Lower Diabetes Incidence in Patients Treated With ACEIs and ARBs

Gregory A. Nichols, PhD


May 25, 2011

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers and Diabetes: A Meta-Analysis of Placebo-Controlled Clinical Trials

Tocci G, Paneni F, Palano F, et al
Am J Hypertens. 2011;24:582-590

Study Summary

This meta-analysis used 11 randomized, placebo-controlled clinical trials, with a total of 84,363 patients, to study whether the administration of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) reduced the incidence of new-onset diabetes. For each trial, data were derived from the published tables or texts that included total number of patients; number of patients with and without diabetes mellitus at baseline; type and dosage of study drugs (ACEIs or ARBs); mean duration of follow-up; number of patients who developed diabetes (among those without diabetes at baseline); and number of patients who experienced fatal events due to cardiovascular (CV) or non-CV causes. The primary endpoint of the present analysis was diabetes incidence in both the active (ACEIs or ARBs) and comparator (placebo) groups. Secondary endpoints of the study were diabetes incidence in a variety of subgroups (high CV risk with or without hypertension, coronary artery disease, stroke, heart failure, and specific antihypertensive drugs).

Of the 11 trials, 1 was designed to directly test the effects of ACEIs and 1 to directly test the effects of ARBs on diabetes incidence. Five were designed to compare ACEIs against placebo, and 6 compared ARBs against placebo. In the ACEI trials, 15,142 nondiabetic patients were randomly assigned to ACEIs and 15,130 to placebo. In the ARB trials, 18,756 patients were randomly assigned to ARBs and 18,800 to placebo. Over an average follow-up of 4.0 +/- 1.0 years, there were 1284 (8.5%) incident cases of diabetes in active-treated and 1411 (9.3%) cases in placebo-treated patients in the ACE inhibitor trials, and there were 2330 (12.4%) cases in active-treated and 2669 (14.2%) cases in placebo-treated patients in the ARB trials. Overall, active therapy reduced diabetes incidence compared with placebo (odds ratio [OR], 0.8; 95% confidence interval [CI], 0.8-0.9; P < .01). ARBs significantly reduced diabetes incidence (OR, 0.8; CI, 0.8-0.9; P < .01). Incidence was also lower for ACEIs (OR, 0.8; CI, 0.7-1.0) but was only marginally significant (P = .07).


Ten years ago, the Heart Outcomes Prevention Evaluation (HOPE) study reported that ramipril reduced diabetes incidence by 34% compared with placebo.[1] Since then, other trials have suggested that renin-angiotensin system blockade may prevent diabetes,[2] but none of those studies had evaluated diabetes as a primary outcome. Recently, however, the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial included a ramipril arm, and Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) included a valsartan arm in studies of diabetes prevention.[3,4] DREAM did not show a diabetes-reduction benefit; however, regression from impaired glucose tolerance to normoglycemia (a secondary outcome) was more common with ramipril (OR, 1.16; CI, 1.07-1.27). NAVIGATOR reported a reduction in diabetes incidence of 14% (OR, 0.86; CI, 0.80-0.92) with valsartan. The findings of the current meta-analysis are consistent with those 2 trials; researchers found lower but nonstatistically significant diabetes incidence with ACEIs, and significantly lower incidence with ARBs. However, if pharmacotherapy for diabetes prevention is the goal, metformin or pioglitazone are clearly better options.[5,6] However, when treating hypertension in patients at risk of developing diabetes, these results along with recent clinical trials suggest that all else being equal, ARBs may provide some additional antihyperglycemic benefit.



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