• Diabetes & Endocrinology Clinical Trials
• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus

The Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects with Type 2 Diabetes [DURATION-6; NCT01029886] trial did not meet the prespecified primary endpoint that once-weekly injections of exenatide were noninferior to daily injections of liraglutide in reducing HbA1C in type 2 diabetes mellitus (T2DM) patients who were treated with lifestyle modification and oral antihyperglycemic medications. John Buse, MD, PhD, University of North Carolina, Chapel Hill, North Carolina, USA, presented results of the trial.

DURATION-6 was an international, multicenter, open-label, randomized trial that was designed to compare injections of once-weekly exenatide, a glucagon-like peptide (GLP-1) receptor agonist, to once-daily liraglutide with regard to glycemic control, body weight, and safety in patients with T2DM. The primary outcome of the study was the change in HbA1C from baseline to treatment endpoint. Noninferiority was concluded if the upper limit of the confidence interval for the treatment difference in change from baseline HbA1C (exenatide − liraglutide) was <0.25%.

Inclusion criteria included a diagnosis of T2DM; suboptimal glycemic control, as evidenced by an HbA1C measurement at the study start of 7.1% to 11.0%; a body mass index ≤45 kg/m²; lifestyle modification (diet and exercise) and treatment with one of the following single oral antihyperglycemic agents or a combination of them, administered at maximum tolerated dose: metformin, sulfonylureas, metformin plus a sulfonylurea, or metformin plus pioglitazone.

Patients were recruited from 19 countries. Average study participant age was 57 years, and approximately 55% was male. The duration of diabetes since diagnosis was approximately 9 years. In addition to the patients' baseline medication of oral antidiabetic drugs, subjects were randomized to receive 2 mg exenatide once weekly (n=461) and a standard-dose titration of liraglutide, beginning at 0.6 mg and ending at 1.8 mg by Week 4 of the study (n=450). The 10-week safety follow-up was performed after the 26-week study.

The mean reduction in HbA1C for patients who were on the once-weekly dosing schedule of exenatide was 1.28% compared with 1.48% in patients who received liraglutide at 1.8 mg daily (p<0.002).

Of the 450 patients who were on liraglutide, 20% complained of nausea compared with 9% of the 461 patients who were on exenatide. Approximately 13% of patients who were on liraglutide experienced diarrhea compared with 6% of those who were on exenatide. Of patients who were on liraglutide, 11% experienced vomiting compared with 4% of those who were on exenatide. Of those who were on exenatide, 10% had injection-site nodules compared with 1% of those who were receiving liraglutide. There were no major hypoglycemia events in either group, and more than 85% of participants in both treatment arms completed the trial.

Dr. Buse concluded his presentation, pointing out that exenatide once weekly and liraglutide once daily provided effective glucose control, modest weight loss, and infrequent hypoglycemic episodes in patients with uncontrolled T2DM. At the doses that were tested, exenatide once weekly had a moderately smaller reduction in HbA1C (treatment difference at study end 0.2%) and weight (treatment difference at study end 0.9 kg) than liraglutide, administered at the maximum dose, but with less frequent gastrointestinal adverse effects. These differences, along with frequency and method of injection, could be used by clinicians in shared decision-making regarding treatment of patients with type 2 diabetes who are uncontrolled on oral antihyperglycemic agents.

• © 2011 MD Conference Express®