Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide1 and ghrelin in obese patients with Type 2 diabetes mellitus

Abstract

Aims Studies investigating the acute effects of metformin have demonstrated actions on the incretin system and appetite regulatory hormones. There are limited data to support that these effects are sustained in the long term. We therefore studied the effects of chronic treatment with metformin on endogenous glucagon-like peptide1, dipeptidyl peptidase-4 activity and active ghrelin (an orexigenic hormone) in obese patients with Type2 diabetes mellitus. Methods Eight subjects [six male, age 58.7±2.6years, BMI 41.1±2.9kg/m 2, HbA 1c 69±6mmol/mol (8.5±0.5%), mean±sem] with drug-naïve Type2 diabetes were studied for 6h following a standard mixed meal, before and after at least 3months of metformin monotherapy (mean dose 1.75g daily). Results The area under the curve (AUC 0-6h) for active glucagon-like peptide1 was significantly higher on metformin (pre-metformin 1750.8±640pmoll -1min -1 vs. post-metformin 2718.8±1182.3pmoll -1min -1; P=0.01). The areas under the curves for dipeptidyl peptidase-4 activity and ghrelin were not significantly different pre- and post-treatment with metformin. Conclusion Three months or more of metformin monotherapy in obese patients with Type2 diabetes was associated with increased postprandial active glucagon-like peptide1 levels. The effects of metformin on the enteroinsular axis may represent yet another important mechanism underlying its glucose-lowering effects. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.