Mechanism of increase in plasma intact GLP-1 by metformin in type 2 diabetes: Stimulation of GLP-1 secretion or reduction in plasma DPP-4 activity?

• Acute dosing of metformin has no effect on plasma DPP-4 activity.
• Prolonged exposure to metformin suppresses plasma DPP-4 activity.
• Metformin increases GLP-1 secretion during an intraduodenal glucose infusion.
• Metformin may enhance L-cell secretion directly.
• Metformin appears to suppress plasma DPP-4 activity indirectly.

Metformin was reported to increase plasma intact glucagon-like peptide-1 (GLP-1) concentrations in type 2 diabetes. This is, at least partly, attributable to stimulation of GLP-1 secretion. A reduction in soluble dipeptidyl peptidase-4 activity may also make a modest contribution.