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« on: April 01, 2007, 08:55:52 am » |
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Came across these 2 studies:
Haenni A, Lithell H. Moxonidine improves insulin sensitivity in insulin-resistant hypertensives. J Hypertens Suppl. 1999 Aug;17(3):S29-35.
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.
Chazova I, Almazov VA, Shlyakhto E. Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin. Diabetes Obes Metab. 2006 Jul;8(4):456-65.
AIM: To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. METHODS: A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients > or =40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. RESULTS: With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1-35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. CONCLUSIONS: Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease.
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