Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure

Background - Diabetes is a risk factor for heart failure, and both conditions are increasing. Identifying treatments that prevent both conditions will be clinically important. We previously reported that candesartan ( an angiotensin receptor blocker) reduces cardiovascular mortality and heart failure hospitalizations in heart failure patients ( CHARM: Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity Program). Methods and Results - We assessed the impact of candesartan versus placebo on the development of diabetes, a predefined secondary outcome in a randomized, controlled, double-blind study involving 5436 of the 7601 patients with heart failure, irrespective of ejection fraction, who did not have a diagnosis of diabetes at entry into the trial. Patients received candesartan ( target of 32 mg once daily) or matching placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo group ( hazard ratio [HR], 0.78 with a 95% confidence interval [CI] of 0.64 to 0.96; P = 0.020). The composite end point of death or diabetes occurred in 692 (25.2%) and 779 ( 28.6%), respectively, in the candesartan and placebo groups ( HR, 0.86; 95% CI, 0.78 to 0.95; P = 0.004). The results were not statistically heterogeneous in the various subgroups examined, although the apparent magnitude of benefit appeared to be smaller among those treated concomitantly with angiotensin-converting enzyme inhibitors at trial entry ( HR, 0.88; 95% CI, 0.65 to 1.20) compared with those not receiving these drugs ( HR, 0.71; 95% CI, 0.53 to 0.93; P for heterogeneity, 0.28). Conclusions - The angiotensin receptor blocker candesartan appears to prevent diabetes in heart failure patients, suggesting that the renin-angiotensin axis is implicated in glucose regulation.