GLP-1 Peptides for Weight Loss

Once-monthly GLP-1 confers up to 12.3% weight loss at 28 weeks for adults with obesity

February 12, 2026

Key takeaways:

• Once-monthly PF’3944 conferred significant weight loss for adults with obesity across four dosing regimens.
• The agent will be assessed with once-weekly and once-monthly dosing in separate phase 3 trials.

A once-monthly injectable GLP-1 receptor agonist induced up to 12.3% weight loss at 28 weeks among adults with overweight or obesity, according to topline results from a phase 2b trial.

PF’3944 (Pfizer), previously known as MET-097i, is a fully biased, ultra-long-acting GLP-1 under investigation for the treatment of obesity and other cardiometabolic disorders. The investigational therapy conferred significant weight reductions in four once-weekly dosing groups in the phase 2b VESPER-1 trial. In VESPER-3, investigators examined the safety and efficacy of the drug after switching dosing intervals from once weekly to once monthly.

Participants in VESPER-3 were randomly assigned to one of five treatment arms, with all five groups receiving once-weekly dosing for 12 weeks and then switching to once-monthly dosing for an additional 1 year:

• starting dose of once-weekly 0.4 mg titrated up to once-weekly 0.8 mg and once-monthly 3.2 mg;
• starting dose of once-weekly 0.8 mg titrated up to once-monthly 3.2 mg;
• starting dose of once-weekly 0.4 mg titrated up to once-weekly 0.8 mg, once-weekly 1.2 mg and once-monthly 4.8 mg;
• starting dose of once-weekly 0.6 mg titrated up to once-weekly 1.2 mg and once-monthly 4.8 mg; and
• placebo.

Weight-loss outcomes

At 28 weeks, all four groups receiving PF’3944 achieved greater weight loss than the placebo group. Adults who started the study drug at once-weekly 0.4 mg and titrated up to once-monthly 4.8 mg reached a placebo-adjusted weight loss of 12.3%, according to the efficacy estimand. Those who began with a once-weekly 0.4 mg dose and titrated up to once-monthly 3.2 mg lost 10% of their body weight at 28 weeks.

According to the release, weight loss had yet to plateau at 28 weeks. The groups that began with once-weekly 0.4 mg dosing and titrated up to once-monthly 3.2 mg and once-monthly 4.8 mg will be the dosing regimens included in a phase 3 trial.

Steven B. Heymsfield, MD, FTOS, professor in the department of metabolism and body composition at Pennington Biomedical Research Center in Baton Rouge, Louisiana, said it was important to note that the weight loss conferred by the drug may be greater when the study concludes at 64 weeks. Heymsfield is not involved in the VESPER-3 trial.

“The benchmark now for GLP-1s is magnitude of weight loss,” Heymsfield told Healio. “The magnitude of weight loss at week 28 was not of the same magnitude as other GLP-1s at later time points, hence the importance that weight loss has not plateaued.”

Safety data

PF’3944 had a safety profile similar to other GLP-1 receptor agonists, according to the press release. Most gastrointestinal treatment-emergent adverse events were mild or moderate in nature. There were no cases of severe diarrhea, and no more than one person in each group had a severe case of nausea or vomiting. Five adults discontinued PF’3944 during once-weekly dosing and five participants stopped.