Pemvidutide

Pemvidutide is an investigational once-weekly injection that activates two receptors instead of one: the GLP-1 receptor, which suppresses appetite, and the glucagon receptor, which increases energy expenditure and mobilizes fat from the liver. It is not approved by the FDA for any use, and it is not available by prescription in the United States.

Most of its published evidence so far is in liver disease rather than weight. IMPACT, a phase 2b trial published in The Lancet in December 2025, randomized 212 patients with biopsy-confirmed MASH and stage F2 or F3 fibrosis to once-weekly pemvidutide at 1.2 mg or 1.8 mg, given without dose titration, or to placebo. At 24 weeks, MASH resolved without worsening fibrosis in 20% on placebo, 58% at 1.2 mg and 52% at 1.8 mg. The second co-primary endpoint, fibrosis improvement without worsening MASH, showed a much narrower separation from placebo.

Two things to keep in perspective. Phase 2b means the trial was sized to find a dose and a signal, not to establish long-term safety or benefit — 212 patients is small, and 24 weeks is short for a disease measured in decades. And a drug that resolves inflammation on biopsy has not yet been shown to prevent cirrhosis, liver failure or death, which are the outcomes that matter.

The glucagon component is the interesting and the uncertain part. Adding glucagon activity may improve liver fat and energy expenditure beyond what GLP-1 alone achieves, but glucagon also raises blood sugar, so the balance between the two receptors has to be right. Whether that translates into approved therapy depends on phase 3 results and on commercial decisions — albiglutide is the cautionary example of good data and no product.

Worth asking your clinician: whether a trial is enrolling near you if you are interested, and what approved options exist for your situation now. Our pipeline tracker and MASH study roundup follow the field, and SYNERGY-NASH covers the tirzepatide comparison.