New Weight Loss Jab Petrelintide May Have Fewer Side Effects Than Wegovy and Mounjaro
Adults taking the experimental once-weekly amylin injection petrelintide lost an average of 10% of their body weight over 42 weeks during a Phase 2 trial, compared to a 2% reduction on a placebo, according to results published in The Lancet Diabetes & Endocrinology and presented at the European Association for the Study of Diabetes conference in Milan. The drug, developed by pharmaceutical companies Roche and Zealand, triggered nausea in 20% of participants, while 3% vomited.
Phase 2 Trial Data Show Peak Weight Loss at Mid-Dose Cohorts
The 485-patient trial evaluated five distinct weekly dosage levels of petrelintide—1.0 mg, 2.5 mg, 5.0 mg, 7.0 mg, and 9.0 mg—alongside lifestyle counseling across study sites in the United States, Poland, and Romania, as detailed by SOURCE 2 and SOURCE 4. Primary endpoint data evaluated at Week 28 revealed that the middle dose generated the strongest average reduction. Mean weight loss in the 1 mg and 2.5 mg arms reached 7.9%, climbing to 9.8% on the 5 mg dose. Higher doses failed to increase efficacy significantly; cohorts receiving 7 mg and 9 mg experienced mean reductions of 9.3% and 9.4% respectively at Week 28. By Week 42, mean weight reductions ranged from 8.7% to 10.7% across active treatment groups, versus 1.7% for the placebo group.
When evaluated using treatment policy estimators that account for patient discontinuations, Zealand reported mean weight reductions from baseline to Week 42 of up to 10.2%, compared to 1.4% for the placebo arm. Between 88% and 98% of participants successfully reached their assigned target dose during the trial.
Tolerability Profiles and Comparison with Incretin-Based Jabs
Gastrointestinal side effects, the primary driver behind patient dropouts in existing obesity treatments, occurred at lower rates in the petrelintide trial than those typically documented in clinical evaluations for blockbuster incretin-based medications such as Wegovy and Mounjaro. The Sun reported that 20% of petrelintide participants felt sick, 3% actually vomited, and 7% experienced diarrhea or constipation. By comparison, data from a separate 2025 study cited by sources show that older GLP-1 therapies frequently trigger nausea in up to 44% of patients and vomiting in 18%, with diarrhea and constipation affecting between 24% and 28% of users.
Despite these favorable tolerability metrics, independent researchers noted methodological distinctions in the data. Dr. Marie Spreckley of the University of Cambridge cautioned that because the trial did not execute a direct head-to-head comparison against GLP-1 medicines, direct inferences regarding superior tolerability remain limited. SOURCE 5 noted that trial participants taking petrelintide experienced specific serious adverse events related to the intervention, including two cases of gallstones and one case of obstructive pancreatitis.
Timeline for Confirmatory Phase 3 Studies and Market Entry
Roche is scheduled to initiate three Phase 3 clinical trials to determine if petrelintide works as a monotherapy across three specific patient populations: individuals with obesity or overweight; individuals with obesity or overweight plus Type 2 diabetes; and individuals with obesity or overweight plus cardiovascular disease. The obesity and diabetes trials carry primary completion targets in late 2028, with companion data from the ZUPREME-2 trial expected in the second half of 2026. No commercial pricing, regulatory approval date, or public health service reimbursement schedule has been established.
Concurrently, BMO Capital Markets analysts noted in investor commentary that if confirmatory trials replicate current safety outcomes, amylin agonists could establish a new treatment paradigm prioritizing non-incretin monotherapies as a first-line option for chronic weight management.
