Quick Summary
- Significant Weight Loss: Participants treated with petrelintide achieved a statistically significant 10.7% mean body weight reduction over 42 weeks, compared to just 1.7% for the placebo group.
- Superior Tolerability: The trial reported a “placebo-like” safety profile, with no cases of vomiting in the highest dose group and zero treatment discontinuations due to gastrointestinal issues—a major differentiator from existing GLP-1 therapies.
- A Promising Non-GLP-1 Alternative: As a long-acting amylin analog, petrelintide offers a new pathway for chronic weight management that focuses on satiety with minimal side effects, potentially preserving better muscle-to-fat ratios.
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced positive topline results from the Phase II ZUPREME-1 clinical trial, evaluating the efficacy and safety of petrelintide, an investigational long-acting amylin analog, in individuals living with overweight and obesity.
The trial successfully met its primary endpoint, demonstrating that participants treated with petrelintide achieved a statistically significant and clinically meaningful reduction in body weight compared to those receiving a placebo.
Significant Weight Reduction and Sustained Efficacy
The ZUPREME-1 study involved 493 participants with a mean BMI of 37 kg/m². Data showed that once-weekly subcutaneous injections of petrelintide resulted in up to 10.7% mean body weight reduction at week 42, compared to just 1.7% for the placebo group (p-value < 0.001).
Notably, weight loss was observed across all five treatment arms of the study. The results underscore petrelintide’s potential as a potent monotherapy for long-term weight management, with efficacy levels that rival established treatments in the metabolic space.
Exceptional Tolerability Profile
One of the most significant findings from the Phase II data is petrelintide’s “placebo-like” tolerability. Unlike many existing incretin-based therapies (such as GLP-1 receptor agonists) that often cause significant gastrointestinal distress, petrelintide showed:
- No cases of vomiting in the maximally effective dose group.
- Zero treatment discontinuations due to gastrointestinal adverse events in the highest dose cohort.
- Low rates of nausea, with the vast majority of cases reported as mild and occurring primarily during the dose-escalation phase.
Petrelintide achieved meaningful weight loss with a well-tolerated dosing approach, which is essential to support long-term and sustained benefits for people living with obesity,
These data reinforce our confidence in petrelintide’s potential to address important unmet medical needs.
Levi Garraway, Roche’s Chief Medical Officer
The Mechanism: A New Pathway for Obesity
Petrelintide operates as a long-acting amylin analog. Amylin is a hormone co-secreted with insulin that induces satiety and slows gastric emptying. By targeting the amylin pathway rather than GLP-1, Roche aims to provide a high-quality weight loss experience with fewer side effects, potentially preserving more lean muscle mass a critical factor in metabolic health.
Future Outlook and Development
Following these positive results, Roche plans to move forward with Phase III clinical trial designs. The company is also currently conducting the ZUPREME-2 trial, evaluating petrelintide in patients with type 2 diabetes, with results expected in the second half of 2026. Additionally, a study exploring the combination of petrelintide with Roche’s dual GLP-1/GIP receptor agonist, CT-388, is slated to begin later this year.
Detailed data from the ZUPREME-1 trial will be presented at an upcoming medical congress to further inform the global medical community on this promising new therapeutic option.
Study Design & Participant Demographics
The trial was designed to evaluate the efficacy and safety of five different dose levels of once-weekly petrelintide over a 42-week treatment period.
| Feature | Detail |
| Total Enrollment | 493 participants |
| Study Locations | 33 sites across the United States, Poland, and Romania |
| Mean Age | 48 years |
| Mean BMI | 37 kg/m² |
| Mean Baseline Weight | 107 kg |
| Gender Balance | 53% Female / 47% Male |
| Intervention | 5 doses of once-weekly subcutaneous petrelintide + reduced-calorie diet & exercise |
| Dose Escalation | Escalated every 4th week (up to 16 weeks) |
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Primary & Secondary Efficacy Endpoints
The trial met its primary endpoint at 28 weeks and sustained weight loss through the end of the treatment period at 42 weeks.
- Primary Endpoint (Week 28): Achieved statistically significant and clinically meaningful weight loss from baseline in all five petrelintide treatment arms compared to placebo.
- Secondary Endpoint (Week 42 – Efficacy Estimand):
- Petrelintide (Highest Dose): 10.7% mean body weight reduction.
- Placebo: 1.7% mean body weight reduction.
- P-value: < 0.001 (indicating high statistical significance).
- Demographic Insights: Female participants achieved considerably higher weight loss compared to male participants. Analysts estimated that, if the trial were 80% female (similar to some competitor trials), the weight-loss figure would have been approximately 12.5%.
Safety and Tolerability Data
The standout feature of the ZUPREME-1 trial was petrelintide’s “placebo-like” safety profile, which contrasts sharply with the high GI side effects seen in GLP-1 therapies.
| Metric | Petrelintide (Max Dose) | Placebo |
| AE Discontinuation Rate | 4.8% | 4.9% |
| Total Trial Withdrawal | 8.4% | 13.6% |
| Adherence (reaching maintenance dose) | 98% | N/A |
| Vomiting Cases | 0% | Similar to a placebo |
| Nausea Profile | Primarily mild; mostly during escalation | Similar to placebo |
| Diarrhea & Constipation | Single-digit rates | Consistent with placebo |
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