Effects of metformin on postprandial blood pressure, heart rate, gastric emptying, GLP-1 and the 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 falls in blood pressure (BP) (i.e., a reduction in systolic BP of ≥20mmHg, 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 subjects (5 female) before and after ingestion of a 75g radiolabeled glucose drink, after both acute (30 min) and subacute (b.i.d for 7 days) administration of metformin (850mg) or placebo, in a double-blind, randomized, crossover design. 24-hour ambulatory BP measurement following standardized meals (breakfast, lunch and dinner) was used to quantify PPH events. The primary outcome was the postprandial fall 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 the glycemic response to oral glucose (P<0.001). Sub-acute metformin reduced PPH events by 32% (P=0.035), in association with an increase in HR (P=0.029), slowing of GE (P<0.001), augmentation of plasma GLP-1 (P<0.001), and a reduction in plasma glucose (P<0.001) without affecting plasma insulin. Pre-prandial BP was unaffected by metformin. To conclude, in type 2 diabetes oral metformin attenuates the hypotensive response to meals, associated with stimulation of GLP-1 and slowing of GE to reduce PPH.