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.