatment. Immune response was evaluated by measuring changes in T helper-17 (Th17) and T regulatory (Treg) cells in the spleen and intestine, as well as serum cytokine levels. Before induction of CIA, acarbose significantly reduced the incidence of arthritis and attenuated clinical severity of arthritis. The frequency of Th17 cells was significantly decreased in the intestinal lamina propria in acarbose treated mice. Mice that were treated with acarbose showed significantly increased CD4+CD25+Foxp3+ Treg cells with elevation of Helios and CCR6. A remarkable alteration in microbial community was observed in acarbose treated mice. Bacterial diversity and richness in mice with arthritis were significantly lower than those in acarbose treated groups. The frequency of Firmicutes was significantly reduced after arthritis onset but was restored after treatment with acarbose. The frequency of Lactobacillus, Anaeroplasma, Adlercreutzia, RF39 and Corynebacterium was significantly higher in control groups than in acarbose treated, while Oscillospira, Desulfovibrio and Ruminococcus enriched in acarbose treated group. Miglitol, another α-glucosidase inhibitor showed a similar but less potent anti-arthritic effect to that of acarbose. These data demonstrate that acarbose alleviated CIA through regulation of Th17/Treg cells in the intestinal mucosal immunity, which may have resulted from the impact of acarbose on gut microbial community. Inexpensive antidiabetic drugs with an excellent safety profile are potentially useful for managing rheumatoid arthritis.

Reducing the intestinal side effects of acarbose by baicalein through the regulation of gut microbiota: An in vitro study.

Type of study: non-rct in vitro

Number of citations: 44

Year: 2022

Authors: Yuesheng Dong, Li-na Sui, Fan Yang, Xinxiu Ren, Y.-Q. Xing, Z. Xiu

Journal: Food chemistry

Journal ranking: Q1

Key takeaways: Combining baicalein with acarbose reduces intestinal side effects by regulating gut microbiota, potentially enhancing the efficacy of oral hypoglycemic agents with fewer side effects.

Starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation in rats treated with the α-glucosidase inhibitor acarbose

Type of study: non-rct experimental

Number of citations: 61

Year: 2004

Authors: M. Dehghan-Kooshkghazi, J. Mathers

Journal: British Journal of Nutrition

Journal ranking: Q1

Key takeaways: Acarbose treatment suppresses starch digestion in the small bowel but compensates with large-bowel fermentation, with no adverse effects on large-bowel function.

Abstract: Acarbose (Glucobay®; Bayer) is an α-glucosidase inhibitor used to treat diabetes and which may have a role in the prevention of type 2 diabetes. The present study investigated the effects of acarbose treatment on the site and extent of starch digestion, large-bowel fermentation and intestinal mucosal cell proliferation. Eighteen young male Wistar rats were fed ‘Westernised’ diets containing 0, 250 and 500mg acarbose/kg (six rats/diet) for 21d. For most variables measured, both acarbose doses had similar effects. Acarbose treatment suppressed starch digestion in the small bowel but there was compensatory salvage by bacterial fermentation in the large bowel. This was accompanied by a substantial hypertrophy of small- and large-bowel tissue and a consistent increase in crypt width along the intestine. Caecal total SCFA pool size was increased more than 4-fold, with even bigger increases for butyrate. These changes in butyrate were reflected in increased molar proportions of butyrate in blood from both the portal vein and heart. There was little effect of acarbose administration on crypt-cell proliferation (significant increase for mid-small intestine only). This is strong evidence against the hypothesis that increased fermentation and increased supply of butyrate enhances intestinal mucosal cell proliferation. In conclusion, apart from the increased faecal loss of starch, there was no evidence of adverse effects of acarbose on the aspects of large-bowel function investigated.

Acarbose, lente carbohydrate, and prebiotics promote metabolic health and longevity by stimulating intestinal production of GLP-1

Type of study:

Number of citations: 41

Year: 2015

Authors: M. McCarty, J. DiNicolantonio

Journal: Open Heart

Journal ranking: Q1

Key takeaways: Acarbose, lente carbohydrate, and prebiotics promote metabolic health and longevity by stimulating intestinal production of GLP-1, which protects against vascular endothelium, liver, heart, pancreatic cells, and brain.

Abstract: The α-glucosidase inhibitor acarbose, which slows carbohydrate digestion and blunts postprandial rises in plasma glucose, has long been used to treat patients with type 2 diabetes or glucose intolerance. Like metformin, acarbose tends to aid weight control, postpone onset of diabetes and decrease risk for cardiovascular events. Acarbose treatment can favourably affect blood pressure, serum lipids, platelet aggregation, progression of carotid intima-media thickness and postprandial endothelial dysfunction. In mice, lifetime acarbose feeding can increase median and maximal lifespan—an effect associated with increased plasma levels of fibroblast growth factor 21 (FGF21) and decreased levels of insulin-like growth factor-I (IGF-I). There is growing reason to suspect that an upregulation of fasting and postprandial production of glucagon-like peptide-1 (GLP-1)—stemming from increased delivery of carbohydrate to L cells in the distal intestinal tract—is largely responsible for the versatile health protection conferred by acarbose. Indeed, GLP-1 exerts protective effects on vascular endothelium, the liver, the heart, pancreatic β cells, and the brain which can rationalise many of the benefits reported with acarbose. And GLP-1 may act on the liver to modulate its production of FGF21 and IGF-I, thereby promoting longevity. The benefits of acarbose are likely mimicked by diets featuring slowly-digested ‘lente’ carbohydrate, and by certain nutraceuticals which can slow carbohydrate absorption. Prebiotics that promote colonic generation of short-chain fatty acids represent an alternative strategy for boosting intestinal GLP-1 production. The health benefits of all these measures presumably would be potentiated by concurrent use of dipeptidyl peptidase 4 inhibitors, which slow the proteolysis of GLP-1 in the blood.

Muribaculaceae Genomes Assembled from Metagenomes Suggest Genetic Drivers of Differential Response to Acarbose Treatment in Mice

Type of study: non-rct experimental

Number of citations: 79

Year: 2020

Authors: Byron J. Smith, Richard A. Miller, T. Schmidt

Journal: mSphere

Journal ranking: Q1

Key takeaways: Acarbose treatment in mice increases the abundance of certain gut bacteria, including Muribaculaceae, which produce propionate, potentially benefiting gut health and longevity.

Abstract: The drug acarbose is used to treat diabetes by preventing the breakdown of starch in the small intestine, resulting in dramatic changes in the abundance of some members of the gut microbiome and its fermentation products. In mice, several of the bacteria that respond most positively are classified in the family Muribaculaceae, members of which produce propionate as a primary fermentation product. ABSTRACT The drug acarbose is used to treat diabetes and, by inhibiting α-amylase in the small intestine, increases the amount of starch entering the lower digestive tract. This results in changes to the composition of the microbiota and their fermentation products. Acarbose also increases longevity in mice, an effect that has been correlated with increased production of the short-chain fatty acids propionate and butyrate. In experiments replicated across three study sites, two distantly related species in the bacterial family Muribaculaceae were dramatically more abundant in acarbose-treated mice, distinguishing these responders from other members of the family. Bacteria in the family Muribaculaceae are predicted to produce propionate as a fermentation end product and are abundant and diverse in the guts of mice, although few isolates are available. We reconstructed genomes from metagenomes (MAGs) for nine populations of Muribaculaceae to examine factors that distinguish species that respond positively to acarbose. We found two closely related MAGs (B1A and B1B) from one responsive species that both contain a polysaccharide utilization locus with a predicted extracellular α-amylase. These genomes also shared a periplasmic neopullulanase with another, distantly related MAG (B2) representative of the only other responsive species. This gene differentiated these three MAGs from MAGs representative of nonresponding species. Differential gene content in B1A and B1B may be associated with the inconsistent response of this species to acarbose across study sites. This work demonstrates the utility of culture-free genomics for inferring the ecological roles of gut bacteria, including their response to pharmaceutical perturbations. IMPORTANCE The drug acarbose is used to treat diabetes by preventing the breakdown of starch in the small intestine, resulting in dramatic changes in the abundance of some members of the gut microbiome and its fermentation products. In mice, several of the bacteria that respond most positively are classified in the family Muribaculaceae, members of which produce propionate as a primary fermentation product. Propionate has been associated with gut health and increased longevity in mice. We found that genomes of the most responsive Muribaculaceae showed signs of specialization for starch fermentation, presumably providing them a competitive advantage in the large intestine of animals consuming acarbose. Comparisons among genomes enhance existing models for the ecological niches occupied by members of this family. In addition, genes encoding one type of enzyme known to participate in starch breakdown were found in all three genomes from responding species but none of the other genomes.

Acarbose improved survival for Apc+/Min mice

Type of study: non-rct experimental

Number of citations: 18

Year: 2020

Authors: Sherry G. Dodds, M. Parihar, M. Javors, J. Nie, N. Musi, Z. Dave Sharp, P. Hasty

Journal: Aging Cell

Journal ranking: Q1

Key takeaways: Acarbose improves survival in Apc+/Min mice by improving carbohydrate metabolism, but its effects are independent of cancer, suggesting the importance of improved carbohydrate metabolism on survival.

Abstract: Acarbose blocks the digestion of complex carbohydrates, and the NIA Intervention Testing Program (ITP) found that it improved survival when fed to mice. Yet, we do not know if lifespan extension was caused by its effect on metabolism with regard to the soma or cancer suppression. Cancer caused death for ~80% of ITP mice. The ITP found rapamycin, an inhibitor to the pro‐growth mTORC1 (mechanistic target of rapamycin complex 1) pathway, improved survival and it suppressed tumors in Apc+/Min mice providing a plausible rationale to ask if acarbose had a similar effect. Apc+/Min is a mouse model prone to intestinal polyposis and a mimic of familial adenomatous polyposis in people. Polyp‐associated anemia contributed to their death. To address this knowledge gap, we fed two doses of acarbose to Apc+/Min mice. Acarbose improved median survival at both doses. A cross‐sectional analysis was performed next. At both doses, ACA fed mice exhibited reduced intestinal crypt depth, weight loss despite increased food consumption and reduced postprandial blood glucose and plasma insulin, indicative of improved insulin sensitivity. Dose‐independent and dose‐dependent compensatory liver responses were observed for AMPK and mTORC1 activities, respectively. Only mice fed the high dose diet exhibited reductions in tumor number with higher hematocrits. Because low‐dose acarbose improved lifespan but failed to reduced tumors, its effects seem to be independent of cancer. These data implicate the importance of improved carbohydrate metabolism on survival.

The effect of acarbose on the intestinal metabolism of glucose in vitro

Type of study: non-rct in vitro

Number of citations: 2

Year: 2004

Authors: M. A. Gómez-Zubeldia, F. Ropero, P. Sanchez-Casas, M. Tormo, E. Blázquez, J. Campillo

Journal: Acta Diabetologica

Journal ranking: Q1

Key takeaways: Acarbose does not influence the metabolic utilization of glucose in the intestinal lumen, as shown in vitro.

Abstract: The effect of acarbose on the intestinal metabolism of glucose was investigated using an in vitro perfused preparation of the isolated rat small intestinepancreas. In preparations perfused without intraluminal sucrose administration, the total glucose recovered in the portal effluent and the portal values of lactate, pyruvate and alanine did not depend on whether or not acarbose [1.5 mg/kg body weight (b.w.)] was present in the intestinal lumen. The intestinal glucose and lactate contents were very low at the end of the experiment, and identical with or without acarbose. Insulin and glucagon concentrations remained constant during the whole perfusion period. After intraluminal administration of sucrose a clear increase in portal glucose concentration was observed, which was severely reduced by acarbose administration; no changes in portal levels of lactate, pyruvate, alanine, insulin and glucagon were observed. The intestinal content of sucrose at the end of the study was significantly higher in the presence of acarbose (1.5 mg/kg b.w.), while the glucose concentration was low both with and without acarbose (0.20±0.08 vs 0.29±0.09 mmol/l respectively). These results suggest that acarbose does not influence the metabolic utilization of the glucose being translocated from the lumen.

Acarbose is again on the stage

Type of study:

Number of citations: 26

Year: 2022

Authors: M. Altay

Journal: World Journal of Diabetes

Journal ranking: brak

Key takeaways: Acarbose may once again be considered a first-choice antidiabetic agent due to its positive effect on GLP-1 and cardiovascular protection, making it a potential alternative to incretin-based treatments.

Abstract: Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years; it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine. Since incretin-based treatments have been preferred over the last 10 to 15 years, the use of acarbose is not as common in treating type 2 diabetes as before. Some studies have shown that acarbose also produces a weight-loss effect by increasing glucagon-like peptide 1 (GLP-1). The positive effect of acarbose on GLP-1, and increasing evidence that it provides cardiovascular protection, suggests that acarbose may again be considered among the first-choice antidiabetic agents, as it was in the 1990s.

Acarbose, as a potential drug, effectively blocked the dynamic metastasis of EV71 from the intestine to the whole body.

Type of study: non-rct experimental

Number of citations: 6

Year: 2020

Authors: Qingyuan Feng, Hui-Ying Zhou, Xiyue Zhang, Xuan Liu, Jie Wang, Cuiping Zhang, Xiaojing Ma, Chunju Quan, Zhongliang Zheng

Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases

Journal ranking: Q1

Key takeaways: Acarbose shows potential as a preventive medicine against EV71 infection by blocking its dynamic metastasis from the intestine to the whole body.

Changes in the gut microbiome and fermentation products concurrent with enhanced longevity in acarbose-treated mice

Type of study: non-rct experimental

Number of citations: 246

Year: 2019

Authors: Byron J. Smith, Richard A. Miller, A. Ericsson, D. Harrison, R. Strong, T. Schmidt

Journal: BMC Microbiology

Journal ranking: Q2

Key takeaways: Acarbose treatment in mice increases lifespan by 20% in males and 5% in females, with changes in gut microbiota and fermentation products contributing to the longevity-enhancing effects.

Abstract: Treatment with the α-glucosidase inhibitor acarbose increases median lifespan by approximately 20% in male mice and 5% in females. This longevity extension differs from dietary restriction based on a number of features, including the relatively small effects on weight and the sex-specificity of the lifespan effect. By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites.Microbial communities and the concentrations of SCFAs in the feces of mice treated with acarbose were notably different from those of control mice. At all three study sites, the bloom of a single bacterial taxon was the most obvious response to acarbose treatment. The blooming populations were classified to the largely uncultured Bacteroidales family Muribaculaceae and were the same taxonomic unit at two of the three sites. Propionate concentrations in feces were consistently elevated in treated mice, while the concentrations of acetate and butyrate reflected a dependence on study site. Across all samples, Muribaculaceae abundance was strongly correlated with propionate and community composition was an important predictor of SCFA concentrations. Cox proportional hazards regression showed that the fecal concentrations of acetate, butyrate, and propionate were, together, predictive of mouse longevity even while controlling for sex, site, and acarbose.We observed a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the responses illustrate the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, testing causal roles of SCFAs in the observed effects of acarbose.

Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.

Type of study: non-rct experimental

Number of citations: 7

Year: 2024

Authors: Shi-Long Zhang, Xin Wang, Qing-Qing Cai, Chen Chen, Zheng-yan Zhang, Ya-Yun Xu, Meng-Xuan Yang, Qingan Jia, Yan Wang, Zhiming Wang

Journal: Nature metabolism

Journal ranking: Q1

Key takeaways: Acarbose enhances the efficacy of anti-PD-1 therapy by modulating gut microbiota, promoting CD8+ T cell recruitment, and enhancing tumor response to anti-PD-1 therapy.

Two weeks of acarbose treatment shows no effect on gut microbiome composition in patients with type 2 diabetes: a randomised, placebo-controlled, double-blind, crossover study

Type of study: rct

Number of citations: 0

Year: 2024

Authors: N. B. Dalsgaard, L. Gasbjerg, L. S. Hansen, Dennis S Nielsen, T. S. Rasmussen, Filip K. Knop

Journal: Endocrine Connections

Journal ranking: Q2

Key takeaways: Acarbose treatment for 14 days showed only minor effects on gut microbiome composition in patients with metformin-treated type 2 diabetes, with increased relative abundances of Klebsiella spp. and Escherichia coli.

Abstract: Aim The alpha-glucosidase inhibitor acarbose is approved for the treatment of type 2 diabetes (T2D). It acts in the lumen of the gut by reducing intestinal hydrolysis and absorption of ingested carbohydrates. This reduces postprandial blood glucose concentration and increases the content of carbohydrates in the distal parts of the intestine potentially influencing gut microbiome (GM) composition and possibly impacting the gut microbiome (GM) dysbiosis associated with T2D. Here, we investigated the effect of acarbose on GM composition in patients with T2D. Methods Faecal samples were collected in a previously conducted randomised, placebo-controlled, double-blind, crossover study in which 15 individuals with metformin-treated T2D (age 57–85 years, HbA1c 40–74 mmol/mol, BMI 23.6–34.6 kg/m2) were subjected to two 14-day treatment periods with acarbose and placebo, respectively, separated by a 6-week wash-out period. Faecal samples were collected before and by the end of each treatment period. The GM profiles were evaluated by 16S rRNA gene amplicon sequencing. Results The GM profiles after the treatment periods with acarbose or placebo remained unaffected (P > 0.7) when compared with the GM profiles before treatment. This applied to the analysis of within-sample diversity (α-diversity) and between-sample bacterial composition diversity (β-diversity). Additionally, no dominant bacterial species differentiated the treatment groups, and only minor increases in the relative abundances of Klebsiella spp. and Escherichia coli (P < 0.05) were observed after acarbose treatment. Conclusion In patients with metformin-treated T2D, 14 days of treatment with acarbose showed only minor effects on GM as seen in increased relative abundances of Klebsiella spp. and Escherichia coli.

Inactivation of the antidiabetic drug acarbose by human intestinal microbial-mediated degradation

Type of study: non-rct experimental

Number of citations: 21

Year: 2023

Authors: Jinzhong Tian, Chong Li, Zhixiang Dong, Yunpeng Yang, Jing Xing, Pei-Jun Yu, Ying Xin, Fengmei Xu, Lianwei Wang, Yahui Mu, Xiangyang Guo, Qiang Sun, Guoping Zhao, Yang Gu, G. Qin, Weihong Jiang

Journal: Nature Metabolism

Journal ranking: Q1

Key takeaways: Intestinal bacteria, Klebsiella grimontii TD1, may contribute to acarbose resistance in patients, potentially representing a clinically relevant example of non-antibiotic drug resistance.

The Glucoamylase Inhibitor Acarbose Has a Diet-Dependent and Reversible Effect on the Murine Gut Microbiome

Type of study: non-rct experimental

Number of citations: 59

Year: 2019

Authors: Nielson T. Baxter, Nicholas A. Lesniak, H. Sinani, P. Schloss, N. Koropatkin

Journal: mSphere

Journal ranking: brak

Key takeaways: Acarbose treatment alters the gut bacterial community structure in mice, but the changes are reversible and dependent on the diet.

Abstract: The gut microbial community has a profound influence on host physiology in both health and disease. In diabetic individuals, the gut microbiota can affect the course of disease, and some medications for diabetes, including metformin, seem to elicit some of their benefits via an interaction with the microbiota. Here, we report that acarbose, a glucoamylase inhibitor for type 2 diabetes, changes the murine gut bacterial community structure in a reversible and diet-dependent manner. In both high-starch and high-fiber diet backgrounds, acarbose treatment results in increased short-chain fatty acids, particularly butyrate, as measured in stool samples. As we learn more about how human disease is affected by the intestinal bacterial community, the interplay between medications such as acarbose and the diet will become increasingly important to evaluate. ABSTRACT Acarbose is a safe and effective medication for type 2 diabetes that inhibits host glucoamylases to prevent starch digestion in the small intestines and thus decrease postprandial blood glucose levels. This results in an increase in dietary starch in the distal intestine, where it becomes food for the gut bacterial community. Here, we examined the effect of acarbose therapy on the gut community structure in mice fed either a high-starch (HS) or high-fiber diet rich in plant polysaccharides (PP). The fecal microbiota of animals consuming a low dose of acarbose (25 ppm) was not significantly different from that of control animals that did not receive acarbose. However, a high dose of acarbose (400 ppm) with the HS diet resulted in a substantial change to the microbiota structure. Most notably, the HS diet with a high dose of acarbose lead to an expansion of the Bacteroidaceae and Bifidobacteriaceae and a decrease in the Verrucomicrobiaceae (such as Akkermansia muciniphila) and the Bacteroidales S24-7. Once acarbose treatment ceased, the community composition quickly reverted to mirror that of the control group, suggesting that acarbose does not irreversibly alter the gut community. The high dose of acarbose in the PP diet resulted in a distinct community structure with increased representation of Bifidobacteriaceae and Lachnospiraceae. Short-chain fatty acids (SCFAs) measured from stool samples were increased, especially butyrate, as a result of acarbose treatment in both diets. These data demonstrate the potential of acarbose to change the gut community structure and increase beneficial SCFA output in a diet-dependent manner. IMPORTANCE The gut microbial community has a profound influence on host physiology in both health and disease. In diabetic individuals, the gut microbiota can affect the course of disease, and some medications for diabetes, including metformin, seem to elicit some of their benefits via an interaction with the microbiota. Here, we report that acarbose, a glucoamylase inhibitor for type 2 diabetes, changes the murine gut bacterial community structure in a reversible and diet-dependent manner. In both high-starch and high-fiber diet backgrounds, acarbose treatment results in increased short-chain fatty acids, particularly butyrate, as measured in stool samples. As we learn more about how human disease is affected by the intestinal bacterial community, the interplay between medications such as acarbose and the diet will become increasingly important to evaluate.

Effects of acarbose on fecal nutrients, colonic pH, and short-chain fatty acids and rectal proliferative indices.

Type of study: non-rct experimental

Number of citations: 70

Year: 1996

Authors: Peter R. Holt, E. Atillasoy, John Lindenbaum, Sam B. Ho, J. Lupton, Donald J. McMahon, Steven F. Moss

Journal: Metabolism: clinical and experimental

Journal ranking: Q1

Key takeaways: Long-term acarbose administration does not negatively affect colonic function or fecal nutrient output, and increased fecal short-chain fatty acids and butyrate may reduce the risk of colonic neoplasia.

Effects of Acarbose on the Gut Microbiota of Prediabetic Patients: A Randomized, Double-blind, Controlled Crossover Trial

Type of study: rct

Number of citations: 148

Year: 2017

Authors: Xiuying Zhang, Zhiwei Fang, Chunfang Zhang, Huihua Xia, Zhuye Jie, Xueyao Han, Ying-li Chen, L. Ji

Journal: Diabetes Therapy

Journal ranking: Q2

Key takeaways: Acarbose treatment selectively modulates gut microbiota in prediabetic patients, potentially contributing to its benefits for type 2 diabetes mellitus prevention and treatment.

Abstract: The α-glucosidase inhibitor acarbose is an efficacious medicine for the treatment and prevention of type 2 diabetes mellitus (T2DM). However, the response of gut microbiota to acarbose is important, as the microbiota may have a critical role in the development of metabolic diseases, and acarbose is metabolized exclusively within the gastrointestinal tract. We explored the changes in the proportion and diversity of gut microbiota before and after treatment with acarbose in patients with prediabetes. We designed a randomized, double-blind, controlled crossover trial in which 52 Chinese patients with prediabetes by an oral glucose tolerance test (OGTT) with a BMI of 18–35 kg/m2 were randomly allocated to treatment with acarbose or placebo. Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. Of the 52 participants who entered the study, 40 (76.9%) completed the protocol. On the basis of the operational taxonomic unit (OTU) profiles, a total of 107 OTUs were significantly altered after acarbose treatment, with 76 (71%) assigned to the order of Clostridiales. Ruminococcaceae (15 OTUs) and Lachnospiraceae (22 OTUs) decreased in response to acarbose, and 48 OTUs increased by 12.8-fold, including Lactobacillaceae (8 of 9 belonging to Lactobacillus), Ruminococcaceae (6 of 11 belonging to Faecalibacterium), and Veillonellaceae (8 of 15 belonging to Dialister). At genera level, five flourished after treatment with acarbose, including Lactobacillus and Dialister, while Butyricicoccus, Phascolarctobacterium, and Ruminococcus were inhibited. This study suggests that the benefits of acarbose for T2DM may correlate with the selective modulation of the gut microbiota. Chinese Clinical Trial Register number, ChiCTR-TTRCC-13004112.

Acarbose enhances human colonic butyrate production.

Type of study: rct

Number of citations: 106

Year: 1997

Authors: G. Weaver, C. T. Tangel, J. Krause, M. Parfitt, P. Jenkins, Joanne M. Rader, B. Lewis, T. Miller, M. Wolin

Journal: The Journal of nutrition

Journal ranking: Q1

Key takeaways: Acarbose increases colonic butyrate production by reducing starch absorption, expanding starch-fermenting and butyrate-producing bacteria, and inhibiting starch use by acetate- and propionate-producing bacteria.

Abstract: Earlier studies suggest that butyrate has colonic differentiating and nutritional effects and that acarbose increases butyrate production. To determine the effects of acarbose on colonic fermentation, subjects were given 50-200 mg acarbose or placebo (cornstarch), three times per day, with meals in a double-blind crossover study. Fecal concentrations of starch and starch-fermenting bacteria were measured and fecal fermentation products determined after incubation of fecal suspensions with and without added substrate for 6 and 24 h. Substrate additions were cornstarch, cornstarch plus acarbose and potato starch. Dietary starch consumption was similar during acarbose and placebo treatment periods, but fecal starch concentrations were found to be significantly greater with acarbose treatment. Ratios of starch-fermenting to total anaerobic bacteria were also significantly greater with acarbose treatment. Butyrate in feces, measured either as concentration or as percentage of total short-chain fatty acids, was significantly greater with acarbose treatment than with placebo treatment. Butyrate ranged from 22.3 to 27.5 mol/100 mol for the 50-200 mg, three times per day doses of acarbose compared with 18.3-19.3 mol/100 mol for the comparable placebo periods. The propionate in fecal total short-chain fatty acids was significantly less with acarbose treatment (10.7-12.1 mol/100 mol) than with placebo treatment (13.7-14.2 mol/100 mol). Butyrate production was significantly greater in fermentations in samples collected during acarbose treatment, whereas production of acetate and propionate was significantly less. Fermentation decreased when acarbose was added directly to cornstarch fermentations. Acarbose effectively augmented colonic butyrate production by several mechanisms; it reduced starch absorption, expanded concentrations of starch-fermenting and butyrate-producing bacteria and inhibited starch use by acetate- and propionate-producing bacteria.

Acarbose diminishes postprandial suppression of bone resorption in patients with type 2 diabetes.

Type of study: rct

Number of citations: 4

Year: 2023

Authors: Niels B Dalsgaard, L. Gasbjerg, M. M. Helsted, L. S. Hansen, Nina L. Hansen, Kirsa Skov-Jeppesen, B. Hartmann, J. Holst, T. Vilsbøll, F. Knop

Journal: Bone

Journal ranking: Q1

Key takeaways: Acarbose treatment reduces postprandial suppression of bone resorption in patients with type 2 diabetes, potentially due to increased GLP-1 secretion and reduced factors reducing bone resorption.

Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

Type of study: rct

Number of citations: 234

Year: 2017

Authors: R. Holman, R. Coleman, J. Chan, J. Chiasson, Huimei Feng, J. Ge, H. Gerstein, R. Gray, Y. Huo, Zhihui Lang, J. McMurray, L. Rydén, Stefan Schröder, Yihong Sun, M. Theodorakis, M. Tendera, L. Tucker, J. Tuomilehto, Yidong Wei, Wenying Yang, Duolao Wang, D. Hu, C. Pan

Journal: The lancet. Diabetes & endocrinology

Journal ranking: Q1

Key takeaways: Acarbose did not reduce the risk of major adverse cardiovascular events in Chinese patients with coronary heart disease and impaired glucose tolerance, but did reduce the incidence of diabetes.

Acarbose impairs gut Bacteroides growth by targeting intracellular glucosidases

Type of study:

Number of citations: 0

Year: 2024

Authors: Haley A Brown, Adeline L Morris, Nicholas A. Pudlo, Ashley E. Hopkins, Eric C. Martens, Jonathan L. Golob, N. Koropatkin

Journal: mBio

Journal ranking: Q1

Key takeaways: Acarbose impairs gut Bacteroides growth by targeting intracellular glucosidases, with two gut species, Bacteroides ovatus and Bacteroides thetaiotaomicron, responding differently to the drug, suggesting the gut microbiome may

Abstract: ABSTRACT Acarbose is a type 2 diabetes medicine that prevents dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the Bacteroides genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading Bacteroides, Bacteroides ovatus (Bo), and Bacteroides thetaiotaomicron (Bt). Bt growth on starch polysaccharides is severely impaired by acarbose, whereas Bo growth is much less affected by the drug. The Bacteroides use a starch utilization system (Sus) to grow on starch. We hypothesized that Bo and Bt Sus enzymes are differentially inhibited by acarbose. Instead, we discovered that although acarbose primarily targets the Sus periplasmic GH97 enzymes in both organisms, the drug affects starch processing at multiple other points. Acarbose competes for transport through the TonB-dependent SusC proteins and binds to the Sus transcriptional regulators. Furthermore, Bo expresses a non-Sus GH97 (BoGH97D) when grown in starch with acarbose. The Bt homolog, BtGH97H, is not expressed in the same conditions, nor can overexpression of BoGH97D complement the Bt growth inhibition in the presence of acarbose. This work informs us about unexpected complexities of Sus function and regulation in Bacteroides, including variation between related species. Furthermore, this indicates that the gut microbiome may be a source of variable response to acarbose treatment for diabetes. IMPORTANCE Acarbose is a type 2 diabetes medication that works primarily by stopping starch breakdown into glucose in the small intestine. This is accomplished by the inhibition of host enzymes, leading to better blood sugar control via reduced ability to derive glucose from dietary starches. The drug and undigested starch travel to the large intestine where acarbose interferes with the ability of some bacteria to grow on starch. However, little is known about how gut bacteria interact with acarbose, including microbes that can use starch as a carbon source. Here, we show that two gut species, Bacteroides ovatus (Bo) and Bacteroides thetaiotaomicron (Bt), respond differently to acarbose: Bt growth is inhibited by acarbose, while Bo growth is less affected. We reveal a complex set of mechanisms involving differences in starch import and sensing behind the different Bo and Bt responses. This indicates the gut microbiome may be a source of variable response to acarbose treatment for diabetes via complex mechanisms in common gut microbes. Acarbose is a type 2 diabetes medication that works primarily by stopping starch breakdown into glucose in the small intestine. This is accomplished by the inhibition of host enzymes, leading to better blood sugar control via reduced ability to derive glucose from dietary starches. The drug and undigested starch travel to the large intestine where acarbose interferes with the ability of some bacteria to grow on starch. However, little is known about how gut bacteria interact with acarbose, including microbes that can use starch as a carbon source. Here, we show that two gut species, Bacteroides ovatus (Bo) and Bacteroides thetaiotaomicron (Bt), respond differently to acarbose: Bt growth is inhibited by acarbose, while Bo growth is less affected. We reveal a complex set of mechanisms involving differences in starch import and sensing behind the different Bo and Bt responses. This indicates the gut microbiome may be a source of variable response to acarbose treatment for diabetes via complex mechanisms in common gut microbes.

The effect of acarbose on the gut microbiota: an evidence-based review

Type of study: literature review

Number of citations: 1

Year: 2021

Authors: Xianhe Zheng, Zhong-rong Zhang, Jiangchuan Xie

Journal: Frontiers in Medical Science Research

Journal ranking: brak

Key takeaways: Acabose interacts with gut flora, improving medicine efficacy and patient experience by regulating it, and potentially treating and preventing other diseases by targeting gut flora.

Abstract: Acabose is wildly used in various disease treatments and could interact with the gut flora, while the gut flora plays a significant role in human body. This means that acarbose is able to be utilized to improve the efficacy and patient experience by measuring and regulating intestinal flora to achieve precise medicine intake. Moreover, it is also capable to be employed for treating and preventing more other diseases by targeting the gut flora to open up new uses. Based on this hypothesis, we summarized the reasons, methods and results of the interactions between acarbose and intestinal flora, as well as ways for health promotion according to existing experimental results and literature reviews.

Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine.

Type of study: non-rct experimental

Number of citations: 26

Year: 2001

Authors: H. Luo, L. F. Wang, T. Imoto, Y. Hiji

Journal: World journal of gastroenterology

Journal ranking: Q1

Key takeaways: Combining acarbose and gymnemic acid improves maltose absorption inhibition in the small intestine, potentially improving diabetic care.

Abstract: AIM To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P <0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION There are augmented effects of acarbose and GA,which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination.

Pharmacodynamic comparison of acarbose tablets in Chinese healthy volunteers under chewing and swallowing conditions

Type of study: non-rct experimental

Number of citations: 0

Year: 2021

Authors: Wei Ji, Shaomei Yang, Wenyu Zhang, Zhongliang Sun, Qing Wen, K. He

Journal: Journal of Clinical Pharmacy and Therapeutics

Journal ranking: Q2

Key takeaways: Acarbose tablets effectively block glucose absorption in the intestine when swallowed or chewed and swallowed, with no significant difference in pharmacodynamic effects between the two administration routes.

Abstract: Acarbose can efficiently block glucose absorption in the intestine as an alpha‐glucosidase inhibitor. It is currently manufactured in several oral dosage forms, with the most common types being tablets and chewable tablets. The acarbose tablet (Glucobay®, 50 mg, Bayer) package insert gives instructions for either directly swallowing or chewing then swallowing. This study compared the pharmacodynamic effects of a single formulation of acarbose tablets under these two different administration routes.

Effects of beano on the tolerability and pharmacodynamics of acarbose.

Type of study: rct

Number of citations: 18

Year: 1998

Authors: John Lettieri, Bradley Dain

Journal: Clinical therapeutics

Journal ranking: Q1

Key takeaways: Beano can reduce flatulence and potentially interfere with acarbose's glucose-lowering effect, but both treatments significantly lower postprandial serum glucose levels compared to placebo.

Short-term effect of acarbose on specific intestinal disaccharidase activities and hyperglycaemia in CBA diabetic mice.

Type of study: non-rct experimental

Number of citations: 9

Year: 2003

Authors: D. Juretić, S. Bernik, L. Cop, M. Hadzija, R. Petlevski, J. Lukač-bajalo

Journal: Journal of animal physiology and animal nutrition

Journal ranking: Q1

Key takeaways: Acarbose reduces intestinal disaccharidase activities and has an antihyperglycemic effect in diabetic mice, with 100 mg acarbose showing the strongest effect.

Abstract: The purpose of this study was to examine the short-term effects of 75, 100 and 150 mg of acarbose mixed in 100 g standard laboratory chow on specific intestinal disaccharidase activities and on hyperglycaemia in diabetic CBA strain mice on standard diet. The small intestine was excised and divided into three segments, from pylorus to duodenum, and two equal lengths of the jejunum and ileum of control and diabetic mice with or without added acarbose. Specific maltase and sucrase activities were determined using maltose and sucrose as substrates respectively. Increased specific activities of maltase and sucrase were detected in the intestines of CBA mice on standard laboratory diet seven days after alloxan-induced diabetes. Feeding for 7 days with 75, 100 or 150 mg acarbose uniformly mixed in 100 g standard laboratory chow, induced a decrease in the specific maltase and sucrase activities, compared with diabetic mice on standard laboratory diet. Feeding with 75 mg acarbose mixed in 100 g standard laboratory chow caused a statistically significant decrease of maltase in the duodenum and of sucrase in duodenum and jejunum, without a antihyperglycaemic effect. Feeding with 100 or 150 mg caused statistically significant decreases in specific maltase and sucrase activities in duodenum, jejunum and ileum. An antihyperglycaemic effect was observed only in the group of diabetic mice fed with 100 mg acarbose. This indicates that the antihyperglycaemic effect of acarbose involves factors other than these, related only to its inhibitory effect on disaccharidase activities.

The effect of acarbose on inflammatory cytokines and adipokines in adults: a systematic review and meta-analysis of randomized clinical trials

Type of study: meta-analysis

Number of citations: 0

Year: 2024

Authors: Ali Mohammadian, S. Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Niloufar Rasaei, Hossein Bahari, S. Rastgoo, R. Bagheri, Farideh Shiraseb, Omid Asbaghi

Journal: Inflammopharmacology

Journal ranking: Q1

Key takeaways: Acarbose reduces inflammation and increases adiponectin, potentially preventing chronic diseases related to inflammation.

Abstract: BackgroundAlthough a large number of trials have observed an anti-inflammatory property of acarbose, the currently available research remains controversial regarding its beneficial health effects. Hence, the purpose of this study was to examine the effect of acarbose on inflammatory cytokines and adipokines in adults.MethodsPubMed, Web of Science, and Scopus were systematically searched until April 2023 using relevant keywords. The mean difference (MD) of any effect was calculated using a random-effects model. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated via the random-effects model.ResultsThe current meta-analysis of data comprised a total of 19 RCTs. Meta-analysis showed that acarbose significantly decreased tumor necrosis factor-alpha (TNF-α) (weighted mean difference [WMD]) = − 4.16 pg/ml, 95% confidence interval (CI) − 6.58, − 1.74; P = 0.001) while increasing adiponectin (WMD = 0.79 ng/ml, 95% CI 0.02, 1.55; P = 0.044). However, the effects of acarbose on TNF-α concentrations were observed in studies with intervention doses ≥ 300 mg/d (WMD = − 4.09; 95% CI − 7.00, − 1.18; P = 0.006), and the adiponectin concentrations were significantly higher (WMD = 1.03 ng/ml, 95%CI 0.19, 1.87; P = 0.016) in studies in which the duration of intervention was less than 24 weeks. No significant effect was seen for C-reactive protein (CRP; P = 0.134), interleukin-6 (IL-6; P = 0.204), and leptin (P = 0.576).ConclusionAcarbose had beneficial effects on reducing inflammation and increasing adiponectin. In this way, it may prevent the development of chronic diseases related to inflammation. However, more studies are needed.

Acarbose Impairs Gut Bacteroides Growth by Targeting Intracellular GH97 Enzymes

Type of study:

Number of citations: 0

Year: 2024

Authors: Haley A Brown, Adeline L Morris, Nicholas A. Pudlo, Ashley E. Hopkins, E. Martens, Jonathan L. Golob, N. Koropatkin

Journal: bioRxiv

Journal ranking: brak

Key takeaways: Acarbose impairs gut Bacteroides growth by targeting intracellular GH97 enzymes, indicating the gut microbiome may have variable responses to diabetes treatment through complex mechanisms in common gut microbes.

Abstract: Acarbose is a type-2 diabetes medicine that inhibits dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the Bacteroides genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading Bacteroides, Bacteroides ovatus (Bo) and Bacteroides thetaiotaomicron (Bt). Bt growth is severely impaired by acarbose whereas Bo growth is not. The Bacteroides use a starch utilization system (Sus) to grow on starch. We hypothesized that Bo and Bt Sus enzymes are differentially inhibited by acarbose. Instead, we discovered that although acarbose primarily targets the Sus periplasmic GH97 enzymes in both organisms, the drug affects starch processing at multiple other points. Acarbose competes for transport through the Sus beta-barrel proteins and binds to the Sus transcriptional regulators. Further, Bo expresses a non-Sus GH97 (BoGH97D) when grown in starch with acarbose. The Bt homolog, BtGH97H, is not expressed in the same conditions, nor can overexpression of BoGH97D complement the Bt growth inhibition in the presence of acarbose. This work informs us about unexpected complexities of Sus function and regulation in Bacteroides, including variation between related species. Further, this indicates that the gut microbiome may be a source of variable response to acarbose treatment for diabetes. Importance Acarbose is a type 2 diabetes medication that works primarily by stopping starch breakdown into glucose in the small intestine. This is accomplished by inhibition of host enzymes, leading to better blood sugar control via reduced ability to derive glucose from dietary starches. The drug and undigested starch travel to the large intestine where acarbose interferes with the ability of some bacteria to grow on starch. However, little is known about how gut bacteria interact with acarbose, including microbes that can use starch as a carbon source. Here, we show that two gut species, Bacteroides ovatus (Bo) and Bacteroides thetaiotaomicron (Bt), respond differently to acarbose: Bt growth is inhibited by acarbose while Bo growth is not. We reveal a complex set of mechanisms involving differences in starch import and sensing behind the different Bo and Bt responses. This indicates the gut microbiome may be a source of variable response to acarbose treatment for diabetes via complex mechanisms in common gut microbes.

Acarbose Reduces Blood Glucose by Activating miR-10a-5p and miR-664 in Diabetic Rats

Type of study: rct

Number of citations: 51

Year: 2013

Authors: Qian Zhang, Xinhua Xiao, Ming Li, Wen-hui Li, Miao Yu, Huabing Zhang, Zhixin Wang, H. Xiang

Journal: PLoS ONE

Journal ranking: Q1

Key takeaways: Acarbose improves blood glucose in diabetic rats by activating microRNAs in the intestinal epithelium, reducing proinflammatory factors and promoting glucose metabolism.

Abstract: MicroRNAs (miRNAs) are non-coding RNA molecules involved in the post-transcriptional regulation of a large number of genes, including those involved in glucose metabolism. Acarbose is an α-glucosidase inhibitor that improves glycemic control by decreasing the intestinal absorption of glucose, thereby decreasing the elevation of postprandial blood glucose. However, acarbose is poorly absorbed into the blood stream from the gut. Therefore, the exact mechanisms by which acarbose affects glucose metabolism are unclear. This study investigated the effect of acarbose on glucose metabolism in diabetic rats and tested the hypothesis that acarbose acts directly through miRNA-regulated expression in the intestinal epithelium. Rats were divided into four groups: a control group, a diabetic group (DM), a low dose of acarbose group (AcarL) and a high dose of acarbose group (AcarH). Ileum samples were analyzed using miRCURY LNA™ microRNA Array, qPCR and immunohistochemistry. We found that 8-week treatment with acarbose significantly decreased fasting blood glucose. Oral glucose tolerance tests (OGTT) showed that blood glucose was significantly reduced in the AcarL and AcarH groups at 30 min, 60 min and 120 min after oral glucose administration. We found that miR-151*, miR-10a-5p, miR-205, miR-17-5p, miR-145 and miR-664 were up-regulated in the AcarH group, while miR-541 and miR-135b were down-regulated. Through target gene analysis, real time PCR and immunohistochemistry verification, we found that these miRNAs suppressed the expression of proinflammatory cytokines [IL6 (interleukin 6) and TNF (tumor necrosis factor)] and mitogen activated protein kinase 1 (MAPK1). Our data suggest that acarbose can improve blood glucose in diabetic rats through the MAPK pathway and can down-regulate proinflammatory factors by activating miR-10a-5p and miR-664 in the ileum.

Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats

Type of study: rct

Number of citations: 69

Year: 2019

Authors: Minchun Zhang, R. Feng, Meihong Yang, Cheng Qian, Z. Wang, Wei Liu, Jing Ma

Journal: BMJ Open Diabetes Research & Care

Journal ranking: Q1

Key takeaways: Metformin, acarbose, and sitagliptin all lower blood glucose levels, but acarbose selectively increases beneficial bacteria in the gut, suggesting potential for further improvement with probiotics.

Abstract: Objective Recent studies have demonstrated that gut microbiota was closely related to metabolic disorders such as type 2 diabetes. Oral antidiabetic medications including metformin, acarbose and sitagliptin lowered blood glucose levels via acting on the gastrointestinal tract. The aim of the study was to observe the comparisons among those medications on gut microbiota composition. Research design and methods Zucker diabetic fatty rats (n=32) were randomly divided into four groups, and had respectively gastric administration of normal saline (control), metformin (215.15 mg/kg/day), acarbose (32.27 mg/kg/day), or sitagliptin (10.76 mg/kg/day) for 4 weeks. Blood glucose levels were measured during an intragastric starch tolerance test after the treatments. 16S rRNA gene sequencing was used to access the microbiota in the fecal samples. Results Metformin, acarbose, and sitagliptin monotherapy effectively decreased fasting and postprandial blood glucose levels (p<0.001). Acarbose group displayed specific cluster and enterotype mainly composed by Ruminococcus 2 while Lactobacillus was the dominant bacterium in the enterotype of the other three groups. The relative abundance of genera Ruminococcus 2 and Bifidobacterium was dramatically higher in acarbose group. Metformin and sitagliptin increased the relative abundance of genus Lactobacillus. Metagenomic prediction showed that the functional profiles of carbohydrate metabolism were enriched in acarbose group. Conclusions Metformin, acarbose and sitagliptin exerted different effects on the composition of gut microbiota and selectively increased the beneficial bacteria. Supplementation with specific probiotics may further improve the hypoglycemic effects of the antidiabetic drugs.

Acarbose related diarrhea: increased butyrate upregulates prostaglandin E

Type of study:

Number of citations: 35

Year: 2002

Authors: R. Kast

Journal: Inflammation Research

Journal ranking: Q1

Key takeaways: Acarbose may cause diarrhea and colitis due to increased butyrate in the colon, which may lead to water and electrolyte loss.

Abstract: The alpha-glucosidase inhibitor acarbose is a drug used to treat type II diabetes mellitus. It occasionally causes diarrhea. Acarbose related colitis has been reported. This note explains how such side effects may occur. Because of small intestine alpha-glucosidase inhibition, increased starch reaches the colon. Increased colonic starch allows the flora to generate increased butyrate. Absorbed butyrate causes up-regulation of prostaglandin E series production and the latter generates water and electrolyte loss. A colitis results when this acarbose driven process is extreme. Acarbose should be avoided in pregnancy until above can be disproved due to teratogenic and labor inducing potential of prostaglandin E. A theoretical reason for avoiding acarbose in Crohn's disease is presented. Despite these considerations, acarbose remains a safe medicine and may even have salutary intestinal consequences stemming from the same physiology as outlined here.

Acarbose: an alpha-glucosidase inhibitor.

Type of study: literature review

Number of citations: 146

Year: 1996

Authors: Anne E. Martin, P. A. Montgomery

Journal: American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists

Journal ranking: Q1

Key takeaways: Acarbose effectively improves metabolic control in non-insulin-dependent diabetes mellitus patients, with potential for first-line treatment or combination therapy.

Abstract: The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of acarbose, a new antidiabetic agent, are reviewed. Acarbose reversibly inhibits intestinal alpha-glucosidases, enzymes responsible for the metabolism of complex carbohydrates into absorbable monosaccharide units. This action results in a diminished and delayed rise in blood glucose following a meal, resulting in a reduction in post-prandial hyperglycemia, area under the glucose concentration-time curve, and glycosylated hemoglobin. Other effects include a reduction in postprandial insulin and variable changes in plasma lipid concentrations. In placebo-controlled trials, acarbose caused significant improvements in glycemic control indicators, including glycosylated hemoglobin. Acarbose has demonstrated additional glycemic control when added to other antidiabetic therapies, including sulfonylureas and insulin. Efficacy of acarbose appears to be comparable to or slightly less than that of sulfonylureas or metformin, although it has not been compared with maximal dose of these agents. The most commonly reported adverse drug reactions with acarbose are abdominal pain, diarrhea, and flatulence, which tend to lessen with time. Acarbose may affect the bioavailability of metformin and may be less effective when used in conjunction with intestinal adsorbents and digestive enzyme preparations. Concurrent use with hypoglycemic agents (sulfonylureas and insulin) may cause an increased frequency of hypoglycemia. Acarbose should not be used in individuals with certain intestinal disorders, including inflammatory bowel disease. The dosage should start at 25 mg one to three times daily given with the first bite of each main meal and should be adjusted to a maximum of 50 mg three times daily for patients weighing up to 60 kg or 100 mg three times daily for heavier patients. Acarbose may be considered for first-line antidiabetic therapy in certain patients and may be useful as combination therapy in selected instances. Acarbose is efficacious in improving metabolic control in non-insulin-dependent diabetes mellitus. Further evaluation of its effects on the long-term complications of diabetes is needed.

Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti‐hyperglycaemic effect

Type of study: non-rct experimental

Number of citations: 80

Year: 1998

Authors: L. Ranganath, F. Norris, L. M. Morgan, Juliet Wright, Vincent Marks

Journal: Diabetic Medicine

Journal ranking: Q1

Key takeaways: Acarbose delays gastric emptying, contributing to its anti-hyperglycemic effect, potentially due to increased release of glucagon-like peptide-1 (7-36)amide (GLP-1).

Abstract: The therapeutic effect of acarbose is generally attributed to inhibition of amylase and brush border glucosidases and consequent impaired digestion and absorption of carbohydrates. We have investigated the possibility that acarbose may also influence the rate of gastric emptying by comparing plasma glucose and gastrointestinal hormone responses to an oral sucrose load with and without acarbose in 11 healthy subjects. Gastric emptying was assessed indirectly by measuring circulating paracetamol concentrations following administration of paracetamol along with the sucrose load. Peak plasma glucose, insulin, and glucose‐dependent insulinotropic polypeptide (GIP) responses were reduced when sucrose was given with acarbose. There was a significant reduction in post‐sucrose paracetamol levels with acarbose suggestive of a significant delay in gastric emptying. The failure of acarbose to induce change in circulating paracetamol concentrations until after 60 min is indicative of a delay in gastric emptying rather than an osmotic malabsorption. The exaggerated and sustained release of glucagon‐like peptide‐1 (7‐36)amide (GLP‐1) seen when sucrose was given with acarbose may play a part in the inhibition of gastric emptying. This study indicates that a significant delay in gastric emptying may be an added mechanism contributing to the therapeutic effect of acarbose. © 1998 John Wiley & Sons, Ltd.

Habitual Dietary Intake Affects the Altered Pattern of Gut Microbiome by Acarbose in Patients with Type 2 Diabetes

Type of study: non-rct experimental

Number of citations: 25

Year: 2021

Authors: Fumie Takewaki, Hanako Nakajima, D. Takewaki, Y. Hashimoto, Saori Majima, Hiroshi Okada, Takafumi Senmaru, Emi Ushigome, M. Hamaguchi, M. Yamazaki, Yoshiki Tanaka, Shunji Nakajima, H. Ohno, M. Fukui

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Acarbose alters gut microbiome composition in Japanese patients with type 2 diabetes, potentially linked to their habitual dietary intake.

Abstract: The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.

Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice.

Type of study: non-rct experimental

Number of citations: 22

Year: 2018

Authors: Guojian Xu, Lei Cai, Yiliang Ni, Shi-Yi Tian, Ying Lu, Li-Na Wang, Lian-Lian Chen, Wen-ya Ma, Shaoping Deng

Journal: Biological & pharmaceutical bulletin

Journal ranking: Q2

Key takeaways: Voglibose treatment in mice leads to higher concentrations of beneficial short-chain fatty acids, suggesting lower inflammation compared to acarbose treatment.

Abstract: Acarbose and voglibose are the most widely used diabetes drugs as glycosidase inhibitors. In this study, the use of these two inhibitors significantly increased the content of starch in large intestine, and altered the concentration of short-chain fatty acids (SCFAs) by affecting the intestinal microbiota. However, there are some differences in the intestinal microbiome of the two groups of mice, mainly in bacteria such as Bacteroidaceae bacteroides and Desulfovibrionaceae desulfovibrio. The productions of acetate and propionate in caecum in voglibose group were significantly higher than those in acarbose group and two kinds of glycosidase inhibitors were close in the production of butyrate in caecum. The Tax4Fun analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data indicated that different productions of acetate and propionate between acarbose group and voglibose group may be related to 2-oxoisovalerate dehydrogenase and pyruvate oxidase. In addition, in-vitro experiments suggested that voglibose had less effect on epithelial cells than acarbose after direct stimulation. According to the recent researches of SCFAs produced by intestinal microbiota, our comparative study shown higher concentration of these beneficial fatty acids in the lumen of voglibose-treated mice, which implied a lower level of inflammation.

The effect of additional acarbose on metformin-associated artificially high 18F-Fluorodeoxyglucose uptake in positron emission tomography/computed tomography

Type of study: non-rct observational study

Number of citations: 1

Year: 2022

Authors: E. Urhan, Emre Temizer, Z. Karaca, U. Abdulrezzak, Canan Sehit Kara, A. Hacıoğlu, K. Unluhizarci

Journal: Acta Diabetologica

Journal ranking: Q1

Key takeaways: Adding acarbose to metformin therapy decreases artificially high FDG uptake in the colon, potentially offering an alternative recommendation to discontinuing metformin for patients undergoing PET/CT imaging.

Abstract: AimMetformin causes diffuse and intense fluorodeoxyglucose (FDG) uptake more frequently in the colon and less frequently in the small intestine. In this study, we aimed to investigate the effect of simultaneous use of acarbose and metformin on FDG uptake in positron emission tomography/computed tomography (PET/CT), which has not been investigated previously. MethodsTotally 145 patients with a median age of 65 years (range: 18–80 years), who underwent FDG PET/CT in the Department of Nuclear Medicine of Erciyes University Medical School between 2018 and 2021, were involved in the study. The patients undergoing PET/CT were categorized as metformin plus acarbose users (group MA), metformin users (group M), and control subjects without diabetes (group C). The maximum and mean standard uptake values (SUVmax and SUVmean) of FDG uptake of the all intestine segments were measured separately.ResultsThe number of participants in each group was 35, 51 and 59 in group MA, group M and group C, respectively. The FDG uptake of all intestine was significantly higher in group MA and group M than in group C. The FDG uptake of ascending, transverse, descending, and sigmoid colon was significantly lower in group MA than in group M. The FDG uptake of the small intestine was not different between group MA and group M. The FDG uptake of the rectum was lower in group MA than group M and it was significant for SUVmean, but not significant for SUVmax. ConclusionThe addition of acarbose to metformin therapy decreased SUV and artificially high FDG uptake in the colon and may be an alternative recommendation to discontinuing metformin in patients going to PET/CT imaging.

Effect of starch malabsorption on colonic function and metabolism in humans.

Type of study: rct

Number of citations: 74

Year: 1988

Authors: Wolfgang Scheppach, C. Fabian, F. Ahrens, M. Spengler, H. Kasper

Journal: Gastroenterology

Journal ranking: Q1

Key takeaways: Acarbose stimulates carbohydrate fermentation in the colon, potentially impacting colonic and other diseases.

Acarbose improves health and lifespan in aging HET3 mice

Type of study: non-rct experimental

Number of citations: 102

Year: 2019

Authors: D. Harrison, R. Strong, S. Alavez, C. M. Astle, J. DiGiovanni, Elizabeth Fernandez, K. Flurkey, M. Garratt, J. Gelfond, M. Javors, M. Levi, G. Lithgow, F. Macchiarini, James F. Nelson, Stacey J Sukoff Rizzo, T. Slaga, T. Stearns, J. Wilkinson, Richard A. Miller

Journal: Aging Cell

Journal ranking: Q1

Key takeaways: Acarbose, a drug that blocks postprandial glucose spikes, increases mouse lifespan and improves health in aging mice, with larger effects in males.

Abstract: To follow‐up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log‐rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%–11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2‐(2‐hydroxyphenyl) benzothiazole (HBX), and INT‐767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose‐control drugs in humans.

Acarbose potentially binds to the type I peptide deformylase catalytic site and inhibits bacterial growth: An in silico and in vitro study.

Type of study: non-rct in vitro

Number of citations: 1

Year: 2022

Authors: Shashank Kumar, Ashutosh Kumar Singh, K. S. Prajapati

Journal: Current pharmaceutical design

Journal ranking: Q2

Key takeaways: Acarbose shows potential antibacterial activity by binding to the E. coli peptide deformylase catalytic site and inhibiting bacterial growth in vitro.

Abstract: BACKGROUND In bacteria, peptide deformylase (PDF), a metalloenzyme, removes N-formyl methionine from a nascent protein, which is a critical step in the protein maturation process. The enzyme is ubiquitously present in bacteria and possesses therapeutic target potential. Acarbose, an FDA-approved antidiabetic drug, is an alpha-glucosidase inhibitor of microbial origin. Clinical studies indicate that acarbose administration in humans can alter gut microbiota. As per the best of our knowledge, the antibacterial potential of acarbose has not been reported. OBJECTIVE The present study aimed to check the binding ability of acarbose to the catalytic site of E. coli PDF and assess its in vitro antibacterial activity. METHODS Molecular docking, molecular dynamic (MD) simulation, and MM-PBSA experiments were performed to study the binding potential of the catalytic site, and a disc diffusion assay was also employed to assess the antibacterial potential of acarbose. RESULTS Acarbose was found to form a hydrogen bond and interact with the metal ion present at the catalytic site. The test compound showed a better docking score in comparison to the standard inhibitor of PDF. MD simulation results showed energetically stable acarbose-PDF complex formation in terms of RMSD, RMSF, Rg, SASA, and hydrogen bond formation throughout the simulation period compared to the actinonin-PDF complex. Furthermore, MM-PBSA calculations showed better binding free energy (∆G) of acarbose PDF than the actinonin-PDF complex. Moreover, acarbose showed in vitro antibacterial activity. CONCLUSION Acarbose forms conformational and thermodynamically stable interaction with the E. coli peptide deformylase catalytic site. Results of the present work necessitate in-depth antimicrobial potential studies on the effect of acarbose on drug resistance and nonresistant bacteria.

A comparative study of acarbose, vildagliptin and saxagliptin intended for better efficacy and safety on type 2 diabetes mellitus treatment.

Type of study: non-rct experimental

Number of citations: 19

Year: 2021

Authors: Zhongchao Wang, Jing Wang, Jianxia Hu, Ying Chen, B. Dong, Yangang Wang

Journal: Life sciences

Journal ranking: Q1

Key takeaways: Acarbose, vildagliptin, and saxagliptin effectively reduce HbA1c levels and affect intestinal flora distribution in type 2 diabetes patients, with acarbose and vildagliptin showing less adverse reactions than

Fate and effects of the alpha-glucosidase inhibitor acarbose in humans. An intestinal slow-marker perfusion study.

Type of study: rct

Number of citations: 17

Year: 1988

Authors: H. Ruppin, J. Hagel, W. Feuerbach, H. Schutt, J. Pichl, I. Hillebrand, S. Bloom, W. Domschke

Journal: Gastroenterology

Journal ranking: Q1

Key takeaways: Acarbose effectively reduces postprandial blood glucose levels by inhibiting carbohydrate digestion, with higher ileal loads and lower postprandial plasma concentrations compared to placebo.

Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies.

Type of study: meta-analysis

Number of citations: 643

Year: 2004

Authors: M. Hanefeld, M. Çağatay, T. Petrowitsch, D. Neuser, D. Petzinna, M. Rupp

Journal: European heart journal

Journal ranking: Q1

Key takeaways: Acarbose treatment significantly reduces the risk of myocardial infarction and cardiovascular events in type 2 diabetic patients, while improving glycemic control, triglyceride levels, body weight, and systolic blood pressure.

Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes

Type of study:

Number of citations: 173

Year: 2015

Authors: J. DiNicolantonio, J. Bhutani, J. O’Keefe

Journal: Open Heart

Journal ranking: Q1

Key takeaways: Acarbose is a safe and effective oral glucose-lowering drug for treating prediabetes and diabetes, with potential benefits for cardiovascular outcomes.

Abstract: α-Glucosidase inhibitors (AGIs) are a class of oral glucose-lowering drugs used exclusively for treatment or prevention of type 2 diabetes mellitus. AGIs act by altering the intestinal absorption of carbohydrates through inhibition of their conversion into simple sugars (monosaccharides) and thus decrease the bioavailability of carbohydrates in the body, significantly lowering blood glucose levels. The three AGIs used in clinical practice are acarbose, voglibose and miglitol. This review will focus on the cardiovascular properties of acarbose. The current available data suggest that AGIs (particularly acarbose) may be safe and effective for the treatment of prediabetes and diabetes.

Protective effects of acarbose against vascular endothelial dysfunction through inhibiting Nox4/NLRP3 inflammasome pathway in diabetic rats.

Type of study: non-rct experimental

Number of citations: 42

Year: 2019

Authors: Xiaoxue Li, S. Ling, M. Hu, Yu Ma, Yuan Li, Pei-Lin Huang

Journal: Free radical biology & medicine

Journal ranking: Q1

Key takeaways: Acarbose protects against vascular endothelial dysfunction in type 2 diabetes by inhibiting NLRP3 inflammasome and reducing vascular hyperpermeability in diabetic rats.

The effects of acarbose treatment on cardiovascular risk factors in impaired glucose tolerance and diabetic patients: a systematic review and dose–response meta-analysis of randomized clinical trials

Type of study: meta-analysis

Number of citations: 3

Year: 2023

Authors: Mohammad Zamani, Mahlagha Nikbaf-Shandiz, Yasaman Aali, Niloufar Rasaei, M. Zarei, Farideh Shiraseb, Omid Asbaghi

Journal: Frontiers in Nutrition

Journal ranking: Q1

Key takeaways: Acarbose treatment significantly reduces cardiovascular risk factors in impaired glucose tolerance, type 2 diabetes, and type 1 diabetes patients, with a dose-dependent effect on blood glucose levels.

Abstract: Acarbose (ACB) seems to be an effective drug in the management of cardiovascular risk factors. However, no previous meta-analysis of randomized controlled trials (RCTs) has been done to evaluate the effects of ACB on cardiovascular risk factors on impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2D), and type 1 diabetes mellitus (T1D). We comprehensively searched electronic databases including Scopus, Web of Science, and PubMed for RCTs for related keywords up to September 2022. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI). The pooled analysis demonstrated that ACB treatment had a significant effect on fasting blood glucose (FBG) (WMD = −3.55 mg/dL; 95%CI: −6.29, −0.81; p = 0.011), fasting insulin (WMD = −6.73 pmoL/L; 95%CI: −10.37, −3.10; p < 0.001), HbA1c [WMD = −0.32%; 95%CI: −0.45, −0.20; p < 0.001], body weight (WMD = −1.25 kg; 95%CI: −1.79, −0.75; p < 0.001), body mass index (BMI) (WMD = −0.64 kg/m2; 95%CI: −0.92, −0.37; p < 0.001), tumor necrosis factor-alpha (TNF-α) (WMD = −2.70 pg/mL, 95%CI: −5.25, −0.16; p = 0.037), leptin (WMD = −1.58 ng/mL; 95%CI: −2.82, −0.35; p = 0.012), alanine transaminase (ALT) (WMD = 0.71 U/L; 95%CI: −0.31, 1.85; p = 0.164), triglyceride (TG) (WMD = −13.89 mg/dL; 95%CI: −20.69, −7.09; p < 0.001), total cholesterol (TC) (WMD = −2.26 mg/dL; 95%CI: −4.18, −0.34; p = 0.021), systolic blood pressure (SBP) (WMD = −1.29 mmHg; 95%CI: −2.44, −0.15; p = 0.027), and diastolic blood pressure (DBP) (WMD = 0.02 mmHg; 95%CI: −0.41, 0.45; p = 0.925) in an intervention group, compared with a placebo group. The non-linear dose–response analysis showed that ACB reduces the TC in trial duration by >50 weeks, and 180 mg/day is more effective for the decrement of CRP. ACB can improve lipid profiles, glycemic indices, anthropometric indices, and inflammatory markers in T2D, T1D, and IGT patients.

The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24)

Type of study: non-rct observational study

Number of citations: 9

Year: 2021

Authors: Xue-Lian Zhang, S. Yuan, Gang Wan, Ming-Xia Yuan, Guang-Ran Yang, H. Fu, Liang-xiang Zhu, Jian-dong Zhang, Yu-ling Li, Da-yong Gao, Xue-li Cui, Zi-ming Wang, Rongrong Xie, Ying-jun Chen

Journal: Scientific Reports

Journal ranking: Q1

Key takeaways: Acarbose therapy significantly reduces myocardial infarction and all-cause death in type 2 diabetes patients over a 10-year follow-up period.

Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology

Type of study: non-rct experimental

Number of citations: 22

Year: 2020

Authors: Jonathan J. Herrera, Sean Louzon, Kaitlyn Pifer, Danielle C. Leander, Gennifer E. Merrihew, Jea-Hoo Park, Kate Szczesniak, Jeremy A. Whitson, J. Wilkinson, O. Fiehn, M. MacCoss, S. Day, Richard A. Miller, M. Garratt

Journal: JCI Insight

Journal ranking: Q1

Key takeaways: Acarbose, a type 2 diabetes drug, has broad-ranging antiaging effects in multiple tissues, potentially improving physical function and lipid biology in older adults.

Abstract: With an expanding aging population burdened with comorbidities, there is considerable interest in treatments that optimize health in later life. Acarbose (ACA), a drug used clinically to treat type 2 diabetes mellitus (T2DM), can extend mouse life span with greater effect in males than in females. Using a genetically heterogeneous mouse model, we tested the ability of ACA to ameliorate functional, pathological, and biochemical changes that occur during aging, and we determined which of the effects of age and drug were sex dependent. In both sexes, ACA prevented age-dependent loss of body mass, in addition to improving balance/coordination on an accelerating rotarod, rotarod endurance, and grip strength test. Age-related cardiac hypertrophy was seen only in male mice, and this male-specific aging effect was attenuated by ACA. ACA-sensitive cardiac changes were associated with reduced activation of cardiac growth–promoting pathways and increased abundance of peroxisomal proteins involved in lipid metabolism. ACA further ameliorated age-associated changes in cardiac lipid species, particularly lysophospholipids — changes that have previously been associated with aging, cardiac dysfunction, and cardiovascular disease in humans. In the liver, ACA had pronounced effects on lipid handling in both sexes, reducing hepatic lipidosis during aging and shifting the liver lipidome in adulthood, particularly favoring reduced triglyceride (TAG) accumulation. Our results demonstrate that ACA, already in clinical use for T2DM, has broad-ranging antiaging effects in multiple tissues, and it may have the potential to increase physical function and alter lipid biology to preserve or improve health at older ages.

On the potential of acarbose to reduce cardiovascular disease

Type of study:

Number of citations: 50

Year: 2014

Authors: E. Standl, M. Theodorakis, M. Erbach, O. Schnell, J. Tuomilehto

Journal: Cardiovascular Diabetology

Journal ranking: Q1

Key takeaways: Acarbose shows potential in reducing cardiovascular disease risk in diabetic patients, with acceptable side effects and potential benefits in patients with coronary heart disease and impaired glucose tolerance.

Abstract: In the emerging landscape of cardiovascular (CV) outcome trials evaluating the effects of blood glucose lowering drugs in individuals with type 2 diabetes, it is becoming increasingly apparent that since the promising signals coming from the United Kingdom Prospective Diabetes Study (UKPDS) no unequivocal benefits have been established for any single therapy thus far. There is an unmet need for introducing an effective pharmacological agent which could target both correlates of glycaemic regulation and CV risk factors, to ameliorate the enormous burden of fatal and non-fatal CV events in diabetic patients. Acarbose, like other alpha-glucosidase inhibitors (AGIs), has been proven to be an effective antidiabetic treatment for decades, but the overall significant impact of this class of drugs on modulating CV risk has only recently been appreciated. Accumulating evidence has shown that apart from its multiple effects on primarily postprandial glucose dysmetabolism, a key component of mechanisms linked to increased incidence of CV events, acarbose therapy also associates with a favorable impact on an array of surrogate markers of CV disease. Data stemming from in vitro testing of human cell lines as well as from preliminary trials in diabetic populations, like the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial, have highlighted - though not undisputed - the potential beneficial effects of the drug on CV morbidity. Large scale trials, like the ongoing Acarbose Cardiovascular Evaluation (ACE) trial, aim at conclusively establishing such a positive effect in patients with coronary heart disease and impaired glucose tolerance. In view of its usually acceptable level of side effects that are, if they occur, mostly limited to transient gastrointestinal symptoms, acarbose could well be a strong future player in CV disease secondary prevention. Current discouraging results from many trials of antidiabetic medications to significantly lower CV event rates in diabetic patients, should only draw further attention on alternative glucose lowering agents, among which acarbose is indeed promising.

Synergistic cardioprotective ability of co-administration of Moringa supplemented diets and acarbose in diabetic cardiomyopathy involves attenuation of cholinergic, purinergic, monoaminergic, renin-angiotensin system, and antioxidant pathways.

Type of study: non-rct experimental

Number of citations: 6

Year: 2022

Authors: S. Oyeleye, A. Ademiluyi, Ojo O Raymond, G. Oboh

Journal: Journal of food biochemistry

Journal ranking: Q1

Key takeaways: Co-administration of Moringa leaf/seed supplemented diets and acarbose shows a synergistic effect in managing diabetic cardiomyopathy, improving antioxidant status and modulating biochemicals.

Abstract: One of the major complications of diabetes mellitus (DM) is diabetic cardiomyopathy (DCM) due to the multifaceted therapy involved. Here, we evaluated the combinatorial effect of Moringa leaf (ML) and seed (MS) supplemented diets plus acarbose (ACA) on cardiac acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), adenosine deaminase (ADA), monoamine oxidase (MAO), arginase, angiotensin-I converting enzyme (ACE), and lactate dehydrogenase (LDH) activities, thiobarbituric acid reactive species (TBARS), and thiols levels. The diets and ACA (25 mg/kg) were administered for 14 days. The fasting blood glucose level (FBGL), cardiac AChE, ATPase, ADA, MAO, arginase, ACE, LDH activities, and TBARS and thiol levels were determined. Relative to the normal rats, the biomarkers were significantly increased in DM rats but were suppressed significantly in the diets plus ACA-treated rats while improving antioxidant status, with the 4% Moringa plus ACA proving outstanding compared to individual ML/MS and ACA. In addition, ML-supplemented diets with/without ACA had better effects compared to MS with/without ACA, respectively. In conclusion, the combination of ML/MS supplemented diets and ACA synergistically modulates the tested biochemicals. However, the effect on blood vessels and the nerves that control the heart, stiffness of left ventricular (LV) hypertrophy, fibrosis, cell signaling abnormalities, related gene expression, clinical trials, and echocardiology studies should be further investigated to affirm this claim. PRACTICAL APPLICATIONS: Moringa oleifera has been a vocal appetite in mitigating cardiovascular disease induced by diabetes, but the formulation of a medicinal diet as an ameliorative route of attention to the pathology is fairly addressed, not talking of its combination with the synthetic antidiabetic drug, such as ACA. Based on this experiment, it is imperative to explore such an idea. This research shows that co-administration of moringa leaf/seed formulated diets plus ACA exhibits a synergistic effect in DCM management. However, further research is needed in this field of experiment.

Acarbose: oral antidiabetes drug with additional cardiovascular benefits

Type of study:

Number of citations: 74

Year: 2008

Authors: M. Hanefeld, F. Schaper

Journal: Expert Review of Cardiovascular Therapy

Journal ranking: Q2

Key takeaways: Acarbose effectively lowers HbA1c levels in Type 2 diabetes patients, reduces the incidence of newly diagnosed diabetes, and has beneficial effects on overweight, blood pressure, triglycerides, and inflammation.

Abstract: Acarbose is an α-glucosidase inhibitor acting specifically at the level of postprandial glucose excursion. This compound lowers HbA1c by 0.5–1% in patients with Type 2 diabetes, either drug naive or in combination with other antidiabetic drugs. In those with impaired glucose tolerance (IGT), it reduces the incidence of newly diagnosed diabetes by 36.4%. Furthermore, it has beneficial effects on overweight, reduces blood pressure and triglycerides, and downregulates biomarkers of low-grade inflammation. In the Study To Prevent Non-Insulin-Dependent-Diabetes-Mellitus (STOP-NIDDM) trial, acarbose significantly reduced the progression of intima media thickness, incidence of cardiovascular events and of newly diagnosed hypertension. In a meta-analysis of patients with Type 2 diabetes (MERIA), acarbose intake was associated with a reduction of cardiovascular events by 35%. Acarbose is a very safe drug but in approximately 30% of patients, it can cause gastrointestinal complaints due to its mode of action, which in the majority disappear after 1–2 months. Acarbose is approved for treatment of IGT in 25 countries. It can be given alone or in combination with other oral antidiabetics and insulin. Acarbose is particularly effective in those with IGT and early diabetes and patients with comorbidities of the metabolic syndrome.

Effects of 24-week treatment with acarbose on glucagon-like peptide 1 in newly diagnosed type 2 diabetic patients: a preliminary report

Type of study: non-rct experimental

Number of citations: 55

Year: 2013

Authors: Miaoyan Zheng, Juhong Yang, Chunyan Shan, Hong-tao Zhou, Yan-guang Xu, Ying Wang, Hui-zhu Ren, B. Chang, Li-ming Chen

Journal: Cardiovascular Diabetology

Journal ranking: Q1

Key takeaways: Acarbose treatment for 24 weeks in newly diagnosed type 2 diabetic patients increases GLP-1 levels and nitric oxide levels, potentially contributing to its cardiovascular risk reduction benefits.

Abstract: Treatment with the alpha-glucosidase inhibitor (AGI) acarbose is associated with a significant reduction the risk of cardiovascular events. However, the underlying mechanisms of this effect are unclear. AGIs were recently suggested to participate in stimulating glucagon-like peptide 1 (GLP-1) secretion. We therefore examined the effects of a 24-week treatment of acarbose on endogenous GLP-1, nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and carotid intima-media thickness (CIMT) in newly diagnosed patients with type 2 diabetes (T2D).Blood was drawn from 24 subjects (14 male, 10 female, age: 50.7 ± 7.36 years, BMI: 26.64 ± 3.38 kg/m2, GHbA1c: 7.00 ± 0.74%) with drug-naïve T2D at 0 and 120 min following a standard mixed meal for the measurements of active GLP-1, NO and NOS. The CIMT was measured prior to and following 24 weeks of acarbose monotherapy (mean dose: 268 mg daily).Following 24 weeks of acarbose treatment, both fasting and postprandial plasma GLP-1 levels were increased. In patients with increased postprandial GLP-1 levels, serum NO levels and NOS activities were also significantly increased and were positively related to GLP-1 levels. Although the CIMT was not significantly altered following treatment with acarbose, a decreased CIMT was negatively correlated with increased GLP-1 levels.Twenty-four weeks of acarbose monotherapy in newly diagnosed patients with T2D is associated with significantly increased levels of both fasting and postprandial GLP-1 as well as significantly increased NO levels and NOS activity for those patients in whom postprandial GLP-1 levels were increased. Therefore, the benefits of acarbose on cardiovascular risk may be related to its stimulation of GLP-1 secretion.

Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial.

Type of study: rct

Number of citations: 114

Year: 2006

Authors: J. Chiasson

Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

Journal ranking: Q1

Key takeaways: Acarbose treatment effectively reduces the risk of type 2 diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance.

Abstract: OBJECTIVE To evaluate, in subjects with impaired glucose tolerance (IGT), the effect of acarbose on the incidence of diabetes, hypertension, and cardiovascular disease. METHODS The Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial was an international, multicenter, double-blind, placebo-controlled, randomized investigation, undertaken in 9 participating countries from December 1995 through August 2001. Patients were randomly assigned to receive placebo (N = 715) or acarbose, 100 mg three times a day (N = 714), and underwent follow-up for a mean of 3.3 years. Sixty-one subjects (4%) were excluded from the study because they did not have IGT or had no postrandomization data; thus, 1,368 subjects remained for intent-to-treat analysis. The outcome measures were the development of diabetes based on a single oral glucose tolerance test, the development of hypertension ((3) 140/90 mm Hg), and the development of major cardiovascular events, including coronary heart disease, cardiovascular death, stroke, and peripheral vascular disease. RESULTS Two hundred eleven subjects in the acarbose-treated group and 130 in the placebo group discontinued treatment prematurely; however, they underwent follow-up for assessment of end points. Acarbose treatment resulted in a 25% relative risk reduction in the development of type 2 diabetes (hazards ratio [HR], 0.75; 95% confidence interval [CI], 0.63 to 0.90; P = 0.0015), in a 34% risk reduction in the development of new cases of hypertension (HR, 0.66; 95% CI, 0.49 to 0.89; P = 0.0059), and in a 49% risk reduction in the development of cardiovascular events (HR, 0.51; 95% CI, 0.28 to 0.95; P = 0.03). A post hoc cost-effectiveness analysis done from the Swedish perspective showed that acarbose treatment was likely to be cost-effective in the management of subjects with IGT. CONCLUSION The STOP-NIDDM Trial demonstrated that, in subjects with IGT, acarbose treatment was effective in reducing the risk of type 2 diabetes. It also suggested that it was associated with a reduction in hypertension and cardiovascular disease.

Effects of acarbose on proinsulin and insulin secretion and their potential significance for the intermediary metabolism and cardiovascular system.

Type of study: literature review

Number of citations: 31

Year: 2009

Authors: C. Rosak, G. Mertes

Journal: Current diabetes reviews

Journal ranking: Q2

Key takeaways: Acarbose effectively controls blood glucose levels in type 2 diabetic patients and reduces the risk of cardiovascular disease, while also moderating insulin and proinsulin secretion, potentially reducing cardiovascular mortality risk.

Abstract: The alpha-glucosidase inhibitor acarbose is administered to control blood glucose levels in type 2 diabetic patients and, in several countries, in those with impaired glucose tolerance. The efficacy and safety of the drug has been well established in these patient populations. Acarbose shows no weakening of efficacy in long-term diabetes treatment, reduces the development of type 2 diabetes in those with impaired glucose tolerance, and also appears to reduce the risk of cardiovascular disease. The underlying mechanisms of its effect on the risk of developing macrovascular complications have still to be elucidated. The mode of action of acarbose, which precedes all other metabolic processes involved in blood glucose regulation, inhibits high increases in postprandial blood glucose. Due to this early mode of action, acarbose also modifies insulin and proinsulin secretion which are both involved in ss-cell dysfunction and insulin resistance and may be independent risk factors for cardiovascular mortality. Based on the literature available the present state of knowledge on insulin and proinsulin as risk factors for cardiovascular mortality is reviewed as well as the effect of acarbose on the regulation of the ss-cells as monotherapy and in combination regimens. Possible associated interactions with the cardiovascular system are identified.

Effect of acarbose on cardiovascular events and new-onset diabetes in patients with coronary heart disease and impaired glucose tolerance.

Type of study:

Number of citations: 8

Year: 2019

Authors: Yidong Wei, Wen Xu

Journal: Future cardiology

Journal ranking: Q3

Key takeaways: Acarbose does not reduce the risk of major cardiovascular events, but reduces the risk of new-onset diabetes by 18% in patients with coronary heart disease and impaired glucose tolerance.

Abstract: Many studies indicated postprandial hyperglycemia was closely related to the development of diabetes and the risk of cardiovascular disease. Acarbose was shown to delay the onset of diabetes in people with impaired glucose tolerance that was at low cardiovascular risk. The Acarbose Cardiovascular Evaluation (ACE) trial formally evaluated whether acarbose could reduce the frequency of cardiovascular events in patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of Type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation trial represented that acarbose did not reduce the risk of Major Adverse Cardiovascular Events (MACE), but the risk of new-onset diabetes by 18% for a median of 5.0 years follow-up.

The effect of acarbose on lipid profiles in adults: a systematic review and meta-analysis of randomized clinical trials

Type of study: meta-analysis

Number of citations: 5

Year: 2023

Authors: Mohsen Yousefi, S. Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, S. Rastgoo, Reza Bagher, Alireza Khadem, Farideh Shiraseb, Omid Asbaghi

Journal: BMC Pharmacology & Toxicology

Journal ranking: Q2

Key takeaways: Acarbose can reduce triglyceride and total cholesterol levels in adults, but has no significant effect on LDL or HDL levels.

Abstract: Abstract Purpose Dyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density lipoprotein (HDL), is a major risk factor for cardiovascular diseases (CVD). Several studies have shown the potential of acarbose in improving serum lipid markers. However, there have been conflicting results on the topic in adults. Therefore, a comprehensive systematic review and meta-analysis was conducted to assess the impact of acarbose on lipid profiles. Methods The random-effects approach was used to combine the data, and the results were provided as weighted mean difference (WMD) with 95% confidence intervals (CI). Results Our meta-analysis included a total of 74 studies with a combined sample size of 7046 participants. The results of the analysis showed that acarbose resulted in a reduction in levels of TG (WMD = − 13.43 mg/dl, 95% CI: − 19.20, − 7.67; P &lt; 0.001) and TC (WMD = − 1.93 mg/dl, 95% CI: − 3.71, − 0.15; P = 0.033), but did not affect other lipid markers. When conducting a nonlinear dose-response analysis, we found that acarbose was associated with an increase in levels of HDL (coefficients = 0.50, P = 0.012), with the highest increase observed at a dosage of 400 mg/d. Furthermore, our findings suggested a non-linear relationship between the duration of the intervention and TC (coefficients = − 18.00, P = 0.032), with a decline observed after 50 weeks of treatment. Conclusion The findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.

Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial.

Type of study: rct

Number of citations: 1703

Year: 2003

Authors: J. Chiasson, R. Josse, R. Gomis, M. Hanefeld, A. Karasik, M. Laakso

Journal: JAMA

Journal ranking: brak

Key takeaways: Acarbose treatment reduces the risk of cardiovascular events and hypertension in patients with impaired glucose tolerance, with a major reduction in myocardial infarction.

Abstract: CONTEXT The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns. OBJECTIVE To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an alpha-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT). DESIGN, SETTING, AND PARTICIPANTS International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years. INTERVENTION Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714). MAIN OUTCOME MEASURES The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (> or =140/90 mm Hg). RESULTS Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P =.03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P =.02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P =.006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P =.02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P =.004) associated with acarbose treatment was still statistically significant. CONCLUSION This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

Abstract 18270: Acarbose Attenuates Age-Associated Declines in Motor and Cardiac Function

Type of study:

Number of citations: 0

Year: 2017

Authors: Sean Louzon, Jonathan J. Herrera, Jaime Yob, K. Converso, Richard J. Miller, S. Day

Journal: Circulation

Journal ranking: Q1

Key takeaways: Acarbose, an alpha-glucosidase inhibitor, can extend lifespan and diminish age-related declines in motor and cardiac function in mice.

Abstract: Background: Age is a primary risk factor for chronic conditions including cardiovascular diseases. With inflation in the aged population over the last century, there is a growing need for interventions that directly target aging. Acarbose, an alpha-glucosidase inhibitor, is a promising aging intervention that increases lifespan in male and female mice by 22% and 5%, respectively. Acarbose is an FDA approved anti-diabetic drug with a limited side effect profile. We hypothesized that, in addition to lengthening lifespan, Acarbose would also diminish the effects of aging on motor and cardiac function. Methods and Results: Outbred male and female F1 mice that were a cross of 4 strains were treated with Acarbose (ACA, 1000 ppm) or a control diet from 8 months to 22 months of age. Both groups of aged 22 month old mice were compared to 4 month control mice in motor performance and echocardiography. Grip strength, a strong predictor of all cause and cardiovascular mortality in humans, was reduced with age (0.511 ...

Early or late-life treatment with acarbose or rapamycin improves physical performance and affects cardiac structure in aging mice.

Type of study: non-rct experimental

Number of citations: 10

Year: 2022

Authors: Jonathan J. Herrera, Kaitlyn Pifer, Sean Louzon, Danielle C. Leander, O. Fiehn, S. Day, Richard A. Miller, M. Garratt

Journal: The journals of gerontology. Series A, Biological sciences and medical sciences

Journal ranking: Q1

Key takeaways: Late-life treatment with acarbose or rapamycin improves physical performance and reduces cardiac hypertrophy in aged mice, with some benefits occurring only in males.

Abstract: Pharmacological treatments can extend lifespan in mice. For optimal translation in humans, treatments should improve health during aging, and demonstrate efficacy when started later in life. Acarbose (ACA) and Rapamycin (RAP) extend lifespan in mice when treatment is started early or later in life. Both drugs can also improve some indices of healthy aging, although there has been little systematic study of whether health benefits accrue differently depending on the age at which treatment is started. Here we compare the effects of early (4 month) versus late (16 month) onset ACA or RAP treatment on physical function and cardiac structure in genetically heterogeneous aged mice. ACA or RAP treatment improve rotarod acceleration and endurance capacity compared to controls, with effects that are largely similar in mice starting treatment from early or late in life. Compared to controls, cardiac hypertrophy is reduced by ACA or RAP in both sexes regardless of age treatment onset. ACA has a greater effect on the cardiac lipidome than RAP, and effects of early life treatment are recapitulated by late life treatment. These results indicate that late life treatment with these drugs provide at least some of the benefits of life long treatment, although some of the benefits occur only in males, which could lead to sex differences in health outcomes later in life.

Impact of Acarbose on Incident Diabetes and Regression to Normoglycemia in People With Coronary Heart Disease and Impaired Glucose Tolerance: Insights From the ACE Trial

Type of study: rct

Number of citations: 14

Year: 2020

Authors: H. Gerstein, R. Coleman, Charles A. B. Scott, Shishi Xu, J. Tuomilehto, L. Rydén, R. Holman

Journal: Diabetes Care

Journal ranking: Q1

Key takeaways: Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with impaired glucose tolerance and coronary heart disease.

Abstract: OBJECTIVE We examined the impact of acarbose, an α-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation (ACE) trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD). RESEARCH DESIGN AND METHODS Participants were randomly assigned to acarbose or placebo and followed with four monthly fasting plasma glucose (FPG) tests and annual oral glucose tolerance tests. Incident diabetes was defined as two successive diagnostic FPG levels ≥7 mmol/L or 2-h plasma glucose (PG) levels ≥11.1 mmol/L while taking study medication or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG <6.1 mmol/L and 2-h PG <7.8 mmol/L. Intention-to-treat and on-treatment analyses were conducted using Poisson regression models, overall and for subgroups (age, sex, CHD type, HbA1c, FPG, 2-h PG, BMI, estimated glomerular filtration rate, for IGT alone, for IGT + impaired fasting glucose, and for use of thiazides, ACE inhibitors [ACEis]/angiotensin receptor blockers [ARBs], β-blockers, calcium channel blockers, or statins). RESULTS Incident diabetes was less frequent with acarbose compared with placebo (3.2 and 3.8 per 100 person-years, respectively; rate ratio 0.82 [95% CI 0.71, 0.94], P = 0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose compared with placebo (16.3 and 14.1 per 100 person-years, respectively; 1.16 [1.08, 1.25], P < 0.0001). This effect was greater in participants not taking an ACEi or ARB (1.36 [1.21, 1.53], Pinteraction = 0.0006). The likelihood of remaining in normoglycemic regression did not differ between the acarbose and placebo groups (P = 0.41). CONCLUSIONS Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD.

The effect of acarbose treatment on anthropometric indices in adults: a systematic review and meta-analysis of randomized clinical trials

Type of study: meta-analysis

Number of citations: 2

Year: 2024

Authors: Elnaz Golalipour, Dorsa Hosseininasab, Mahlagha Nikbaf-Shandiz, Niloufar Rasaei, Hossein Bahari, Mahya Mehri Hajmir, S. Rastgoo, Farideh Shiraseb, Omid Asbaghi

Journal: Clinical Nutrition Open Science

Journal ranking: Q3

Key takeaways: Acarbose treatment significantly decreased body weight, BMI, and waist circumference in adults.

The Effects of Acarbose on Non-Diabetic Overweight and Obese Patients: A Meta-Analysis

Type of study: meta-analysis

Number of citations: 12

Year: 2021

Authors: Ai-Qing Yu, Jiong Le, Wen-Tao Huang, Bin Li, Huimin Liang, Qun Wang, Yu-Ting Liu, Charlotte Young, Meilan Zhang, Shu-Lan Qin

Journal: Advances in Therapy

Journal ranking: Q1

Key takeaways: Acarbose monotherapy effectively reduces triglyceride levels in obese or overweight patients without causing hypoglycemia, with mild side effects.

Abstract: IntroductionThis systematic review aims to verify the efficacy of acarbose monotherapy in treating obese or overweight patients without diabetes.MethodsIn the study, we conducted a systematic search of the Pub-Med, EMBASE, Cochrane and Science Citation Index Expanded databases in search of clinical trials on acarbose treatment, overweight and obesity. The crucial inclusion criteria were as follows: (1) patients were diagnosed as overweight or obese (BMI ≥ 25 kg/m^2); (2) randomized controlled trials (RCTs); (3) patients had undergone acarbose monotherapy or placebo control; (4) acarbose treatment had been carried out for at least 3 months. Exclusion criteria were as follows: (1) patients diagnosed with diabetes mellitus (DM); (2) patients had received a weight loss medication or surgery in the past 3 months; (3) papers not published in English; (4) repeated research results of the same experiment or repeated published documents.ResultsA total of 7 studies involving 132 in the acarbose group and 137 in placebo group, 269 subjects in total, were included in this meta-analysis. From the selected seven papers, we extracted the following clinical parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight (BW), body mass index (BMI), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density cholesterol (HDL) and fasting plasma glucose (FPG). An important finding of our research is that TG was the only significantly reduced parameter in the acarbose group. Weight mean difference (WMD) was − 0.21 (95% CI − 0.33, − 0.09) mmol/l between acarbose (P = 0.0006) and placebo patients. Reduction of BMI was also greater for acarbose than placebo subjects, although the discrepancy was not statistically significant (P = 0.56). Moreover, no hypoglycemia occurred in either the acarbose group or placebo group. A few subjects experienced gastrointestinal reactions, but these were mild and improved over time. Acarbose has no obvious influence on other metabolic indexes.ConclusionAcarbose monotherapy is beneficial in reducing TG levels in obese or overweight patients and will not result in hypoglycemia during medication. The side effects of acarbose are mild.

Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment

Type of study: non-rct experimental

Number of citations: 325

Year: 2017

Authors: Yanyun Gu, Xiaokai Wang, Junhua Li, Yifei Zhang, Huanzi Zhong, Ruixin Liu, Dongya Zhang, Q. Feng, Xiaoyan Xie, Jie Hong, Huahui Ren, Wei Liu, Jing Ma, Q. Su, Hongmei Zhang, Jialin Yang, Xiaolin Wang, Xinjie Zhao, W. Gu, Y. Bi, Yongde Peng, Xiaoqiang Xu, Huihua Xia, Fang Li, Xun Xu, Huanming Yang, Guowang Xu, L. Madsen, K. Kristiansen, G. Ning, Weiqing Wang

Journal: Nature Communications

Journal ranking: Q1

Key takeaways: Acarbose treatment improves metabolic health in type 2 diabetes patients by altering gut microbiota composition and altering bile acid metabolism, with greater improvements observed in those with a high abundance of Bacteroides in their gut microbiota.

Acarbose ameliorates Western diet-induced metabolic and cognitive impairments in the 3xTg mouse model of Alzheimer's disease.

Type of study: non-rct experimental

Number of citations: 2

Year: 2024

Authors: Michelle M Sonsalla, R. Babygirija, Madeline Johnson, Samuel Cai, Mari Cole, Chung-Yang Yeh, Isaac Grunow, Yang Liu, Diana Vertein, Mariah F. Calubag, Michaela E Trautman, Cara L Green, Michael J. Rigby, Luigi Puglielli, Dudley Lamming

Journal: GeroScience

Journal ranking: Q1

Key takeaways: Acarbose may be a promising intervention to prevent, delay, or treat Alzheimer's disease by improving metabolic health and cognitive deficits in mice fed a high-fat, high-sucrose Western diet.

Abstract: Age is the greatest risk factor for Alzheimer’s disease (AD) as well as for other disorders that increase the risk of AD such as diabetes and obesity. There is growing interest in determining if interventions that promote metabolic health can prevent or delay AD. Acarbose is an anti-diabetic drug that not only improves glucose homeostasis, but also extends the lifespan of wild-type mice. Here, we test the hypothesis that acarbose will not only preserve metabolic health, but also slow or prevent AD pathology and cognitive deficits in 3xTg mice, a model of AD, fed either a Control diet or a high-fat, high-sucrose Western diet (WD). We find that acarbose decreases the body weight and adiposity of WD-fed 3xTg mice, increasing energy expenditure while also stimulating food consumption, and improves glycemic control. Both male and female WD-fed 3xTg mice have worsened cognitive deficits than Control-fed mice, and these deficits are ameliorated by acarbose treatment. Molecular and histological analysis of tau and amyloid pathology identified sex-specific effects of acarbose which are uncoupled from the dramatic improvements in cognition in females, suggesting that the benefits of acarbose on AD may be largely driven by improved metabolic health. In conclusion, our results suggest that acarbose may be a promising intervention to prevent, delay, or even treat AD, especially in individuals consuming a WD.

Diabetes medications as potential calorie restriction mimetics—a focus on the alpha-glucosidase inhibitor acarbose

Type of study:

Number of citations: 26

Year: 2020

Authors: Daniel L Smith, R. Orlandella, D. Allison, L. Norian

Journal: GeroScience

Journal ranking: Q1

Key takeaways: Acarbose, an alpha-glucosidase inhibitor, shows potential as a calorie restriction mimetics for healthy aging and longevity extension without requiring food intake reductions.

Abstract: The field of aging research has grown rapidly over the last half-century, with advancement of scientific technologies to interrogate mechanisms underlying the benefit of life-extending interventions like calorie restriction (CR). Coincident with this increase in knowledge has been the rise of obesity and type 2 diabetes (T2D), both associated with increased morbidity and mortality. Given the difficulty in practicing long-term CR, a search for compounds (CR mimetics) which could recapitulate the health and longevity benefits without requiring food intake reductions was proposed. Alpha-glucosidase inhibitors (AGIs) are compounds that function predominantly within the gastrointestinal tract to inhibit α-glucosidase and α-amylase enzymatic digestion of complex carbohydrates, delaying and decreasing monosaccharide uptake from the gut in the treatment of T2D. Acarbose, an AGI, has been shown in pre-clinical models to increase lifespan (greater longevity benefits in males), with decreased body weight gain independent of calorie intake reduction. The CR mimetic benefits of acarbose are further supported by clinical findings beyond T2D including the risk for other age-related diseases (e.g., cancer, cardiovascular). Open questions remain regarding the exclusivity of acarbose relative to other AGIs, potential off-target effects, and combination with other therapies for healthy aging and longevity extension. Given the promising results in pre-clinical models (even in the absence of T2D), a unique mechanism of action and multiple age-related reduced disease risks that have been reported with acarbose, support for clinical trials with acarbose focusing on aging-related outcomes and incorporating biological sex, age at treatment initiation, and T2D-dependence within the design is warranted.

Acarbose reduces body weight irrespective of glycemic control in patients with diabetes: results of a worldwide, non-interventional, observational study data pool.

Type of study: meta-analysis

Number of citations: 29

Year: 2016

Authors: O. Schnell, J. Weng, W. Sheu, H. Watada, S. Kalra, S. Soegondo, N. Yamamoto, R. Rathod, Cheryl Zhang, W. Grzeszczak

Journal: Journal of diabetes and its complications

Journal ranking: Q1

Key takeaways: Acarbose treatment reduces body weight in patients with diabetes regardless of glycemic control status, but is dependent on baseline body weight.

Acarbose in obese patients with polycystic ovarian syndrome: a double-blind, randomized, placebo-controlled study.

Type of study: rct

Number of citations: 67

Year: 2005

Authors: Ivan Araujo Penna, P.R.B. Canella, R. M. Reis, M. D. Sá, R. Ferriani

Journal: Human reproduction

Journal ranking: Q1

Key takeaways: Low-dose acarbose effectively reduces free androgen index, BMI, and SHBG levels, improves hirsutism and menstrual patterns, and is well-tolerated by patients.

Abstract: BACKGROUND The present study assessed the effects of low-dose acarbose on obese patients with polycystic ovarian syndrome (PCOS). METHODS A double-blind placebo-controlled study was conducted on 30 obese hyperinsulinaemic women with PCOS treated with 150 mg/day acarbose or placebo for 6 months. The women were evaluated for hirsutism, menstrual regularity, body mass index (BMI), insulin resistance and glucose tolerance, sex hormone-binding globulin (SHBG), LH, FSH, testosterone and androstenedione, and side-effects. RESULTS The patients in the acarbose group showed a reduction in BMI (35.87 +/- 2.60 versus 33.10 +/- 2.94 kg/m(2)) and in the Ferriman-Gallwey index (8.85 +/- 2.31 versus 8 +/- 1.82), and an increased chance of menstrual regularity (rate = 2.67). SHBG concentration increased (21.01 +/- 7.9 versus 23.85 +/- 7.77 nmol/l) and the free androgen index was reduced (14.81 +/- 9.06 versus 11.48 +/- 6.18). None of these parameters were modified in the placebo group. Mild side-effects occurred in 84% of the patients in the acarbose group and disappeared after the first 3 months. CONCLUSION A low dose of acarbose administered to obese patients with PCOS promotes a reduction in free androgen index and BMI and an increase in SHBG, with improvement of hirsutism and of the menstrual pattern, and is well tolerated by patients.

A systematic review, meta-analysis, dose-response, and meta-regression of the effects of acarbose intake on glycemic markers in adults.

Type of study: meta-analysis

Number of citations: 0

Year: 2023

Authors: Sina Raissi Dehkordi, N. Pahlavani, Mahlagha Nikbaf-Shandiz, R. Bagheri, Niloufar Rasaei, Melika Darzi, S. Rastgoo, Hossein Bahari, Farideh Shiraseb, Omid Asbaghi

Journal: Journal of diabetes and metabolic disorders

Journal ranking: Q2

Key takeaways: Acarbose intake can potentially lead to significant improvements in glycemic parameters by decreasing fasting blood sugar, HbA1c, and insulin levels in adults.

Abstract: PurposePrior research has yielded mixed results regarding the impact of acarbose intake on glycemic markers. To provide a more comprehensive analysis, a systematic review and meta-analysis was performed to compile data from various randomized controlled trials (RCTs) examining the effects of acarbose intake on fasting blood sugar (FBS), insulin, hemoglobin A1C (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) in adults.MethodsTo identify relevant literature up to April 2023, a comprehensive search was conducted on various scholarly databases, including PubMed, Web of Science, and Scopus databases. The effect size of the studies was evaluated using a random-effects model to calculate the weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity between studies was assessed using Cochran’s Q test and I^2.ResultsThis systematic review and meta-analysis included a total of 101 RCTs with a total of 107 effect sizes. The effect sizes for FBS in milligrams per deciliter (mg/dl), insulin in picomoles per liter (pmol/l), hemoglobin A1C (HbA1c) in percentage (%), and homeostasis model assessment of insulin resistance (HOMA-IR) were 92, 46, 80, and 22, respectively. The pooled analysis indicated that acarbose intake resulted in significant decreases in FBS (p = 0.018), insulin (p < 0.001), HbA1c (p < 0.001), and HOMA-IR (p < 0.001).ConclusionThe findings of this systematic review and meta-analysis suggest that acarbose intake can potentially lead to significant improvements in glycemic parameters by decreasing the levels of FBS, HbA1c, and insulin. However, larger and more rigorously designed studies are still needed to further evaluate and strengthen this association.