Dulaglutide 1.5 mg (Trulicity, Eli Lilly) plus a sulfonylurea appears to be significantly more effective than a sulfonylurea alone in lowering HbA1c in patients with diabetes after 24 weeks of treatment, according to new data from the AWARD-8 trial presented at the World Diabetes Congress.
“This was the first study examining the efficacy of dulaglutide vs placebo on a background of sulfonylurea monotherapy. The results were consistent with previous data from the dulaglutide clinical trials program with respect to glucose control, with a robust 1.3% between-group difference. Thus, while the study was novel and necessary, it was not unexpected,” said lead study researcher Kathleen Dungan, MD, an associate professor at The Ohio State University Wexner Medical Center in Columbus.
“Further, it is of interest to observe how background therapy can influence effects on weight and hypoglycemia.”
This phase 3, randomized, double-blind, placebo-controlled study compared the efficacy and safety in 299 patients with type 2 diabetes and a mean baseline HbA1c of 8.4%.
At the primary end point of 24 weeks, dulaglutide plus a sulfonylurea was found to be superior to a sulfonylurea plus placebo for HbA1c reduction from baseline (–1.38% vs –0.11%). The study also demonstrated that significantly more patients in the dulaglutide plus a sulfonylurea arm achieved an HbA1c of less than 7% (55.3%) compared with a sulfonylurea plus placebo (18.9%).
The researchers also found that dulaglutide plus a sulfonylurea significantly reduced fasting serum glucose levels compared with a sulfonylurea plus placebo (–30.60 mg/dL vs +2.93 mg/dL).
The most commonly reported adverse events were gastrointestinal-related and consistent with prior studies. There were no cases of pancreatitis or pancreatic cancer in either treatment group.
As expected, more patients treated in the dulaglutide plus a sulfonylurea arm experienced episodes of hypoglycemia compared with those treated with a sulfonylurea alone, though the overall incidence of documented symptomatic hypoglycemia was low (11.3% in the dulaglutide arm).
“The most common side effects were gastrointestinal in nature, approximately 20%, and included nausea, diarrhea, and eructation. This is clinically relevant, but it is important to emphasize that gastrointestinal side effects were mild to moderate and transient in the majority of patients,” Dr Dungan told Endocrinology Advisor.
There were no reported cases of severe hypoglycemia in either group.
As a secondary end point of the study, dulaglutide plus a sulfonylurea was associated with weight reduction from baseline (-0.91 kg), though the difference compared with a sulfonylurea plus placebo did not reach statistical significance.
The findings affirm that this agent is efficacious and well-tolerated as an add-on to sulfonylurea therapy, according to Dr Dungan.
“This study was 24 weeks, which was fairly short but sufficient to answer the question at hand. Long-term studies are needed and the long-term cardiovascular endpoint trial for dulaglutide (REWIND) currently under way will provide additional long-term safety data,” he said.
Disclosure: This trial was sponsored by Eli Lilly and Company.
- Dungan K, Weitgasser R, Manghi FP, et al. Abstract 0219-PD. Efficacy and safety of once weekly dulaglutide added on to sulfonylurea in type 2 diabetes (award-8). Presented at the World Diabetes Congress; November 30-December 4, 2015; Vancouver, Canada.