Differential effects of imeglimin and metformin on insulin and incretin secretion-An exploratory randomized controlled trial

伊格列明和二甲双胍对胰岛素和肠促胰岛素分泌的不同影响——一项探索性随机对照试验

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作者:Ryota Usui, Yoshiyuki Hamamoto, Masahiro Imura, Yasuhiro Omori, Yuji Yamazaki, Hitoshi Kuwata, Hisato Tatsuoka, Kazuhiro Shimomura, Kenta Murotani, Yuichiro Yamada, Yutaka Seino

Aims

Imeglimin is a new oral anti-diabetic drug with a similar structure to that of metformin; however, unlike metformin, clinical trials indicate that imeglimin elicits its glucose-lowering effect mainly by enhancement of insulin secretion. The comparative effects of the two drugs on incretin secretion remains to be elucidated. Materials and

Conclusions

Unlike metformin, imeglimin enhances GIP secretion as well as GLP-1 secretion, in addition to its direct insulinotropic mechanism of glucose control, emphasizing its potential as a therapeutic option in the treatment of patients with diabetes.

Methods

A single-center, open-label, randomized controlled trial was conducted in patients with type 2 diabetes who were drug-naïve or were on a single oral hypoglycaemic agent (OHA). For patients taking a single OHA, an 8-week washout period was employed before randomization. Participants were randomized to the imeglimin group (IME, 2000 mg/day) or the metformin group (MET, 1000 mg/day), and OGTT was performed before treatment and after 12 and 24 weeks of treatment.

Results

The reduction in HbA1c at 24 weeks was similar in IME and MET. OGTT revealed a comparable decrease in post-challenge blood glucose excursion in both groups, but insulin levels were increased only in IME. Total and active glucagon-like peptide-1 (GLP-1) levels were increased in both IME and MET; however, total and active glucose-dependent insulinotropic peptide (GIP) levels were increased only in IME. Interestingly, while an increase in insulin levels in IME was positively correlated with an increase in GLP-1 at 12 weeks, it was correlated only with an increase in GIP at 24 weeks. Conclusions: Unlike metformin, imeglimin enhances GIP secretion as well as GLP-1 secretion, in addition to its direct insulinotropic mechanism of glucose control, emphasizing its potential as a therapeutic option in the treatment of patients with diabetes.

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