Once-Monthly Obesity Drug, MariTide, Achieves Weight Loss Up to 16% at 1 Year

A new trial from the 85th Scientific Sessions of the American Diabetes Association (ADA 2025) provides evidence of a once-monthly agent that could be a game-changer for management of obesity and type 2 diabetes.

Results of the phase 2 trial of maridebart cafraglutide, also known as MariTide, indicate use was associated with body weight reductions ranging from 12-16% in obesity to 8.4-12% in type 2 diabetes with obesity. Additionally, secondary outcome measures revealed use could lower HbA1c by up to 1.6 percentage points.

“Once-monthly treatment options for type 2 diabetes have long been sought after, yet elusive,” said lead investigator Ania M. Jastreboff, MD, PhD, professor at Yale School of Medicine and director of the Y-Weight Yale Obesity Research Center. “MariTide has the potential to be a once-monthly treatment option for people with obesity, with and without type 2 diabetes, resulting in substantial weight reduction and robust improvements in glycemia.”

Driven by advances in epidemiology and the therapeutic pipeline, management of obesity has become a hot topic of discussion among medical circles in recent years. Although much of this interest can be attributed to revelations surrounding the benefit of the GLP-1 receptor agonists, namely semaglutide and tirzepatide, the field has shifted its focus to the potential of multiagonist therapeutics.

Developed by Amgen, maridebart cafraglutide is a once-monthly, long-acting peptide–antibody conjugate that combines GLP-1 receptor agonism with GIP receptor antagonism, representing a novel therapeutic mechanism for obesity treatment.

The phase 2, double-blind, randomized, placebo-controlled trial presented by Jastreboff at ADA 2025 was launched in 2023 to examine the safety and efficacy of maridebart cafraglutide in adults with obesity, both with and without type 2 diabetes. The study enrolled 592 participants across 2 cohorts: 465 participants with obesity and 127 with obesity plus type 2 diabetes.

The obesity cohort had a mean age of 47.9 (SD, 12.3) years, 63% were women, 67% were White, and the mean BMI was 37.9 (SD, 7.5) kg/m2. The obesity and diabetes cohort had a mean age of 55.1 (SD, 11.2) years, 42% were female, 68% were White, and the mean BMI was 36.5 (SD, 7.0) kg/m2.

In the obesity cohort, participants were randomly assigned in a 3:3:3:2:2:2:3 ratio to receive maridebart cafraglutide at varying doses and schedules: 140, 280, or 420 mg every 4 weeks without dose escalation; 420 mg every 8 weeks without escalation; or 420 mg every 4 weeks with either a 4-week or 12-week dose escalation period; or placebo. In the obesity–diabetes cohort, participants were randomly assigned in a 1:1:1:1 ratio to receive maridebart cafraglutide at 140, 280, or 420 mg every 4 weeks (all without dose escalation) or placebo.

At week 52, results of the of intention-to-treat analysis indicated patients in the obesity cohort experienced a mean percent weight reduction of 12.3% (95% CI, -15.0 to -9.7) to 16.2% (95% CI, -18.9 to -13.5) with maridebart cafraglutide and to 2.5% (95% CI, -4.2 to -0.7) with placebo.

In the obesity and diabetes cohort, body weight reductions observed with maridebart cafraglutide ranged from 8.4% (95% CI, -11.0 to -5.7) to 12.3% (95% CI, -15.3 to -9.2) compared to 1.7% (95% CI, -2.9 to -0.6) with placebo. Additionally, investigators called attention to reductions in HbA1c ranging from 1.2 (95% CI, -1.7 to -0.7) to 1.6 (95% CI, -1.9 to -1.2) percentage points compared to a 0.1-point increase (95% CI, -0.4 to 0.5) in the placebo group.

References:

Jastreboff AM, Ryan DH, Bays HE, et al. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity — A Phase 2 Trial. The New England Journal of Medicine. Published online June 23, 2025. doi: 10.1056/NEJMoa2504214