Alpha-glucosidase inhibitors and hepatotoxicity in type 2 diabetes: a systematic review and meta-analysis

Abstract

Alpha-glucosidase inhibitors (AGIs) was reported to be associated with several rare adverse hepatic events, but with inconsistent results. We aimed to investigate the risk of hepatotoxicity associated with the use of AGIs in patients with type 2 diabetes mellitus (T2DM), and performed a systematic review and meta-analysis. Fourteen studies (n = 2881) were eligible, all of which were RCTs. Meta-analysis of data regarding elevation of more than 3-fold the upper limit of normal (ULN) of AST and ALT showed statistically significant differences between AGIs treatment versus control (OR 6.86, 95% CI 2.50 to 18.80; OR 6.48, 95% CI 2.40 to 17.49). Subgroup analyses of elevation of more than 1.8-fold ULN of AST and ALT by dose of AGIs showed differential effects on AST and ALT (AST: OR 0.38 vs 7.31, interaction P = 0.003; ALT: OR 0.32 vs 4.55, interaction p = 0.02). Meta-analysis showed that AGIs might increase the risk of hepatotoxicity, and higher dose appeared to be associated with higher risk of hepatotoxicity. However, the evidence is limited with surrogate measures (i.e. ALT and AST), and no clinically important adverse events were observed.Alpha-glucosidase inhibitors (AGIs) are commonly used oral hypoglycemic drugs, especially in the patient population from East Asia 1-3 . The guideline of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommended the use of AGIs as a potentially first-line agent or in combination with other antihyperglycemic drugs 4 . AGIs has proven similarly efficacious as other commonly used antidiabetes agents [5][6][7] . A recent large trial 1 showed that acarbose is similar to metformin in terms of efficacy, and supports a viable choice for initial therapy in patients with newly diagnosed type 2 diabetes. Additionally, AGIs do not increase body weight, rarely cause hypoglycemia; and have minimal drug-drug interactions 1,7,8 . Meanwhile, AGIs was reported to be associated with several rare adverse hepatic events 9-11 and increase liver enzyme levels [12][13][14][15][16][17][18] . The causal relationship, however, has not been established 9 , and the magnitude of effect on the increase of liver enzyme levels remains unclear. Because these issues are often treated as adverse effects issues, and the hepatic adverse events, if any, are usually rare, individual trials are not adequate to address these important clinical questions. A meta-analysis -in which multiple studies are pooled -may offer opportunity to detect a small but clinically important difference.Thus, we carried out a systematic review of randomized controlled trials and observational studies to assess the association between hepatotoxicity and AGIs. We hypothesized that hepatotoxicity would be more frequently manifested in AGIs as opposed to no use. Figure 1 showed the study selection process. We acquired 5,318 reports. After title and abstract screening, 178 were potentially eligible (including 159 potentially relevant RCTs and 19 potentially relevant observational studies [1...

High‐theabrownins instant dark tea product by Aspergillus niger via submerged fermentation: α‐glucosidase and pancreatic lipase inhibition and antioxidant activity

“…The high‐TB instant dark tea from the present study had an inhibition rate of 81.8%, which was the highest α ‐glucosidase inhibitory activity among all of the tested instant dark tea samples. α ‐Glucosidase inhibitors could hinder the rapid absorption of carbohydrates by the body, comprising a postprandial hyperglycemia treatment . He et al reported that different molecular levels of TB (≤3.5, 3.5–25, 25–50, 50–100 and ≥ 100 kDa) had an effect on hypoglycemia, particularly 25–50 kDa TB, which was 1.9 times as active as acarbose.…”

“…-Glucosidase inhibitors could hinder the rapid absorption of carbohydrates by the body, comprising a postprandial hyperglycemia treatment. 30,31 He et al 32 reported that different molecular levels of TB (≤3.5, 3.5-25, 25-50, 50-100 and ≥ 100 kDa) had an effect on hypoglycemia, particularly 25-50 kDa TB, which was 1.9 times as active as acarbose. In addition, tea polysaccharides, 33 tea polyphenols 34 and theaflavins 35 had an inhibitory effect on -glucosidase activity.…”

HPLC‐QTOF‐MS/MS profiling, antioxidant, andα‐glucosidase inhibitory activities ofPyracantha fortuneanafruit extracts

“…Currently, numerous synthetic AGIs, such as acarbose, miglitol, and voglibose, are exactly efficient in attenuating the rise of blood glucose levels. However, side effects including liver toxicity and adverse gastrointestinal symptoms have seriously limited their application in clinical treatment (Zhang, Chen et al, ). Thus, AGIs, which have no adverse or unwanted secondary effects, are urgently needed.…”

Antioxidant, metabolic enzymes inhibitory ability of Torreya grandis kernels, and phytochemical profiling identified by HPLC‐QTOF‐MS/MS

“…Efficient α‐glucosidase inhibitors (AGIs) is currently taken as a promising proposal to suppress blood glucose level, which then prevents diabetes and diabetic complications (Ali, Houghton, & Soumyanath, ; Tiwari, Kumbhare, Agawane, Ali, & Kumar, ). However, acarbose, a synthetic AGIs, exhibits toxic side effects such as angina abdominis, bloating, diarrhea, and even hepatotoxicity (Zhang, Chen, et al, ). At present, many studies have proved that plant extracts possess the potential to be a better source of AGIs, which takes the advantages of natural, high‐efficiency, inexpensive, and low toxicity.…”