NEW YORK (Reuters Health) – 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.

Furthermore, the different agents are associated with significantly different changes in body weight, according to the report in Diabetes Care published online December 30.

“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,” comment Dr. Marilyn K. Boardman at Eli Lilly and Company, Indianapolis, Indiana, and colleagues in Minnesota, the UK, Germany, and India .

They 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 HbA1c was 8.5% and mean body weight was 87.0 kg, according to the report.  After 26 weeks, 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.

As they 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,” Dr. Boardman and colleagues conclude.

Still, they add, “Based on these 26-week data, EQW is a once-weekly dosing option for initial therapy.”

SOURCE:
Efficacy and Safety of Exenatide Once Weekly Versus Metformin, Pioglitazone, and Sitagliptin Used as Monotherapy in Drug-Naive Patients With Type 2 Diabetes (DURATION-4)

Diabetes Care 2012.