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Rosiglitazone, but Not Ramipril, Prevents Progression to Diabetes in Patients at Risk

The effect of rosiglitazone is similar to that reported for lifestyle changes.

Among patients at risk for progression to diabetes, metformin and acarbose therapy each modestly reduce the likelihood of progression; dietary modifications and increased exercise are more effective but are also more difficult to maintain (Journal Watch Feb 19 2002). In a new industry-funded multinational trial, researchers explored the effectiveness of rosiglitazone, ramipril, or both in patients at risk for diabetes; ramipril was studied because angiotensin-converting–enzyme inhibitors have been associated with a lower incidence of diabetes in previous trials (done for other purposes).

Researchers randomized more than 5000 nondiabetic patients with either elevated fasting glucose levels (110–125 mg/dL) or impaired glucose tolerance (plasma glucose, 140–199 mg/dL 2 hours after a 75-gm glucose challenge) to receive daily rosiglitazone (titrated to 8 mg), daily ramipril (titrated to 15 mg), both, or neither. Patients with cardiovascular disease, including heart failure or reduced ejection fraction, were excluded. All patients were encouraged to maintain healthy diets and lifestyles.

After a median 3 years of follow-up, the primary outcome of diabetes or death occurred significantly less often in patients who received rosiglitazone than in those who received placebo (12% vs. 26%); the difference was due entirely to a reduction in incident diabetes. Significantly more rosiglitazone patients than placebo patients regressed to normoglycemia (50% vs. 30%). Ramipril recipients were significantly more likely than placebo recipients to regress to normoglycemia (42% vs. 38%), but a trend toward a lower rate of incident diabetes in patients who received ramipril did not reach statistical significance.

Comment: The effect of rosiglitazone on progression to diabetes is similar to that reported for lifestyle changes and greater than that reported for acarbose or metformin. Rosiglitazone might simply have masked progression to diabetes by reducing hyperglycemia; data collected during the post-trial washout period (but not reported here) will test this hypothesis. Ramipril had only a modest effect on glucose metabolism; a longer or larger trial might have yielded significant results. With regard to preventing end-organ complications, we don’t yet know whether starting these interventions in prediabetic patients is more effective than starting them after progression to overt diabetes.

— Bruce Soloway, MD

Published in Journal Watch General Medicine October 12, 2006

Citation(s):

DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: A randomised controlled trial. Lancet 2006 Sep 23; 368:1096-105.

• Medline abstract (Free)

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

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• Medline abstract (Free)