The beneficial effect of metformin on β-cell function in non-obese Chinese subjects with newly diagnosed type 2 diabetes

Abstract

Aim: Studies with metformin suggest a favourable change in β-cell function over sulphonylureas in the early course of obese type 2 diabetes mellitus (T2DM), but it remains unclear whether a similar effect is observed in non-obese individuals. Here we investigated the effects of metformin or glipizide gastrointestinal therapeutics system extended-release formulation (GITS) on β-cell function in non-obese patients with newly diagnosed T2DM.

Methods: A total of 160 newly diagnosed patients with fasting glucose 7.0-13.0 mmol/L and body mass index <30 kg/m(2) from five centres in China were randomized to metformin or glipizide GITS for 24 weeks. Early insulin secretion [the ratio of area under the curve (AUC) of insulin to glucose during 0-30 min (InsAUC30 /GluAUC30 )] and insulin sensitivity [Matsuda index (ISIM )] were assessed during the standard meal tolerance test before and after therapy. Plasma glucagon-like peptide-1(GLP-1) and glucagon levels were also measured.

Results: Metformin improved InsAUC30 /GluAUC30 significantly (from 8.1 ± 0.6 pmol/mmol to 10.7 ± 0.7 pmol/mmol, p < 0.05), comparable to results with glipizide GITS. In the metformin-treated lean (body mass index < 25 kg/m(2) ) subgroup, the increase in ISIM was not significant, but the improvement in InsAUC30 /GluAUC30 was of great magnitude. Increased GLP-1 responses during meal tolerance test and decreased fasting glucagon level were observed after metformin treatment. Correlation analysis showed that the improvement of InsAUC30 /GluAUC30 was associated with the changes in HbA1c (r = -0.374, p = 0.000), ISIM (r = 0.356, p = 0.001), and ΔGLP-10-30 (r = 0.225, p = 0.02).

Conclusions: Metformin improved β-cell function in non-obese subjects with newly diagnosed T2DM, which was partly independent of the change in insulin sensitivity in these subjects. This study provides evidence-based data to support metformin use in non-obese patients with T2DM as the first-line agent, which can improve both insulin sensitivity and β-cell function.

Keywords: beta cell function; glucagon; glucagon-like peptide-1; metformin; non-obese; type 2 diabetes mellitus.