1.
Treatment of hypertension in metabolic syndrome subjects with amlodipine and olmesartan-effects on oxidized non-esterified free fatty acids and cytokine production.
Rosenson, RS
Cardiovascular drugs and therapy. 2009;(4):289-94
Abstract
PURPOSE Angiotensin II increases activation of oxidative signaling and vascular inflammatory gene expression, and interruption of the renin-angiotensin system has been considered more vasculoprotective than use of calcium channel antagonists and other anti-hypertensive therapies. Despite these putative mechanisms, amlodipine is equally efficacious as other therapies in reducing cardiovascular events. METHODS Double-blind, controlled trial, designed to investigate the effects of 2-months treatment with amlodipine and olmesartan on oxidized non-esterified fatty acids (ox-NEFA), and lipopolysaccharide-stimulated cytokine production in whole blood among 23 hypertensive subjects with the metabolic syndrome. RESULTS Treatment with olmesartan was no different than amlodipine in changing concentrations of total oxidized fatty acids (p = 0.37), total ox-NEFA (p = 0.43) and 9, 10, 11, 12, 13, 14, 15 and 16 ox-NEFA concentrations. In contrast, 8 ox-NEFA increased (median [interquartile ranges] by 45.2% [5.3 to 50.0] in olmesartan-treated subjects) compared with a decrease of 18.4% (-45.1-13.9) in amlodipine-treated subjects (p = 0.03). Lipopolysaccharide-stimulated cytokine production and levels of soluble cellular adhesion molecules did not change with either treatment. CONCLUSION Despite experimental data that demonstrates that angiotensin receptor antagonists reduce cellular oxidant stress and inflammation, olmesartan was not different than amlodipine in changing ox-NEFA and inflammatory markers in hypertensive subjects with the metabolic syndrome.
2.
Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin.
Chazova, I, Almazov, VA, Shlyakhto, E
Diabetes, obesity & metabolism. 2006;(4):456-65
Abstract
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.