NEW YORK (Reuters Health) – Diabetes incidence falls during rosiglitazone treatment but returns to baseline after rosiglitazone withdrawal, according to the preprint version of a study that is to be published in the June issue of Diabetes Care.

“These washout results, which show no long-lasting benefit with respect to prevention of diabetes, do not have any impact on the controversy over rosiglitazone use,” Dr. Rury R. Holman from McMaster University, Hamilton, Ontario, Canada told Reuters Health in an email.

Dr. Holman and colleagues examined the impact of withdrawing rosiglitazone and ramipril medication on type 2 diabetes incidence after closeout of the Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial.

At the end of DREAM, participants allocated to rosiglitazone and participants allocated to ramipril had lower fasting and 2-hour postchallenge plasma glucose values and lower systolic and diastolic blood pressures than participants allocated to placebo.

At the end of the trial, significantly fewer rosiglitazone subjects (11.7%) than placebo subjects (26.0%) had new-onset diabetes, but there was no significant difference in diabetes incidence between ramipril (18.2%) and placebo (19.6%) subjects.

Results were similar when the trial and the washout period were considered together.

When the analysis was limited to the washout period, however, there was no significant difference in new-onset diabetes rates between rosiglitazone (10.6%) and placebo (9.8%) or between ramipril (10.6%) and placebo (9.7%).

Similarly, fasting plasma glucose levels did not differ between rosiglitazone and placebo subjects (or between ramipril and placebo subjects) at the end of the washout. Two-hour postchallenge median plasma glucose levels at the end of washout did not differ between ramipril and placebo subjects but were significantly lower in the rosiglitazone subjects than in the placebo subjects.

“Some people had expected that rosiglitazone might alter the natural history of diabetes given the earlier encouraging post-washout data seen in women with gestational diabetes given troglitazone in the Buchanan study and the slightly slower increase in glycaemia over time seen in people with recently diagnosed diabetes in the ADOPT study with rosiglitazone, compared with glibenclamide,” Dr. Holman said. “The DPP, however, like DREAM, did not show a sustained post-washout glycemic benefit.”

“It is important to perform well-conducted washout studies when evaluating therapies designed to delay or prevent the onset of diabetes to better understand the mechanism(s) involved in the event that they are successful,” Dr. Holman concluded.

DREAM was funded by GlaxoSmithKline and sanofi-aventis, among others, which also provided consulting and lecture fees to several of the authors. Four of the authors have also assigned their patent for the use of ramipril to prevent diabetes to sanofi-aventis.

Diabetes Care 22 April 2011.