Once-monthly cafraglutide helps with weight loss in adults with obesity

Once-a-month treatment with maridebart cafraglutide—a long-acting peptide–antibody conjugate that combines glucagon-like peptide-1 receptor agonism and glucose-dependent insulinotropic polypeptide receptor antagonism—results in substantial weight reduction in patients with obesity with or without type 2 diabetes, according to a phase II study.

The study included 592 participants with obesity, of which 127 had type 2 diabetes (obesity–T2D cohort: mean age 55.1 years, 42 percent female, mean BMI 36.5 kg/m²) and 465 had no T2D (obesity cohort: mean age 47.9 years, 63 percent female, mean BMI 37.9 kg/m²).

Participants in the obesity cohort were randomly assigned to receive maridebart cafraglutide subcutaneously at a dose of 140, 280, or 420 mg every 4 weeks without dose escalation; 420 mg every 8 weeks without dose escalation; 420 mg every 4 weeks with 4-week dose escalation; 420 mg every 4 weeks with 12-week dose escalation; or placebo. Participants in the obesity–T2D cohort were randomly assigned to receive maridebart cafraglutide at a dose of 140, 280, or 420 mg every 4 weeks (all without dose escalation) or placebo.

The primary endpoint of the percent change in body weight at week 52 in the obesity cohort ranged from −12.3 percent (95 percent confidence interval [CI], −15.0 to −9.7) to −16.2 percent (95 percent CI, −18.9 to −13.5) with maridebart cafraglutide vs −2.5 percent (95 percent CI, −4.2 to −0.7) with placebo.

In the obesity–T2D cohort, the percent change in body weight at week 52 ranged from −8.4 percent (95 percent CI, −11.0 to −5.7) to −12.3 percent (95 percent CI, −15.3 to −9.2) with maridebart cafraglutide vs −1.7 percent (95 percent CI, −2.9 to −0.6) with placebo. Glycated haemoglobin levels decreased by a mean of 1.2 to 1.6 percentage points with maridebart cafraglutide groups but increased by a mean of 0.1 percentage point with placebo.

In terms of safety, gastrointestinal adverse events were common with maridebart cafraglutide, although they occurred less frequently with dose escalation and a lower starting dose. No unexpected safety signals were documented.