Roche reports positive Phase II ZUPREME-1 results showing once-weekly petrelintide achieved up to 10.7% weight loss with favourable tolerability in adults with overweight or obesity.
Written By: Chikkula Pavan Kumar, Pharm.D.
Reviewed By: Pharmacally Editorial Team
Roche announced positive topline results from the Phase II ZUPREME-1 trial evaluating investigational amylin analog petrelintide in people living with overweight and obesity. The randomized, double-blind, placebo-controlled study enrolled 493 participants with a mean body mass index (BMI) of 37 kg/m² and met its primary endpoint, demonstrating statistically significant and clinically meaningful weight loss at 28 weeks with once-weekly subcutaneous petrelintide compared with placebo.
Weight reduction was sustained through week 42, with participants achieving up to 10.7% mean weight loss from baseline using the efficacy estimand, compared with 1.7% with placebo. In the cohort showing the greatest weight reduction, 98% of participants reached the maintenance dose, highlighting strong tolerability. Female participants experienced greater weight loss than male participants in the trial.
“Petrelintide achieved meaningful weight loss with a well-tolerated dosing approach, which is essential to support long-term and sustained benefits in people living with obesity,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, noting that the results strengthen confidence in petrelintide’s potential for chronic weight management.
Petrelintide demonstrated a favorable safety profile comparable to placebo, with no unexpected safety signals reported. Discontinuation due to adverse events occurred in 4.8% of patients in the maximally effective treatment arm versus 4.9% with placebo.
The most common adverse events were mild gastrointestinal effects. Vomiting occurred less frequently than with placebo and was absent in the highest-efficacy treatment arm, while rates of diarrhea and constipation remained in the single-digit range. Nausea was less frequent than in the earlier Phase 1b study and was mostly mild, with almost no cases reported after patients reached maintenance dosing.
Full results from ZUPREME-1 (NCT06662539), including a nine-week safety follow-up, will be presented at an upcoming medical meeting and will guide the design of future Phase III trials. A second Phase II trial, ZUPREME-2, evaluating petrelintide in people with overweight or obesity and type 2 diabetes, is expected to report topline results in the second half of 2026.
Roche also plans to initiate a Phase II study in 2026 exploring petrelintide in combination with CT-388.
Petrelintide is a long-acting amylin analog designed for once-weekly subcutaneous administration. Amylin, a hormone co-secreted with insulin from pancreatic beta cells, regulates appetite and satiety. By activating amylin receptors and restoring sensitivity to the satiety hormone leptin, the therapy may help reduce food intake and promote sustained weight loss.
While most currently approved obesity medicines target the GLP-1 or GLP-1/GIP pathways, amylin-based therapies are emerging as a new class of metabolic treatments. Amylin analogs such as petrelintide aim to enhance satiety signaling and may offer complementary mechanisms to GLP-1 therapies. Several programs are currently under development, including Novo Nordisk’s cagrilintide-based combination CagriSema, highlighting growing industry interest in multi-hormone approaches for chronic weight management.
The petrelintide is being developed under a 2025 collaboration between Roche and Zealand Pharma to co-develop and commercialize petrelintide for obesity and overweight. The program forms part of Roche’s expanding cardiometabolic portfolio aimed at addressing the growing global burden of obesity and its associated comorbidities.
Reference
Roche announces positive Phase II results for petrelintide, an amylin analog developed for people living with overweight and obesity, 05 March 2026, Roche announces positive Phase II results for petrelintide, an amylin analog developed for people living with overweight and obesity
Once-weekly Petrelintide Versus Placebo for Obesity or Overweight With Co-morbidities (ZUPREME), ClinicalTrials.gov ID NCT06662539, https://clinicaltrials.gov/study/NCT06662539
About Writer
Chikkula Pavan Kumar, Pharm.D.
He is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.