A ONCE-WEEKLY investigational amylin analogue produced weight loss of up to 10.7% in adults with overweight or obesity, according to results from the phase 2 ZUPREME 1 trial.<\/p>\n
Petrelintide produced significantly greater reductions in body weight than placebo across all five doses tested at 28 weeks, with weight loss continuing through 42 weeks.<\/p>\n
Testing an Alternative Weight-Loss Pathway<\/p>\n
Petrelintide is a long-acting analogue of amylin, a pancreatic hormone co-secreted with insulin in response to food intake. Amylin signalling contributes to appetite and energy-intake regulation, making the pathway a potential target for obesity treatment<\/p>\n
The randomised, double-blind, placebo-controlled ZUPREME 1 trial investigated 485 adults with overweight or obesity without type 2 diabetes. Participants had a mean age of 47 years, mean BMI of 36.7 kg\/m\u00b2 and mean body weight of 107.1 kg; 53% were women.<\/p>\n
Participants received once-weekly subcutaneous petrelintide at doses of 1.0 mg, 2.5 mg, 5.0 mg, 7.0 mg or 9.0 mg, or placebo, alongside lifestyle intervention.<\/p>\n
Weight Loss Approaches 10% by 28 Weeks<\/p>\n
The primary endpoint was percentage change in body weight at Week 28.<\/p>\n
Mean weight reductions were 7.9% with both 1.0 mg and 2.5 mg petrelintide, 9.8% with 5.0 mg, 9.3% with 7.0 mg and 9.4% with 9.0 mg, compared with 1.7% with placebo. The greatest placebo-adjusted reduction, 8.1 percentage points, was therefore observed with the 5.0 mg dose.<\/p>\n
Weight loss continued beyond the primary endpoint. By Week 42, mean reductions reached 8.7%, 9.2%, 10.7%, 10.5% and 10.2% across the five ascending petrelintide doses, respectively, compared with 1.7% for placebo under the efficacy estimand.<\/p>\n
The results suggest that increasing the dose beyond 5.0 mg did not produce substantially greater weight loss in this trial.<\/p>\n
Nausea Most Common Adverse Event<\/p>\n
Nausea was the most frequently reported adverse event, affecting 79 of 404 participants receiving petrelintide (20%) compared with five of 81 (6%) receiving placebo.<\/p>\n
Vomiting occurred in 3% and 6%, respectively, while diarrhoea affected 7% in both groups. Constipation was reported in 7% of petrelintide recipients and 4% receiving placebo.<\/p>\n
Overall serious adverse-event rates were similar between groups. However, independent experts highlighted three serious events considered related to petrelintide: two cases of gallstones and one case of obstructive pancreatitis.<\/p>\n
Larger Trials Needed<\/p>\n
The results support further investigation of amylin-based therapies as another pharmacological approach to chronic weight management.<\/p>\n
However, comparisons with established GLP-1 receptor agonists should be made cautiously. ZUPREME 1 did not directly compare petrelintide with a GLP-1-based treatment, meaning the study cannot establish whether petrelintide offers superior tolerability or treatment persistence.<\/p>\n
The drug also remains investigational. Larger and longer phase 3 studies will be needed to establish its long-term efficacy and safety and determine how it might fit alongside existing obesity treatments.<\/p>\n
Importantly for diabetes specialists, ZUPREME 1 excluded people with type 2 diabetes. Petrelintide is being investigated separately in people with overweight or obesity and type 2 diabetes in the ZUPREME 2 programme.<\/p>\n
Reference<\/p>\n
Garvey WT et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2026. doi:10.1016\/S2213-8587(26)00213-5.<\/p>\n
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