Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertension

Background: Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. Patients and Methods: A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. Results: Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54+1.72 to 7.54+1.33 mmol/l, p<0.05), although HbA(1c) had decreased in both groups (PG: 6.7<plus/minus>3.0 to 5.9 +/-2.6%; MG: 5.3 +/-1.5 to 4.6 +/-0.9%; p<0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7<plus/minus>8.0 to 99.2 +/-9.3 mmHg, p<0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0<plus/minus>62.4 to 38.0 +/- 23.0 pmol/l, p<0.05) and the insulin resistance index (3.5<plus/minus>2.7 to 1.8 +/-1.0, p<0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8<plus/minus>7.9 to 21.4 +/- 14.6 mug/l; MG: 18.5 +/- 10.3 to 18.4 +/-8.9 mug/l). Dopamine levels increased significantly only in metformin-treated subjects. Conclusions: Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels.