Effects of Metformin on Postprandial Blood Pressure, Heart Rate, Gastric Emptying, GLP-1, and Prevalence of Postprandial Hypotension in Type 2 Diabetes: A Double-Blind Placebo-Controlled Crossover Study

Individuals with type 2 diabetes are at high risk of postprandial decrease in blood pressure (BP; i.e., a reduction in systolic BP of ≥20 mmHg, termed postprandial hypotension [PPH]), which increases the risk of falls and mortality. This study evaluated the effects of oral metformin on postprandial BP, heart rate (HR), glucagon-like peptide 1 (GLP-1), and gastric emptying (GE) in individuals with type 2 diabetes. We studied 16 patients (five women) before and after ingestion of a 75-g radiolabeled glucose drink, after both acute (30 min) and subacute (twice per day for 7 days) administration of metformin (850 mg) or placebo, according to a double-blind randomized crossover design. To quantify PPH events, 24-h ambulatory BP measurement after standardized meals (breakfast, lunch, and dinner) was used. The primary outcome was postprandial decrease in systolic BP. We found that acute administration of metformin did not affect BP, HR, plasma insulin, or GLP-1 levels but slowed GE (P < 0.001) and reduced glycemic response to oral glucose (P < 0.001). Subacute metformin increased HR (P = 0.029), slowed GE (P < 0.001), augmented plasma GLP-1 (P < 0.001) and reduced plasma glucose (P < 0.001) in response to oral glucose, without affecting plasma insulin. Moreover, subacute metformin reduced postprandial falls in systolic BP (P = 0.0002) and PPH events (P = 0.035) during ambulatory BP measurement. Preprandial BP was unaffected by metformin. To conclude, in type 2 diabetes, oral metformin attenuates the hypotensive response to meals, in association with stimulation of GLP-1 and slowing of GE, to reduce PPH.