Once-weekly exenatide sustains glycemic control, weight loss better than twice-daily regimen

44th Annual Meeting of the EASD

ROME — Exenatide use once weekly provides better glycemic control and is more convenient than the current twice-daily regimen, according to results of the DURATION-1 trial.

John B. Buse, MD, PhD, presented the results of the second half of this 52-week randomized, open-label, non-inferiority trial at the 44th Annual Meeting of the European Association for the Study of Diabetes. Findings from the first 30 weeks were published online this week in The Lancet.

“Improvements in glucose control were observed in those who switched from exenatide (Byetta, Amylin Pharmaceuticals Inc.) twice a day to a new once-weekly formulation,” said Buse, professor, director of the Diabetes Care Center, and chief of the Division of Endocrinology at the University of North Carolina Chapel Hill.

“There was no difference in weight loss at 52 weeks,” he said. “The once-weekly formulation does provide for greater glucose control than twice-daily dosing.”

Reducing frequency

In the first half of the trial, 295 patients were randomized to a 30-week course of either a long-acting release formulation of exenatide 2 mg administered once weekly (n=129), or 10 mcg exenatide twice daily (n=130). The patients had a mean weight of 102 kg and a mean HbA1c of 8.3%. Mean diabetes duration was seven years.

The researchers found that patients given exenatide once weekly saw their HbA1c levels fall to a mean of 6.4% (–1.9%); those on the twice-daily regimen fell to 6.8% (-1.5%). Furthermore, 77% of the patients administered the once-weekly formulation achieved the target HbA1c of ≤7% compared with 61% of the patients on the twice-daily regimen.

In the last 22 weeks of the trial the researchers followed up with 241 patients — 120 from the once-weekly cohort and 121 from the twice-daily cohort. They found that improvements in HbA1c and fasting plasma glucose were sustained in those who received exenatide once weekly (HbA1c, –2%; FPG, –2.6 mmol/L). Those who switched from the twice-daily to once-weekly dosage achieved similar results (HbA1c, –2.0%; FPG, –2.4 mmol/L), according to the abstract. In both groups about equal to 3 in 4 patients achieved HbA1c ≤7%; over half had an HbA1c of ≤6.5%.

Weight loss totaled about 4 kg by week 52 for patients in both groups, according to the abstract.

“The transition was not associated with new or additional adverse events. There were moderate changes in lipids, essentially no change in LDL, HDL and with regards to treatment adverse effects, there were very little cases of nausea and other gastrointestinal effects,” Buse said.

He added that there were no major cases of hypoglycemia observed and no hypoglycemia occurred in patients not using a concomitant sulphonylurea.

In an accompanying comment published in The Lancet, André Scheen, MD, PhD, head of the clinical pharmacology unit at the University of Liège, Belgium, said, “compared with the twice-a-day exenatide regimen, the once-a-week formulation, besides obvious improved ease of use, provided the remarkable advantage of both improved efficacy on glucose control and good gastrointestinal tolerability.” He further suggested that management of type 2 diabetes could change substantially as after confirmation and extension of these findings. – by Tara Grassia

For more information:

Buse J, Drucker D, Taylor K, et al. #146. Exenatide once weekly elicits sustained glycemic control and weight loss over 52 weeks. Presented at: the 44th Annual Meeting of the European Association for the Study of Diabetes; Rome; Sept. 7-11, 2008.

Lancet. 2008;doi:10.1016/S0140-6736(08)61206-4.