Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes

Abstract

The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5years after therapy has been discontinued. The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2h plasma glucose level of ≥7.0mmol/l or ≥11.1mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2h plasma glucose level of <6.1mmol/l and <7.8mmol/l, respectively. After a median of 1.6years after the end of the trial and 4.3years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect. Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.