Moxonidine improves insulin sensitivity in insulin-resistant hypertensives

Abstract

Objective: To study whether insulin sensitivity and insulin response are altered by moxonidine treatment in obese patients with mild essential hypertension.

Design: a prospective, double-blind, placebo-controlled, randomized, parallel group study.

Patients and methods: 77 patients with mild essential hypertension and body mass index > 27 were enrolled. A placebo run-in period of 1-3 weeks was followed by 8-9 weeks of double-blind treatment with either placebo or moxonidine. Patients receiving antihypertensive drugs underwent a 4-week wash-out period preceeding the placebo run-in. Insulin sensitivity was evaluated by hyperinsulinaemic euglycaemic clamp test. Insulin response was measured during intravenous glucose tolerance test.

Results: 72 patients completed the study. No serious adverse events were reported. The glucose infusion rate (M value), and insulin sensitivity index (M/I ratio) increased in the moxonidine-treated subjects by 10% (P = 0.025), and 11% (P = 0.04), respectively, whereas the values in the placebo group remained unchanged. In the predefined insulin-resistant subgroup with M/I ratio < 3.6 at baseline, glucose infusion rate and insulin sensitivity index increased by 21% whereas values in the placebo group remained unchanged. A between-group comparison showed a statistical significant difference in the M value (P = 0.026) and a borderline statistical difference in the M/I ratio (P = 0.056) in favour of moxonidine. No statistically significant effects were seen in the subgroup with a M/I ratio > or = or 3.6 at baseline. The insulin secretion in response to glucose stimulation was unaffected in insulin-resistant as well as in insulin-sensitive hypertensive patients.

Conclusion: Moxonidine treatment improved insulin sensitivity in insulin-resistant, obese patients with mild hypertension, but not in insulin-sensitive obese subjects with mild hypertension, when compared to placebo. Insulin response to glucose stimulation was unaffected. The drug was well tolerated.