Once-Monthly Maridebart Cafraglutide in Obesity — A Phase 2 Trial

To the Editor: In a phase 2 trial involving adults with obesity, Jastreboff et al. (Sept. 4 issue) 1 found that treatment with maridebart cafraglutide, a long-acting peptide–antibody conjugate that combines glucagon-like peptide-1 (GLP-1) receptor agonism and glucose-dependent insulinotropic polypeptide (GIP) receptor antagonism, led to substantial weight loss at 52 weeks without participants reaching a weight plateau. GIP receptors are abundant in adipose tissue, and GIP is essential for adipose-tissue synthesis. Moderate de novo lipogenesis in healthy adipose tissue has beneficial metabolic effects and may promote longevity, whereas lipodystrophy is associated with ectopic lipid accumulation in liver and muscle. Long-term treatment . . .