Once-weekly amylin analog petrelintide produced up to 9.2% weight loss at 28 weeks in adults with obesity and type 2 diabetes, Zealand Pharma reports.
Zealand Pharma reported topline results from the phase 2b ZUPREME-2 trial, in which once-weekly petrelintide, an investigational amylin analog, met its primary endpoint of body weight reduction at 28 weeks in adults with overweight or obesity and type 2 diabetes.1
The data arrive as the company and its licensing partner, Roche, begin a phase 3a program expected to enroll about 7,000 participants.1
“These results further support the potential of petrelintide in chronic weight management and, for the first time, demonstrate its promise as a standalone treatment for those living with overweight or obesity and type 2 diabetes,” said David Kendall, MD, Chief Medical Officer at Zealand Pharma. “These data confirm the potential for clinically meaningful weight reduction with a promising and favorable tolerability profile. We are also encouraged by the improvements in glycemic control — a combination essential for supporting long-term, sustained benefits in people living with obesity and type 2 diabetes. Together with Roche, we look forward to investigating petrelintide in our recently initiated Phase 3 registrational program to address important unmet medical needs in chronic weight management.”1
ZUPREME-2 was a randomized, double-blind, placebo-controlled, multicenter study that enrolled 220 U.S. participants taking metformin, with or without a sodium-glucose cotransporter 2 inhibitor.1 Mean baseline body mass index was 36.3 kg/m², and mean baseline glycated hemoglobin (HbA1c) was 8.0%.1
Three once-weekly doses were compared with placebo, each added to a reduced-calorie diet and increased physical activity, with dose escalation every fourth week for up to 16 weeks and maintenance through week 28.1
All three petrelintide arms produced statistically significant weight reductions versus placebo at week 28. Mean loss ranged from 7.4% to 9.2% using the efficacy estimand, compared with 2.0% with placebo, and results were largely consistent under the treatment regimen estimand.1
HbA1c fell by up to 0.65% with petrelintide and rose 0.23% with placebo, a placebo-adjusted reduction of 0.61% to 0.88%.1 Zealand reported no unexpected safety signals.
Gastrointestinal events were the most common adverse events, most of them mild and occurring during dose escalation, and discontinuations because of those events were 1.9% with petrelintide versus 1.7% with placebo.1
Petrelintide is a long-acting human amylin analog designed for weekly subcutaneous injection.1 Amylin is produced in pancreatic beta cells and secreted with insulin after nutrient intake.
According to the company, activating its receptor reduces body weight by restoring sensitivity to the satiety hormone leptin.1 Zealand also says the molecule was designed for chemical and physical stability, with no fibrillation near neutral pH, a property that allows co-formulation with other peptides.1
That attribute bears on development strategy. The partners are also studying petrelintide with Roche's dual incretin receptor agonist enicepatide (CT-388), with a phase 2 combination trial planned to start in the second half of 2026.1
In the phase 2 ZUPREME-1 trial of 493 participants without diabetes, petrelintide produced up to 10.7% mean weight loss at 42 weeks versus 1.7% with placebo.2
People with type 2 diabetes generally lose less weight on obesity therapies than people without the condition.3,4 In the phase 3 STEP 2 trial, semaglutide 2.4 mg produced an estimated 9.6% mean weight reduction versus 3.4% with placebo at 68 weeks.3
In SURMOUNT-2, tirzepatide reduced weight by 12.8% at 10 mg and 14.7% at 15 mg versus 3.2% with placebo at 72 weeks, using the treatment-regimen estimand.4 Cross-trial comparison is limited.
ZUPREME-2 is a 28-week phase 2 study with a smaller population, different analysis conventions and no head-to-head arm, so its figures reflect shorter treatment exposure.
The results are company-reported topline data and have not been peer reviewed. Zealand said full results will be presented at an upcoming scientific conference.1 The announcement does not report secondary endpoints such as the proportion of participants losing at least 5% or 10% of body weight, waist circumference or lipid changes.
The 28-week duration also leaves open how weight loss and tolerability hold over longer follow-up.1 The phase 3a program comprises three trials: ZUPREME-3 in people with obesity or overweight without type 2 diabetes, ZUPREME-4 in those with type 2 diabetes, and ZUPREME-5 in those with established cardiovascular disease.1
The first participants have begun treatment, and the larger populations will test whether the phase 2 findings carry forward.1
Sources
