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ACE Inhibition for Preventing Diabetes: Still Just a DREAM

Ramipril fell short in a large, randomized, placebo-controlled trial.

Can a drug that inhibits the renin-angiotensin system reduce the risk for developing diabetes? Researchers addressed this question in the ACE-inhibitor arm of the partly industry-supported Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial. Subjects were 5269 patients (minimum age, 30; mean age, 55; 59% women) without histories of cardiovascular disease or diabetes but with impaired fasting glucose levels (110–125 mg/dL), impaired glucose tolerance (140–200 mg/dL 2 hours after loading), or both.

The DREAM trial was placebo-controlled with a 2x2 factorial design; for results of the rosiglitazone arm, see Journal Watch Cardiology Oct 18 2006. Subjects first entered a 17-day, single-blind, double-placebo, run-in period to check adherence. Then, in the ACE-inhibitor arm, they were randomized to receive placebo or ramipril (5 mg daily for 2 months, 10 mg for the next 10 months, then 15 mg). Median follow-up was 3 years.

Mean systolic blood pressure decreased from 136 mm Hg at baseline in both groups to on-treatment means of 128 mm Hg with ramipril and 132 mm Hg with placebo. Neither group’s mean creatinine level changed significantly. During follow-up, incidence of the primary composite endpoint — new diabetes or death — was 18.1% with ramipril and 19.5% with placebo (P=0.15); new diabetes incidences were 17.1% and 18.5%, respectively. The groups also did not differ in the incidence of cardiovascular events or hospitalization, but significantly more ramipril than placebo recipients regressed to normoglycemia (43% vs. 38%).

Comment: This study failed to support the hypothesis that the ACE inhibitor ramipril can reduce the risk for new diabetes in patients at high risk for that condition. The authors speculate that a longer or larger study might show an effect. For now, the emphasis should remain on lifestyle changes to reduce a patient’s risk for developing diabetes.

— Harlan M. Krumholz, MD, SM

Published in Journal Watch Cardiology October 25, 2006

Citation(s):

The DREAM Trial Investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006 Oct 12; 355:1551-62.

• Original article (Subscription may be required)
• Medline abstract (Free)

Ingelfinger JR and Solomon CG. Angiotensin-converting–enzyme inhibitors for impaired glucose tolerance — Is there still hope? N Engl J Med 2006 Oct 12; 355:1608-10.

• Original article (Subscription may be required)
• Medline abstract (Free)