Experimental Drug Benefits Type 2 Diabetics
Once-weekly dose of exenatide resulted in sustained improvement in A1c.
SAN FRANCISCO—New results from a phase III trial demonstrate that the investigational once-weekly formulation of exenatide, an incretin mimetic agent, provides sustained glucose control and weight loss for at least 52 weeks in patients with type 2 diabetes.
The data, from the DURATION-1 trial, also show that patients on the twice-daily exenatide formulation achieve added control when they switch to the once-weekly formulation. Findings were presented here at the 68th Scientific Sessions of the American Diabetes Association.
John B. Buse, MD, PhD, director of the Diabetes Care Center and chief of the endocrinology division at the University of North Carolina in Chapel Hill, and colleagues elsewhere reported 22-week follow-up results in 241 patients who had completed a 30-week, randomized, open-label trial comparing a once-weekly to twice-daily formulation of exenatide.
Results at 30 weeks showed that subcutaneous injections of exenatide once weekly produced larger improvements in hemoglobin A1c and fasting plasma glucose than twice-daily injections. The twice-daily formulation is FDA-approved as adjunctive therapy in patients who achieve inadequate glycemic control with metformin, sulfonylureas, and thiazolidinediones.
At the start of the trial, the mean A1c for the entire cohort was 8.3% and the mean fasting plasma glucose (FPG) was 169 mg/dL. Patients who entered the follow-up trial remained on exenatide once weekly or switched from the twice-daily formulation to exenatide once weekly for an additional 22 weeks. Subjects who were on thiazolidinediones, sulfonyl-ureas, and/or metformin at the start of the trial were allowed to continue taking two of these medications throughout the trial.
At 52 weeks, patients who had remained on exenatide once-weekly demonstrated sustained improvements in A1c and FPG levels. The group that had switched from twice-daily to once-weekly exenatide had additional improvements in glycemic control that were about the same as patients who had received the once-weekly formulation for the entire 52 weeks.
At the end of the trial, 74% of patients in both groups had achieved an A1c of 7% or less, and 53% achieved the more stringent target of 6.5% or less. Additionally, patients in both groups had lost 8.6 pounds. Clinically significant BP decreases were documented in both cohorts.
No major hypoglycemia episodes occurred with either formulation irrespective of background therapy. Minor hypoglycemic episodes with either formulation were confined to patients who were also being treated with sulfonylureas.
Dr. Buse said he is encouraged by the findings and noted that the superior efficacy of the once-weekly formulation is likely due to its longer half-life. He emphasized, however, that it takes about six weeks for the drug to provide maximal benefit.