Weight loss with dapiglutide similar to placebo for adults with obesity in phase 2a trial
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Key takeaways:
- There was no significant difference in weight loss for adults with obesity receiving dapiglutide vs. placebo.
- Topline results from a phase 1b trial showed higher-dose dapiglutide induced greater weight loss.
A dual GLP-1/GLP-2 receptor agonist did not confer greater body weight reductions for adults with obesity and without diabetes at 12 weeks compared with placebo, according to data from a phase 2a proof-of-concept study.
Dapiglutide (Zealand Pharma) is a once-weekly subcutaneous dual GLP-1/GLP-2 receptor agonist developed to treat obesity. In a phase 1 multiple ascending dose trial, a small group of lean healthy men had a 4.3% decline in body weight at 4 weeks with the novel agent. New findings from the investigator-initiated phase 2a DREAM study presented at the European Association for the Study of Diabetes annual meeting found adults with obesity lost weight with 12 weeks of either 4 mg or 6 mg dapiglutide therapy, but the reductions were similar to those observed in the placebo group. Casper Kjærsgaard Nielsen, MSc, PhD, senior researcher in the center for clinical metabolic research at Gentofte Hospital in Denmark, said the weight loss with placebo was driven in part by several participants who lost between 5 kg and 10 kg of weight during the trial.
“More research is definitely needed,” Nielsen said during the presentation. “Overall, the results suggest that dapiglutide could be beneficial in reducing body weight.”
Nielsen and colleagues enrolled 54 adults aged 18 to 75 years with a BMI of 30 kg/m2 or more and an HbA1c of less than 6.5% who were not taking any anti-obesity medications. Participants were randomly assigned, 1:1:1, to receive 4 mg dapiglutide (mean age, 56 years; 67% women), 6 mg dapiglutide (mean age, 51 years; 56% women) or placebo (mean age, 54 years; 67% women) for 12 weeks. Adults did not participate in lifestyle intervention during the trial. The primary endpoint was change in body weight from baseline to 12 weeks.
No significant difference in weight loss
Adults in all three groups lost weight during the study, with no significant difference between the treatment arms. The 6 mg dapiglutide group had a 4.3% weight reduction at 12 weeks, while the 4 mg dapiglutide group lost a mean 2.9% of body weight and those receiving placebo lost a mean 2.2% of body weight (P = .076), Nielsen said during the presentation.
“Six or seven participants [receiving placebo] had a weight loss of 5 kg or greater relative to baseline,” Nielsen said. “This substantially contributes to the study not meeting its primary endpoint.”
Adults receiving 6 mg dapiglutide had a greater reduction in waist circumference from baseline to 12 weeks compared with the placebo group (unadjusted P = .01), the researchers found. No difference in waist-to-hip ratio change from baseline to 12 weeks was seen between the three groups.
Treatment-emergent adverse events were reported by 94% of participants in the 6 mg dapiglutide group, 83% of those receiving 4 mg dapiglutide and 89% receiving placebo, Most of the adverse events with dapiglutide were gastrointestinal in nature. No participants discontinued the study due to a treatment-emergent adverse event. The only serious adverse event was a death in the 6 mg dapiglutide group, which was due to a primary lung tumor and was unrelated to dapiglutide, Nielsen said.
As vomiting was similar between all three groups, “this leads to the suspicion that the doses might be in the lower therapeutic range in this trial,” he said.
Promise with higher-dose dapiglutide
Studies are underway assessing higher doses of dapiglutide than what were used in the DREAM study. On Sept. 9, Zealand Pharma released top-line results from the first part of a phase 1b multiple ascending dose trial where 54 adults with obesity were randomly assigned to receive up to 13 mg of dapiglutide or placebo for 13 weeks. According to a press release, those receiving dapiglutide lost 6.2% of their body weight from baseline to 13 weeks compared with a 2.1% mean weight gain with placebo.
Part two of the phase 1b trial will increase the dose of dapiglutide up to a maximum of 26 mg and assess the agent over 28 weeks. In the release, Zealand Pharma said it expects to release top-line results from part two of the trial in the first half of 2025 and present detailed data from both parts of the trial at a future conference.
“[The data] give us the confidence needed to rapidly progress dapiglutide into a comprehensive phase 2b trial in people living with overweight and obesity planned for initiation in the first half of 2025,” David Kendall, MD, chief medical officer of Zealand Pharma, said in the release.
Reference:
Zealand Pharma announces positive topline results from 13-week Phase 1b multiple ascending dose clinical trial with GLP-1/GLP-2 receptor dual agonist dapiglutide. https://www.globenewswire.com/news-release/2024/09/09/2943004/0/en/Zealand-Pharma-announces-positive-topline-results-from-13-week-Phase-1b-multiple-ascending-dose-clinical-trial-with-GLP-1-GLP-2-receptor-dual-agonist-dapiglutide.html. Published Sept. 9, 2024. Accessed Sept. 12, 2024.
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Nielsen CK, et al. LBA 07. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid, Spain.
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