Results from the ADOPT Study

December 4, 2006

by Josh Murphy

In recently-diagnosed type 2 diabetes, initial monotherapy with rosiglitazone (Avandia^® , GlaxoSmithKline) is associated with a significantly slower progression of monotherapy failure compared to metformin (Glucophage^®, Bristol-Myers Squibb) or glyburide (Micronase^®, Pfizer), according to results from the ADOPT (A Diabetes Outcome Progression Trial) study¹.

These findings were presented at the International Diabetes Federation (IDF) 19th Annual World Diabetes Congress in Cape Town and published simultaneously in the New England Journal of Medicine.

ADOPT investigators randomized 4,360 patients age 30-75 years with newly-diagnosed type 2 diabetes and no previous pharmocologic treatment for diabetes to randomized to rosiglitazone 4 mg, metformin 500 mg, or glyburide 2.5 mg daily. Dosages were titrated to maximum effectiveness if fasting plasma glucose exceeded 139 mg/dL. Patients with hepatic or renal disease, angina, or known congestive heart failure (CHF) were excluded.

Monotherapy treatment failure, the primary outcome, was defined as fasting plasma glucose >180 mg/dL. Secondary outcomes included progression to fasting plasma glucose >140 mg/dL.

Median duration of treatment was 4 years in both the rosiglitazone and metformin groups and 3.3 years in the glyburide group. At 5 years, there was a significant 32% relative risk reduction in the primary outcome in patients randomized to rosiglitazone compared to metformin, and a 63% reduction in rosiglitazone compared to glyburide (Figure 1).

Independently-adjudicated treatment failure was reached by 29% of patients in both the rosiglitazone and metformin groups and 22% in the glyburide group. The secondary outcome was reduced by a significant 34% in patients randomized to rosiglitazone compared to metformin and 62% in rosiglitazone compared to glyburide (Figure 2).

At 4 years, significantly more patients in the rosiglitazone group achieved hemoglobin A1c <7% compared to both metformin and glyburide groups (Figure 3). Maximal treatment effect on A1c was reached at 1 year in the rosiglitazone group compared to 4 months in both metformin and glyburide groups.

Tertiary outcomes such as insulin sensitivity and beta cell function improved to a greater extent in the rosiglitazone group, with greater improvement during the first 6 months of treatment and leveling off thereafter. With respect to adverse events, there were a greater number of total cardiovascular events and investigator-reported CHF in the rosiglitazone group (Figures 4 and 5). However, there were no differences in independently-adjudicated CHF between groups (Figure 6).

These results provide evidence that rosiglitazone can slow progression to hyperglycemia to a greater extent than metformin or glyburide monotherapy. “The relative costs of these medications, their profiles of adverse events, and their potential risks and benefits should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes,” investigators conclude.

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