Objectives: To study the effect of metformin on blood pressure and metabolism in nondiabetic hypertensives.
Design: A six-week single-blind placebo wash-out, followed by a double-blind placebo-controlled parallel group design with skew randomization (2:2:1) to metformin 850 mg b.i.d. (n = 10), metformin 500 mg b.i.d. (n = 10), or placebo b.i.d. (n = 5) for 12 weeks. Office blood pressure (oBP), ambulatory blood pressure (aBP), lipoproteins, and oral glucose tolerance (OGTT) were measured/performed before and during treatment.
Subjects: Sixteen male and nine female nondiabetic (OGTT) patients (median age 57 (39-74) years) with verified hypertension (White-coat excluded) for 4 (0-20) years.
Results: The possible effect of metformin treatment and dosage was tested with a two-factor analysis of variance. Treatment induced a significant decline in diastolic oBP, P < 0.05. This decline was, however, not significantly different comparing metformin and placebo. Systolic oBP, diastolic aBP, and systolic aBP showed no significant change by treatment. The decline in diastolic oBP was 5 mmHg in the pooled group of metformin-treated patients, P < 0.005. Different gender and the presence of obesity had no impact on the decline in diastolic oBP within this group. Changes in fasting C-peptide and fasting insulin during treatment were unrelated to blood pressure changes. High fasting insulin (> 60 pmol L[-1]) or high fasting C-peptide (> 1000 pmol L[-1]) at baseline did not favour an effect of metformin on diastolic oBP. Glucose metabolism and lipoproteins were unchanged in all groups.
Conclusions: Although metformin treatment induced a decline in diastolic office blood pressure in nondiabetic hypertensives, the decline was not different from that during placebo treatment. Metformin had no significant effect on ambulatory blood pressure. Thus, metformin has, if any, only a minor clinically insignificant effect on blood pressure in nondiabetic hypertensives. The study does not support the hypothesis that circulating insulin is a major regulator of blood pressure in hypertension.
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