Effect of Inhibition of the Renin-Angiotensin System on Development of Type 2 Diabetes Mellitus (Meta-Analysis of Randomized Trials)

The increasing prevalence and costs of type 2 diabetes mellitus (DM) make strategies to prevent its development vitally important. This analysis was conducted to determine if angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevent the development of DM. Medline and the Cochrane Central Register of Controlled Trials (1966 to May 2006) were queried for prospective, randomized, placebo-controlled or active-controlled trials of ACE inhibitor or ARB therapy in adults that reported rates of new-onset diabetes during follow-up. Meta-analyses of summary statistics from individual trials were performed using a random-effects model. Thirteen trials with a total of 93,451 patients were identified. Renin-angiotensin system antagonists reduced the incidence of DM from 9% in nontreated patients to 7.1% in those treated, a 26% reduction in odds (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.66 to 0.81, p <0.001). The effect sizes were similar in trials that randomized only hypertensive subjects (OR 0.73, 95% CI 0.66 to 0.82, p <0.001) and trials that studied the impact of renin-angiotensin system inhibition on outcomes of patients with vascular disease or heart failure (OR 0.67, 95% CI 0.50 to 0.90, p = 0.008). ACE inhibitors and ARBs had comparable effects on the development of DM. In ACE inhibitor trials, the odds of developing DM were reduced by 28% (OR 0.72, 95% CI 0.63 to 0.84, p <0.001), and in the 5 ARB studies, there was a 27% reduction (OR 0.73, 95% CI 0.64 to 0.84, p <0.001) in the odds. In conclusion, evidence accumulated to date indicates that inhibition of the renin-angiotensin system may contribute to the prevention of DM.