SOUTH SAN FRANCISCO, California – March 6, 2026
Genentech announced positive topline results from the Phase II ZUPREME-1 clinical trial evaluating the investigational drug Petrelintide for chronic weight management in people living with Obesity and overweight. The randomized clinical study demonstrated statistically significant and clinically meaningful weight reduction, with participants achieving up to 10.7% mean body-weight loss at week 42 compared with 1.7% in the placebo group (p<0.001). The once-weekly injectable therapy also showed placebo-like tolerability with minimal gastrointestinal side effects, highlighting its potential as a next-generation treatment for obesity and related metabolic conditions. The results strengthen Genentech’s growing cardiometabolic pipeline and support further development of petrelintide as both a standalone therapy and a potential combination treatment for long-term weight management.
Phase II Trial Shows Significant Weight Reduction and Safety
The ZUPREME-1 Phase II clinical trial enrolled 493 participants living with overweight or obesity, with an average body mass index (BMI) of 37 kg/m² and an average baseline body weight of approximately 107 kilograms. Participants received once-weekly subcutaneous injections of petrelintide with gradual dose escalation every four weeks. The trial met its primary endpoint by demonstrating significant body-weight reduction at 28 weeks across all five treatment arms compared with placebo, with weight loss continuing through week 42. Patients receiving the maximally effective dose achieved up to 10.7% mean body-weight reduction, while the placebo group showed only 1.7% weight loss. Notably, 98% of participants receiving petrelintide successfully reached the maintenance dose, indicating strong treatment adherence and favorable tolerability. The study also revealed differences in treatment response between genders, with female participants experiencing greater average weight reduction than male participants. These findings highlight petrelintide’s potential as an effective pharmacological therapy for long-term obesity management.
Favorable Tolerability Profile Supports Further Development
Beyond its efficacy, petrelintide demonstrated a safety and tolerability profile comparable to placebo, an important factor for therapies intended for chronic disease management. The overall treatment discontinuation rate due to adverse events was 4.8% in the petrelintide group compared with 4.9% for placebo, indicating minimal treatment-related withdrawal. The most commonly reported adverse events were mild gastrointestinal symptoms such as nausea, diarrhea, and constipation, which remained in the single-digit percentage range across treatment groups. Importantly, no vomiting was reported in the maximally effective treatment arm, and there were no treatment discontinuations related to gastrointestinal adverse events. Researchers also observed that nausea rates were lower than those reported in earlier Phase 1b trials, likely due to a more gradual dosing escalation strategy. Furthermore, most nausea events occurred during early treatment stages and almost completely disappeared once patients reached their maintenance dose. These safety findings reinforce the drug’s potential suitability for long-term chronic therapy, an essential requirement for effective obesity management medications.
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Amylin Analog Targets Metabolic Pathways for Weight Control
Petrelintide is an investigational long-acting amylin analog designed for once-weekly subcutaneous administration, representing a promising new mechanism for weight management therapies. Amylin is a hormone produced by pancreatic beta cells and released alongside insulin after food intake. Activation of amylin receptors helps regulate appetite and metabolism by restoring sensitivity to the satiety hormone leptin, enabling individuals to feel full sooner and reduce caloric intake. By mimicking the physiological effects of natural amylin, petrelintide aims to address underlying biological drivers of obesity rather than simply suppressing appetite. The favorable tolerability profile also supports the therapy’s potential use in combination treatments with other metabolic drugs, an approach increasingly being explored to improve long-term weight management outcomes. According to Genentech, additional data from the ZUPREME-1 trial will be presented at an upcoming medical conference, while a second Phase II study, ZUPREME-2, is expected to report results later in 2026. The company is also planning a Phase II trial evaluating a combination of petrelintide with another investigational therapy, further expanding its cardiometabolic research program.
Obesity is currently recognized as one of the most significant global health challenges, with projections indicating that more than four billion people worldwide may be living with overweight or obesity by 2035. The condition is associated with numerous serious health risks, including cardiovascular disease, diabetes, and metabolic disorders. By advancing innovative therapies such as petrelintide, Genentech aims to provide new treatment options capable of addressing the complex biological and metabolic drivers of obesity, helping patients achieve sustainable long-term weight control and improved overall health outcomes.
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Source: Genentech press release
