Metformin reduces the rate of small intestinal glucose absorption in type 2 diabetes

In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon‐like peptide‐1 ( GLP ‐1) secretion. We evaluated the effects of metformin on serum 3‐O‐methylglucose (3‐ OMG ; a marker of glucose absorption) and plasma total GLP ‐1 concentrations during a standardized intraduodenal infusion of glucose and 3‐ OMG in patients with type 2 diabetes. A total of 12 patients, treated with metformin 850 mg twice daily or placebo for 7 days each in a double‐blind, randomized, crossover design (14 days’ washout between treatments), were evaluated on days 5 or 8 of each treatment (6 subjects each). On each study day, 30 minutes after ingesting 850 mg metformin or placebo, patients received an infusion of glucose (60 g + 5 g 3‐ OMG , dissolved in water to 240 mL ) via an intraduodenal catheter over the course of 120 minutes. Compared with placebo, metformin was associated with lower serum 3‐ OMG ( P < .001) and higher plasma total GLP ‐1 ( P = .003) concentrations. The increment in plasma GLP ‐1 after metformin vs placebo was related to the reduction in serum 3‐ OMG concentrations ( P = .019). Accordingly, metformin inhibits small intestinal glucose absorption, which may contribute to augmented GLP ‐1 secretion in type 2 diabetes.