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The Impact of ACE Inhibitors or Angiotensin II Type 1 Receptor Blockers on the Development of New-Onset Type 2 Diabetes

¹ School of Pharmacy, University of Connecticut, Storrs, Connecticut
² Department of Pharmacy, Hartford Hospital, Hartford Connecticut
³ Department of Medicine, University of Connecticut School of Medicine, Farmington, Connecticut
⁴ Department of Medicine, Hartford Hospital, Hartford, Connecticut

Address correspondence and reprint requests to Craig I. Coleman, PharmD, Hartford Hospital, 80 Seymour St., CB 309, Hartford, CT 06102-5037. E-mail: ccolema{at}harthosp.org

ABSTRACT

OBJECTIVE—Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity. Patients who utilize either an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) may experience a decreased incidence of new-onset type 2 diabetes.

RESEARCH DESIGN AND METHODS—Three reviewers conducted a systematic literature search of Medline, EMBASE, CINAHL, and the Cochrane Library (1966 to present) to extract a consensus of trial data involving an ACEI or ARB with an end point of new-onset type 2 diabetes. Studies were included if they were randomized controlled trials verses placebo/routine therapy. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted.

RESULTS—Eleven trials were identified, including 66,608 patients. An ACEI or ARB prevented new-onset type 2 diabetes (odds ratio 0.78 [95% CI 0.73–0.83]). The influence of either an ACEI (six trials) or an ARB (five trials) alone on new-onset type 2 diabetes was similar (0.79 [0.71–0.89] and 0.76 [0.70–0.82], respectively). Regardless of indication for use, hypertension (seven trials), coronary artery disease (two trials), or heart failure (two trials), reductions in new-onset type 2 diabetes were maintained (0.79 [0.72–0.85], 0.76 [0.60–0.95], and 0.70 [0.50–0.96], respectively). No statistical heterogeneity was observed for any evaluation (P > 0.1 for all comparisons). ACEIs and ARBs did not reduce the odds of mortality, cardiovascular, or cerebrovascular events versus control therapy among all of these studies combined or the hypertension trials. ACEIs and ARBs did reduce the odds of these outcomes among the coronary artery disease studies versus control therapy.

CONCLUSIONS—ACEIs or ARBs may decrease patients’ odds of developing new-onset type 2 diabetes but does not reduce the odds of mortality, cardiovascular, or cerebrovascular outcomes over the study follow-up periods among patients with hypertension.

Abbreviations: ACEI, ACE inhibitor • ARB, angiotensin receptor blocker

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