Effect of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Blockers on the Rate of New‐Onset Diabetes Mellitus: A Review and Pooled Analysis

The rising prevalence and health burden of diabetes mellitus require that new approaches for prevention among high-risk populations be evaluated. Emerging evidence from the prospective evaluations of secondary and tertiary outcomes and from retrospective evaluations in randomized controlled trials suggests that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARBs) may reduce the occurrence of new-onset diabetes. Therefore, we each independently searched MEDLINE for randomized controlled trials from January 1966-October 2005 that used an ACE inhibitor or ARB as a primary intervention versus a control group not receiving an ACE inhibitor or ARB and that reported the occurrence of diabetes. Thirteen trials were identified. In each of the 13 studies, the frequency of diabetes in the ACE inhibitor or ARB groups was lower than that in the control groups. In addition, it was consistent in that no study significantly excluded any benefit from ACE inhibitors or ARBs on the rate of new-onset diabetes. The combined occurrence of new-onset diabetes in all 13 studies was 2249 cases among 31,283 patients (7.2%) in the ACE inhibitor or ARB group versus 3230 cases among 35,988 patients (9.0%) in the control group. The combined relative risk of diabetes was 0.80, with a 95% confidence interval of 0.76-0.84, based on a two-sided alpha of 0.05, in favor of ACE inhibitors and ARBs. This observation needs to be confirmed by randomized controlled trials with the frequency of diabetes as the primary prospective end point.