Roche Reports Positive Phase II Results For Petrelintide, Showing Significant Weight Loss In Obesity Trial

Roche announced positive topline results from the Phase II ZUPREME-1 clinical trial evaluating the investigational drug petrelintide for people living with overweight and obesity. The study compared once-weekly subcutaneous injections of petrelintide with placebo in a total of 493 participants who had an average body mass index (BMI) of 37 kg/m². The trial included a gender-balanced population and focused on assessing weight loss outcomes along with safety and tolerability.

The study successfully met its primary endpoint. Participants receiving petrelintide experienced statistically significant and clinically meaningful weight reduction compared with those receiving placebo after 28 weeks of treatment. The therapy was administered through weekly injections, with the dose gradually increased every four weeks. Across all five treatment groups receiving petrelintide, the results showed notable weight loss compared with the placebo group.

Weight loss effects continued through week 42 of the trial. Participants treated with petrelintide achieved an average weight reduction of up to 10.7% from baseline using the efficacy estimand, while those receiving placebo experienced a 1.7% reduction. In the group that achieved the highest level of weight loss, 98% of participants receiving petrelintide were able to reach the targeted maintenance dose. 

This high completion rate highlighted the favorable tolerability of the treatment and strong adherence to the dosing schedule. Weight reduction measured using the treatment regimen estimand was largely consistent with the efficacy estimand results. The trial also observed that female participants generally lost more weight than male participants.

Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, said that petrelintide produced meaningful weight reduction while maintaining a dosing approach that was well tolerated by participants. He noted that tolerability is an important factor in supporting long-term treatment for people living with obesity. According to him, the results strengthen Roche’s confidence that petrelintide could help address significant unmet medical needs in chronic weight management.

The safety results from the trial also showed a favorable profile for petrelintide. The overall tolerability of the treatment was comparable to placebo, and researchers did not observe any unexpected safety signals. The rate of treatment discontinuation due to adverse events was 4.8% among participants receiving petrelintide in the most effective treatment arm, compared with 4.9% in the placebo group.

The most commonly reported adverse events were related to gastrointestinal symptoms, although the majority of these were mild in severity. The proportion of participants experiencing vomiting in the petrelintide groups was actually lower than in the placebo group, and no cases of vomiting were reported in the treatment arm that produced the greatest weight reduction. Rates of diarrhea and constipation were similar to those observed with placebo and remained in the single-digit range.

Nausea occurred less frequently compared with the earlier 16-week Phase 1b trial of petrelintide, where dose escalation was conducted every two weeks instead of every four weeks. Most cases of nausea were mild, and very few incidents were reported once participants reached the maintenance dose. The overall withdrawal rate from the trial for any reason was 8.4% among participants receiving petrelintide compared with 13.6% in the placebo group.

The final results from the ZUPREME-1 trial, including data from a nine-week safety follow-up period, will be presented at an upcoming medical congress. These findings are expected to help guide the design and structure of future Phase III trials evaluating petrelintide. Roche is also continuing research on the therapy through additional studies. Topline results from the second Phase II trial, known as ZUPREME-2, are expected in the second half of 2026. This study is evaluating petrelintide as a monotherapy in people living with overweight or obesity who also have type 2 diabetes. In addition, another Phase II study exploring the combination of petrelintide with CT-388 is planned to begin later in 2026.

The development of petrelintide is part of Roche’s broader strategy to expand its cardiometabolic portfolio. Alongside its diagnostic capabilities, the company is working to develop solutions that address the complex needs of people living with obesity and related health conditions. Obesity is widely recognized as one of the most significant risk factors for chronic disease worldwide. Projections indicate that by 2035, more than four billion people over half of the global population could be living with overweight or obesity. 

The growing prevalence of obesity is influenced by a combination of genetic, biological, behavioral, environmental, and socioeconomic factors. This rising trend is placing increasing pressure on healthcare systems due to the associated health complications and the impact on quality of life. In 2025, Roche and Zealand Pharma entered into an exclusive collaboration and licensing agreement to jointly develop and commercialize petrelintide as a treatment option for people living with overweight and obesity. This partnership aims to accelerate the development of the therapy and expand its potential to address the global burden of obesity.