Once-Monthly MariTide Shows Promising Weight Loss in Obesity and Type 2 Diabetes: Phase 2 Trial

MariTide is designed to combine the effects of glucagon-like peptide-1 (GLP-1) receptor activation with glucose-dependent insulinotropic polypeptide (GIP) receptor antagonism. This unique mechanism targets key metabolic pathways involved in appetite regulation, insulin sensitivity, and weight management.

The study enrolled a total of 592 adults, divided into two cohorts: individuals with obesity (465 participants) and those with both obesity and type 2 diabetes (127 participants). Participants were randomized to receive various dosing regimens of maridebart cafraglutide or a placebo injection over a year. Doses ranged from 140 mg to 420 mg, administered every four or eight weeks, with some groups undergoing dose escalation to evaluate tolerability.

The study revealed the following findings:

• In the obesity-only cohort, participants lost an average of 12.3% to 16.2% of their baseline body weight over 52 weeks, depending on the dosing regimen, compared to just 2.5% in the placebo group.
• The greatest weight reduction was observed in participants receiving 420 mg of maridebart cafraglutide every four weeks.
• Among individuals with both obesity and type 2 diabetes, average weight loss ranged from 8.4% to 12.3% at week 52, while the placebo group showed only a 1.7% weight reduction.
• Participants with obesity and diabetes also experienced significant improvements in blood sugar control, with HbA1c levels dropping by 1.2 to 1.6 percentage points, in contrast to a 0.1-point reduction in the placebo group.
• Gastrointestinal adverse events such as nausea and diarrhea were frequently reported but occurred less often and with lower intensity among those who received dose-escalation or lower starting doses.
• The trial did not report any new or unexpected safety concerns, reinforcing the overall tolerability of the treatment.

The authors wrote, "Overall, the trial findings suggest that maridebart cafraglutide, administered once a month, has the potential to become an effective therapeutic option for weight management in adults with or without type 2 diabetes. The substantial and sustained weight reduction, along with improvements in blood sugar levels, marks a promising advance in the treatment landscape for obesity."

"Further research, including larger phase 3 trials, will be essential to confirm long-term safety and effectiveness before regulatory approval," they concluded.

Reference:

Jastreboff AM, Ryan DH, Bays HE, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial. N Engl J Med. 2025;Epub ahead of print.