At week 28, the primary end point, mean weight change, ranged from –7.9% to –9.8% with petrelintide vs –1.7% with placebo (P < .0001 for all comparisons). By week 42, reductions reached –8.7% to –10.7%, while the placebo showed no further change. The 5.0-mg, 7.0-mg, and 9.0-mg doses produced similar results, which the authors said suggests a plateau. At week 42, 34% to 56% of participants receiving petrelintide lost at least 10% of body weight vs 9% with placebo; week 42 end points were exploratory.1
Nausea Was the Main GI Signal
Nausea occurred in 20% of participants receiving petrelintide vs 6% with placebo; 80% of cases were mild, and 73% occurred during dose escalation. Rates of diarrhea (7% vs 7%) and constipation (7% vs 4%) were low, and vomiting was infrequent overall (3% vs 6%), although the 9.0-mg group reached 9%. Just 1% of participants permanently discontinued petrelintide due to GI events, 2% required dose reductions, and 88% to 98% reached their target maintenance dose.1
For pharmacists, the profile points to escalation-phase nausea as the key counseling focus. Other signals included anti-petrelintide antibodies in 38% of treated participants, with no apparent effect on weight loss, and alopecia in 5% vs 1% with placebo. Three serious adverse events were considered treatment related: 2 cases of cholelithiasis and 1 of obstructive pancreatitis. No deaths occurred.1
Cardiometabolic Effects and Limitations
Petrelintide was associated with reductions in high-sensitivity C-reactive protein of up to 41% vs 6% with placebo, systolic blood pressure reductions of 2.8 to 4.0 mm Hg, and greater high-density lipoprotein cholesterol increases. Reductions in triglycerides and low-density lipoprotein cholesterol were largely similar to placebo, and several of these analyses were post hoc. Pulse rate decreased slightly, in contrast to increases typically seen with GLP-1 RAs.1
The population was 86% White, only 4% had a BMI between 27 and 30 kg/m², and dose groups were not masked from one another. The authors cautioned against cross-trial comparisons, noting that weight loss was similar to the 11.5% reported with cagrilintide after 68 weeks.1,3
The study authors noted that it remains an open question whether amylin–GLP-1 combinations improve tolerability over GLP-1 monotherapy but wrote that “amylin-based therapies might have a future as individual as well as combination therapies.” Petrelintide will advance to phase 3 evaluation.1,2
