Setmelanotide delivers long-term benefits in adults with obesity

The melanocortin-4 receptor agonist setmelanotide has demonstrated long-term clinical benefit and an acceptable safety profile in adults with monogenic or syndromic obesity, reports a study.

Seventeen patients with obesity due to Bardet–Biedl syndrome (BBS; n=11) or biallelic variants in leptin receptor (n=4) or pro-opiomelanocortin (POMC; n=2) were included in this ongoing prospective monocentric cohort study. Participants either initiated setmelanotide in routine care between 2022 and 2024 or continued therapy after participating in the RM-493-022 clinical trial.

The mean follow-up time was 14.4 months. Within the first year of treatment, patients showed a clinically significant weight reduction of 20 percent from their highest pretreatment weight. Those who received prior treatment in a clinical trial maintained their weight loss over time.

Eating behaviour among participants also improved, with significant reductions in hunger (–62 percent), food craving (–41 percent), and external eating evaluated by DEBQ. Overall, the safety profile of setmelanotide was consistent with data from phase III trials, with no new safety signals.

"The melanocortin-4 receptor agonist setmelanotide has demonstrated effectiveness in phase III clinical trials for patients with monogenic obesity caused by biallelic variants in the leptin receptor and POMC, as well as for individuals with BBS,” the researchers said. “However, real-world evidence remains limited.”