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

Abstract

Background: Impaired 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 participants: In this placebo-controlled double-blinded study 36 non-diabetic patients with stable ischemic CHF (age 63 ± 9 years, peak VO(2) 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.

Results: Insulin 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)·10(4); 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)mmHg and -8 (95%CI -15 to -3)mmHg, 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.

Conclusion: Therapy 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).