Moxonidine improves insulin sensitivity in insulin-resistant hypertensives.
OBJECTIVE
To study whether insulin sensitivity and insulin response are altered by moxonidine treatment in obese patients with mild essential hypertension.


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


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.


CONCLUSIONS
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.
Haenni
A
A
Department of Public Health and Caring Sciences/Geriatrics, Uppsala, Sweden. arvo.hanni@geriatrik.uu.se
Lithell
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D007093:Imidazoles; D007328:Insulin; D008055:Lipids; C043482:moxonidine