Roche Announces Topline Results for Petrelintide for Weight Management

Roche recently announced positive topline results from its phase 2 ZUPREME-1 (NCT06662539) trial, positioning petrelintide as a potential contender in the evolving field of chronic weight management. Developed as a long-acting amylin analog, petrelintide offers a distinct mechanism of action compared to the currently dominant glucagon-like peptide-1 (GLP-1) receptor agonists. Although GLP-1 therapies primarily reduce body weight by suppressing appetite, amylin analogs mimic the peptide cosecreted with insulin to increase satiety by directly activating amylin receptors and restoring sensitivity to the hormone leptin.^1,2

“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,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a news release.¹ “Therefore, these data reinforce our confidence in petrelintide’s potential to address important unmet medical needs in chronic weight management.”

The investigational therapy is designed for once-weekly subcutaneous administration and has been engineered for high chemical and physical stability at a neutral pH, a characteristic that prevents fibrillation and may facilitate future coformulation with other peptide-based medicines.^1,2

The 42-week ZUPREME-1 trial, which included 493 participants with a mean body mass index of 37 kg/m², demonstrated that petrelintide achieved a mean body weight reduction of up to 10.7% at its highest dose. This result was statistically significant compared to the 1.7% weight loss observed in the placebo cohort.

For pharmacists monitoring patient adherence and outcomes, the trial’s safety data is particularly noteworthy, as petrelintide exhibited a tolerability profile comparable with placebo. Specifically, in the maximally effective treatment arm, there were no reported cases of vomiting and no treatment discontinuations due to gastrointestinal adverse events, which is common adverse effect for GLP-1 therapies. The overall discontinuation rate due to adverse events (AEs) for petrelintide in this arm was 4.8%, nearly identical to the 4.9% reported for placebo.¹

Clinical observations across both the phase 1 and phase 2 trials have highlighted demographic variations in treatment response, with female participants consistently losing considerably more weight than male patients. Despite these efficacy differences, the incidence of gastrointestinal AEs appeared similar between sex. Although nausea was reported, it was primarily mild and tended to dissipate once participants reached their maintenance dose.^1,3

Furthermore, single-digit rates of diarrhea and constipation were consistent with those seen in the placebo group. These findings suggest that petrelintide may offer a more favorable patient experience than some existing weight-loss therapies, potentially supporting long-term treatment adherence.^1,2

As Roche and Zealand Pharma move forward with their global collaboration to codevelop petrelintide, the focus is now shifting toward its potential as both a monotherapy and a combination regimen. Beyond the primary goal of weight reduction, preclinical data has suggested that amylin analogs may assist in the preservation of lean muscle mass, a critical factor in healthy weight loss.^1,2

Pharmacists can expect more data in the near future, with topline results from the ZUPREME-2 (NCT06926842) trial, which evaluates petrelintide in patients with overweight or obesity and type 2 diabetes, slated for release in the second half of 2026. Additionally, a phase 2 trial exploring the combination of petrelintide with CT-388, a dual GLP-1/gastric inhibitory polypeptide receptor agonist, is expected to initiate later in 2026.^1,2

READ MORE: Obesity Management Resource Center

Are you ready to elevate your pharmacy practice? Sign up today for our free Drug Topics newsletter and get the latest drug information, industry trends, and patient care tips straight to your inbox.

REFERENCES

1. Roche announces positive phase II results for petrelintide, an amylin analog developed for people living with overweight and obesity. News release. Roche. March 4, 2026. Accessed March 6, 2026. https://www.roche.com/media/releases/med-cor-2026-03-05

2. Zealand Pharma. Petrelintide. Accessed March 6, 2026. https://www.zealandpharma.com/pipeline/petrelintide/

3. Hesse D, Olsen MB,Griffin J, Hövelmann U, et al. 1773-P: effects of the novel long-acting amylin analogue petrelintide on body weight and waist circumference by sex in a phase 1 trial. Diabetes. 2025;74(Supplement_1):1773-P. doi:https://doi.org/10.2337/db25-1773-P