Improved insulin sensitivity by the angiotensin receptor antagonist irbesartan in patients with systolic heart failure: A randomized double-blinded placebo-controlled study

BackgroundImpaired insulin sensitivity is common in patients with chronic systolic heart failure (CHF) and contributes to symptomatic status and impaired prognosis. A specific metabolic effect to improve insulin sensitivity in diabetic patients has been reported for some but not all angiotensin II-receptor antagonists. We aimed to test the ancillary metabolic effect of irbesartan on insulin sensitivity in patients with CHF.Methods and participantsIn this placebo-controlled double-blinded study 36 non-diabetic patients with stable ischemic CHF (age 63 ± 9 years, peak VO2 16.6 ± 4.8 ml/kg/min, LVEF 32 ± 9%) were randomized to irbesartan 300 mg/d vs placebo on top of standard CHF therapy. Body composition (dual energy X-ray absorptiometry), clinical status, peripheral vasodilator capacity (plethysmography) and neuroendocrine and metabolic profiles were assessed. Primary endpoint was the change of whole body insulin sensitivity after 4 months of treatment assessed by intravenous glucose tolerance testing and minimal modeling.ResultsInsulin sensitivity improved by 26% (p < 0.001) in the irbesartan group, but not in the placebo group (treatment effect: 1.044 min− 1·μU·ml− 1·104; 95%CI 0.45 to 1.64, p = 0.0026). Treatment effects on systolic and diastolic blood pressure were − 11 (95%CI − 21 to − 1) mm Hg and − 8 (95%CI − 15 to − 3) mm Hg, respectively. Peripheral vasodilator capacity improved by 14% (p = 0.016). Change in insulin sensitivity correlated with increased vasodilator capacity (R = 0.47, p = 0.021). Body composition and clinical status were not different after 4 months of therapy. Also adiponectin, resistin, cytokine profile, and asymmetric dimethylarginine (ADMA) were not changed after this short-term intervention.ConclusionTherapy with irbesartan improved insulin sensitivity in patients with chronic heart failure. Improved peripheral vasodilator capacity may contribute to the metabolic effect. (Clinical trials identifier: NCT00347087).