Opposing Effects of β-Blockers and Angiotensin-Converting Enzyme Inhibitors on Development of New-Onset Diabetes Mellitus in Patients With Stable Coronary Artery Disease

Study Questions:

What is the risk of new-onset diabetes mellitus (NOD) with beta-blockers, and would angiotensin-converting enzyme (ACE) inhibition modify this risk?


The PEACE trial randomized 8,290 patients with stable coronary artery disease (CAD) to trandolapril or placebo. Presence of NOD was assessed at each study visit over a median follow-up of 4.8 years. The authors examined the risk of NOD associated with beta-blocker use with Cox regression models adjusting for 25 baseline covariates, and tested whether this risk was modified by randomization to the ACE inhibitor.


Of 6,910 patients without diabetes mellitus at enrollment (1,179 women and 5,731 men, mean age 64 ± 8 years), 4,147 (60%) were taking beta-blockers and 733 (8.8%) developed NOD. There was a significant interaction between beta-blocker use and randomization to ACE inhibitor with respect to NOD (p = 0.028). Participants taking beta-blockers assigned to the placebo group (n = 2,090) were at increased risk for NOD adjusting for baseline covariates (hazard ratio, 1.63; 95% confidence interval, 1.29-2.05; p < 0.001), and this risk was attenuated in those assigned to trandolapril (n = 2,057; hazard ratio, 1.11; 95% confidence interval, 0.87-1.42; p = 0.39). Beta-blocker use was associated with increased risk for NOD in patients with stable CAD, and this risk was decreased in patients treated concurrently with an ACE inhibitor.


The authors concluded that ACE inhibition may attenuate the risk for glucose abnormalities observed in patients taking beta-blockers.


This study suggests that in patients with stable CAD, use of beta-blockers was associated with an increased risk for development of NOD in traditional, propensity-adjusted, and time-dependent analyses. Furthermore, there was a significant interaction between ACE inhibitor treatment assignment and beta-blocker use with respect to NOD risk such that the risk for NOD associated with beta-blockers was attenuated in participants randomized to an ACE inhibitor. These data have clinical relevance in a high-risk population of patients taking multiple medications who are potentially at risk for development of diabetes.

Clinical Topics: Atherosclerotic Disease (CAD/PAD), Statins

Keywords: Coronary Artery Disease, Follow-Up Studies, Indoles, Diabetes Mellitus

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