Influence of telmisartan on insulin response after glucose loading in obese patients with hypertension: ARB trial of hypertension in obese patients with hyperinsulinemia assessed by oral glucose tolerance test (ATHLETE).
ABSTRACT The number of patients with both hypertension and obesity has been increasing in Japan. Many of these patients may also have insulin resistance. Telmisartan, an angiotensin II receptor blocker (ARB), selectively activates peroxisome proliferatoractivated receptor (PPAR)-gamma, and this effect is considered to markedly improve insulin resistance in obese patients with hypertension. We compared the antihypertensive and insulin resistance-improving effects of telmisartan with those of candesartan and valsartan in this patient population.
Twenty-eight elderly patients with an average body mass index (BMI) of 27.1 kg/m(2) were enrolled in this 6-month study. Patients were randomly selected to either switch from candesartan or valsartan to telmisartan or to continue with their current ARB. A 75 g oral glucose tolerance test (OGTT) was performed before and after switching, and the effect of telmisartan on the insulin response to glucose loading was investigated.
There was no significant difference in blood pressure between the two groups after drug administration, but glucose tolerance significantly improved in the telmisartan group. The hyperinsulin response to glucose loading also significantly improved in those taking telmisartan, as well as homeostasis model assessment of insulin resistance (HOMA-IR). These changes were not observed in the control group.
In patients with hypertension and obesity showing insulin resistance, treatment with telmisartan significantly improved the hyperinsulin response to glucose loading. Telmisartan may therefore be beneficial in these patients.
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ABSTRACT: An association exists between hyperaldosteronism, hypertension and impaired insulin action. Eplerenone is a selective mineralocorticoid receptor antagonist; however, little is known about its effects on insulin action. The aim of this study was to determine the effect of eplerenone on insulin action in hypertensive adults, using the hyperinsulinaemic euglycaemic clamp. A randomised, controlled, double-blind, crossover design was employed. After a 6-week washout period, hypertensive, non-diabetic patients were treated with either eplerenone 25 mg twice daily or doxazosin 2 mg twice daily for 12 weeks. After each treatment period, insulin action was assessed by a hyperinsulinaemic euglycaemic clamp, with isotope dilution methodology. After washout, treatment groups were crossed over. Fifteen patients completed the study. There were no differences in fasting glucose, or fasting insulin between treatment with eplerenone or doxazosin. The measure of overall insulin sensitivity, exogenous glucose infusion rates during the last 30 min of the clamp, was similar with both treatments; 23.4 (3.9) μmol kg(-1) min(-1) after eplerenone and 23.3 (3.6) μmol kg(-1) min(-1) after doxazosin (P=0.83). Isotopically determined fasting endogenous glucose production rates were similar after both treatments (eplerenone 9.4 (0.6) μmol kg(-1) min(-1) vs doxazosin 10.6 (0.7) μmol kg(-1) min(-1)). There was a trend for lower endogenous glucose production rates during hyperinsulinaemia following eplerenone compared with doxazosin (2.0 (0.8) μmol kg(-1) min(-1) vs 4.1 (0.9) μmol kg(-1) min(-1)). There was no difference in insulin stimulated peripheral glucose utilisation rates after treatment with eplerenone or doxazosin (25.4 (3.6) μmol kg(-1) min(-1) vs 27.0 (3.9) μmol kg(-1) min(-1)). This study gives reassuring evidence of the neutral effect of eplerenone on insulin action in hypertensive, non-diabetic patients.Journal of Human Hypertension advance online publication, 17 April 2014; doi:10.1038/jhh.2014.19.Journal of human hypertension 04/2014; DOI:10.1038/jhh.2014.19 · 2.69 Impact Factor
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ABSTRACT: Telmisartan is expected to ameliorate not only hypertension, but also metabolic syndrome as a metabosartan. We examined the effects of telmisartan on metabolic syndrome-related molecules such as insulin receptor (IR), peroxisome proliferator-activated receptor gamma (PPAR-γ), and angiotensin 2 type 1 receptor (AT1R) in stroke-resistant spontaneously hypertensive rat (SHR-SR) after transient middle cerebral artery occlusion (tMCAO), by administering telmisartan at either 0 (vehicle), .3 mg/kg/day (low dose), or 3 mg/kg/day (high dose), postoperatively, from 3 months of age and performed immunohistologic analysis at 6, 12, and 18 months of age. Compared with the vehicle group, the 2 telmisartan groups dose dependently decreased the number of IR- and AT1R-positive neurons in the cerebral cortex in the ipsilateral cerebral cortex from 6 to 18 months after tMCAO. On the other hand, the number of PPAR-γ-positive neurons increased in a dose-dependent manner in the 2 telmisartan groups from 6 to 18 months. The present study suggests that telmisartan dose-dependently ameliorated metabolic syndrome-related changes in the poststroke brain of SHR-SR with a direct protective effect (low dose) and an additive benefit, an antihypertensive effect at a high dose, for long-term protection after tMCAO.Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 10/2014; 23(10). DOI:10.1016/j.jstrokecerebrovasdis.2014.06.012 · 1.99 Impact Factor
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ABSTRACT: To determine whether telmisartan improves insulin resistance compared with other antihypertensive drugs, we performed a meta-analysis of randomized controlled trials (RCTs) of telmisartan. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through December 2013. Eligible studies were prospective RCTs of telmisartan versus other antihypertensive drugs enrolling individuals with hypertension and reporting insulin levels and/or homeostasis model assessment-insulin resistance (HOMA-IR) as outcomes. Of 67 potentially relevant articles screened initially, 33 reports of RCTs enrolling a total of 2033 patients with hypertension were identified and included. Pooled analyses of only the 8 double-blind-design trials demonstrated statistically significant reductions in percent changes of insulin levels (mean difference, –5.19; 95% confidence interval, –8.94 to –1.43; P = .007) and HOMA-IR (–15.34; –26.39 to –4.28; P = .007) with telmisartan relative to other antihypertensive drugs. When data from all the 33 trials were pooled, telmisartan was associated with statistically significant reductions in percent changes of insulin levels (–10.92; –15.60 to –6.23; P < .00001) and HOMA-IR (–15.89; –22.01 to –9.78; P < .00001) relative to other antihypertensive drugs. In conclusion, telmisartan appears to significantly improve insulin resistance compared with other antihypertensive drugs in patients with hypertension.Journal of the American Society of Hypertension 08/2014; 8(8). DOI:10.1016/j.jash.2014.05.006 · 2.68 Impact Factor