The Pharmaceutical Journal
Vol 277 No 7430 p683
9 December 2006

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Rosiglitazone monotherapy has lower failure rate in type 2 diabetes than metformin and glibenclamide

People with type 2 diabetes who are treated initially with rosiglitazone have lower monotherapy failure rates at five years compared with patients initially treated with either metformin or glibenclamide.

This is the key finding of ADOPT (a diabetes outcome progression trial), the first long-term study to show that the progressive loss of blood sugar control in type 2 diabetes can be delayed.

In the study of 4,360 patients, rosiglitazone was associated with a cumulative incidence of monotherapy failure at five years of 15 per cent, compared with 21 per cent for metformin and 34 per cent for glibenclamide. This translates to a risk reduction of 32 per cent for rosiglitazone compared with metformin, and 63 per cent compared with glibenclamide (P<0.001 for both).

Rosiglitazone was more effective than metformin or glibenclamide in delaying the progressive loss of blood sugar control, as measured by fasting plasma glucose and glycated haemoglobin levels. Rosiglitazone also improved insulin sensitivity compared with metformin and glibenclamide (P<0.001 for both) and reduced the rate of loss of beta-cell function (P=0.02 against metformin and P<0.001 against glibenclamide).

Results from the double-blind, randomised, controlled study were presented at the International Diabetes Federation’s World Diabetes Congress in Cape Town, and are published in The New England Journal of Medicine (2006;355:2427).

The authors found that glibenclamide was associated with a lower risk of cardiovascular events (including congestive heart failure) than rosiglitazone. Metformin was associated with a similar risk to rosiglitazone. Rosiglitazone was associated with more weight gain and oedema than the other two agents but with fewer gastrointestinal events than metformin and less hypoglycaemia than glibenclamide. A late unexpected finding was rosiglitazone’s association with fractures in women.

Bernard Zinman, one of the study authors, commented that the first-choice agent would still probably be metformin, but that around 15 per cent of patients would not tolerate that choice. He said: “The study clearly provided evidence showing the benefits of rosiglitazone over [glibenclamide] and, indeed, over metformin, in achieving durability. So I think it will change clinical practice and probably people will be using combination therapy early on.”