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Once-Weekly Exenatide Similar to Daily Metformin in Monotherapy for Type 2 Diabetes

Jan 19, 2012

A direct comparison of four agents as monotherapy in drug-naive patients with type 2 diabetes shows that exenatide once-weekly, metformin, and pioglitazone provide good improvement in glycemic control, while sitagliptin is less effective.

Dr. Marilyn K. Boardman at Eli Lilly and Company, Indianapolis, Indiana, and colleagues in Minnesota, the UK, Germany, and India commented that, the different agents are associated with significantly different changes in body weight, according to the published study and “head-to-head comparative studies are needed to better inform treatment decisions for type 2 diabetes, a disease for which there are numerous treatment options.”

Dr. Boardman and colleagues conducted a 26-week double-blind trial to evaluate the efficacy and safety of subcutaneous exenatide once weekly 2.0 mg, in comparison with metformin 2000 mg/d, pioglitazone 45 mg/d, and sitagliptin 100 mg/d monotherapy, in 820 intent-to-treat drug-naive patients with type 2 diabetes. The participants were given weekly placebo injections or daily placebo oral medication as appropriate to maintain blinding.

Baseline average hemoglobin A1c (HbA1c) was 8.5% and mean body weight was 87.0 kg, according to the report. After 26 weeks, absolute changes in HbA1c were -1.53% with exenatide once weekly, -1.48% with metformin, -1.63% with pioglitazone, and -1.15% with sitagliptin, the team reports.

Exenatide was non-inferior to metformin, but not pioglitazone, and superior to sitagliptin. As the researchers point out, the first three agents all achieved a target HbA1c concentrations of less than 7%.

Weight changes in the four treatment arms were -2.0 kg with exenatide once weekly and metformin, +1.5 kg with pioglitazone, and -0.8 kg with sitagliptin, the report indicates.

The investigators saw no unexpected findings in terms of safety or tolerability.

“The similar effects obtained with EQW (exenatide once weekly) monotherapy and MET (metformin) monotherapy in terms of HbA1c and body weight reductions support the appropriateness of considering MET as the first-line antihyperglycemic agent in type 2 diabetes,” the researchers conclude.

Published online before print December 30, 2011, doi: 10.2337/dc11-1107 Diabetes Care December 30, 2011