What Is Pemvidutide?

1. How does pemvidutide work?

GLP-1 receptor agonism is the familiar half: appetite suppression, slower gastric emptying, and glucose-dependent insulin release, as with semaglutide. The glucagon half is what makes the drug a liver drug. Glucagon receptors are concentrated in the liver, where activation increases fat oxidation and energy expenditure and reduces liver fat directly. Altimmune describes the molecule as balanced, with roughly equal activity at both receptors, against the GLP-1-weighted ratio of the other dual agonist in this class, survodutide. This is also why pemvidutide’s research program is broader than weight loss alone: beyond MASH and obesity, Altimmune has tested it in alcohol use disorder (RECLAIM) and started a trial in alcohol-associated liver disease (RESTORE), on the theory that a liver-directed mechanism could help conditions where the liver itself is the target of damage, not just a downstream beneficiary of weight loss.

The trade is that glucagon raises blood glucose. In a dual agonist the GLP-1 component is meant to offset that, and the trial data so far show glycemic control maintained, with minimal change in HbA1c in IMPACT and in the obesity trial. The what is glucagon page covers the hormone. Altimmune’s earliest human data, a Phase 1 single- and multiple-ascending-dose study in healthy overweight and obese volunteers (NCT04561245, completed 2021, n=100), established the safety and pharmacokinetics that later trials built on, though it did not publish a specific glucagon-to-GLP-1 potency ratio beyond the “balanced, roughly 1:1” description Altimmune has used since.

2. How well does pemvidutide work in MASH?

IMPACT, NCT05989711, randomised 212 adults with biopsy-confirmed MASH stage F2 or F3 fibrosis, screened from 1,557 patients at 83 sites in the US and Australia, to placebo (86), pemvidutide 1.2 mg (41), or 1.8 mg (85) weekly, dosed without titration. The 24-week biopsy results were published in The Lancet in November 2025 (PMID 41237796); 48-week topline data followed in December 2025 (Altimmune 48-week release) and were presented at EASL 2026, and the trial supported the FDA’s January 2026 Breakthrough Therapy Designation for pemvidutide in MASH. Altimmune had already secured Fast Track designation for pemvidutide in both MASH and, later, alcohol use disorder; Breakthrough Therapy is the stronger of the two designations and, unlike Fast Track, requires preliminary clinical evidence indicating the potential for substantial improvement over available therapy on a clinically significant endpoint. Neither designation changes the drug’s approval status: it remains investigational, and the FDA granted it based on the 24-week resolution data plus early improvements in liver fat and non-invasive fibrosis markers, not on a completed Phase 3 program.

The comparison readers want is with Wegovy, which won MASH approval on ESSENCE: steatohepatitis resolution in 62.9% versus 34.3% on placebo at 72 weeks, and fibrosis improvement in 36.8% versus 22.4%. Pemvidutide’s 24-week resolution rate is similar and its placebo rate lower, but the trials differ in length, size, and population, and no head-to-head exists. The what is MASH page explains the endpoints.

3. How much weight do people lose on pemvidutide?

Up to 15.6% at 48 weeks. MOMENTUM, NCT05295875, was the Phase 2 obesity trial in 391 adults with obesity or overweight and at least one comorbidity, no diabetes, randomised 1:1:1:1. Baseline was about 50 years old, BMI 37 kg/m², weight 104 kg, and 75% female; each arm held roughly 98 people. The 1.2 mg and 1.8 mg doses started immediately, with a short 4-week titration for the 2.4 mg arm.

In an MRI body-composition substudy of 67 MOMENTUM participants, 50 of them on pemvidutide, Altimmune reported a “lean loss ratio” of 21.9%, meaning lean mass made up about a fifth of the weight lost (EASD 2024 release); an earlier company analysis had put the figure at 25.5% (Altimmune, March 2024). Neither analysis has been published in a peer-reviewed journal, and lean mass measured this way is not the same as muscle. For scale, semaglutide 2.4 mg produced 14.9% at 68 weeks and tirzepatide 15 mg 20.9% at 72 weeks in their own trials. Altimmune has not started a Phase 3 obesity program; the company’s Phase 3 investment is in MASH, and its 2026 releases list MASH, alcohol use disorder and alcohol-associated liver disease as the indications in development (Altimmune Q2 2026 release).

4. What are the side effects of pemvidutide?

Gastrointestinal, mostly mild to moderate. Discontinuation numbers were low in the MASH trial, which used 1.2 and 1.8 mg, but higher in the obesity trial.

At 48 weeks, about 1% of pemvidutide participants had discontinued for adverse events, still favorable against placebo. Per-event rates for nausea and vomiting specifically are in the Lancet paper’s supplementary tables and have not been broken out in press materials. Glucagon agonism raises a specific question about heart rate and glucose; Altimmune reported no arrhythmias in IMPACT at 24 weeks, with glycemic control maintained and minimal change in HbA1c (IMPACT topline release), and no imbalance in cardiac adverse events versus placebo at 48 weeks. In the unrelated RECLAIM alcohol-use-disorder trial at the higher 2.4 mg dose, one serious adverse event, hyponatremia, occurred on pemvidutide and was judged possibly related by the investigator.

The obesity trial tells a different tolerability story. In MOMENTUM, which titrated only the 2.4 mg arm, gastrointestinal effects were higher at 1.8 and 2.4 mg than at 1.2 mg, though nausea was lower at 2.4 mg than at 1.8 mg (MOMENTUM 8-K release):

One drug-related serious adverse event, vomiting on 2.4 mg, was reported, with no major adverse cardiac events and similar rates of cardiac adverse events across arms. The Phase 3 trial uses a monthly titration to its 1.8 mg and 2.4 mg doses to improve tolerability.

5. What is the PERFORMA trial?

PERFORMA (NCT07795164) is the Phase 3, multicentre, multinational, two-cohort, randomised, double-blind, placebo-controlled MASH trial that began recruiting on July 30, 2026, following an end-of-Phase-2 meeting with the FDA that aligned on registrational parameters. It targets an estimated 1,800 participants: Cohort 1 enrolled by liver biopsy (F2 or F3 fibrosis) and Cohort 2 by non-invasive test criteria, in patients with noncirrhotic MASH. Altimmune says Cohort 1, about 990 patients, is designed to support accelerated approval on a 52-week biopsy endpoint of MASH resolution and/or fibrosis improvement, while Cohort 2, about 800 patients, adds safety data; doses are 1.8 mg and 2.4 mg after a one- or two-step monthly titration from 1.2 mg, and full approval would rest on liver-related events at about 60 months (PERFORMA release). Estimated primary completion (the primary endpoint data) is December 2028; estimated overall study completion is December 2032, and Altimmune expects the 52-week readout in 2029. Approval, if it comes, would follow the primary completion data at the earliest.

6. What did the RECLAIM alcohol use disorder trial show?

RECLAIM (NCT06987513) tested pemvidutide outside the liver and obesity space: 100 adults with obesity or overweight and moderate-to-severe alcohol use disorder, randomised 1:1 to pemvidutide 2.4 mg or placebo weekly for 24 weeks. Altimmune reported positive topline results on July 28, 2026.

The trial met its primary endpoint, and Altimmune plans to request an FDA end-of-Phase-2 meeting for the AUD program; the company frames the glucagon-driven liver effect as a possible point of differentiation from GLP-1-only drugs in a population prone to alcohol-related liver damage. Tolerability here was not as favorable as in the MASH trial: study-drug-related adverse events leading to discontinuation occurred in 5 of 50 participants (10%) on pemvidutide 2.4 mg, versus 0 of 50 (0%) on placebo, driven by 2 cases of vomiting, 1 constipation, 1 fatigue, and 1 exacerbation of hemorrhoids. A related 48-week Phase 2 trial in alcohol-associated liver disease, RESTORE (NCT07009860), finished enrolling about 120 patients in July 2026, with topline data expected in the second half of 2027 (Altimmune Q2 2026 release).

7. How does pemvidutide compare with the other liver-focused agonists?

The survodutide and efinopegdutide pages cover the other two glucagon dual agonists. For a log, an investigational drug is entered like any other: product, date, milligrams, and site. How GLP-1 tracking works covers what to record.

8. Pemvidutide FAQ

• What is pemvidutide used for?

  Nothing yet; it is investigational. Its lead indication is MASH, the liver disease formerly called NASH, where it resolved steatohepatitis in 58.5% of patients at 24 weeks. Altimmune also ran a Phase 2 obesity trial (MOMENTUM), where pemvidutide produced up to 15.6% weight loss at 48 weeks, and a Phase 2 trial in alcohol use disorder.

• How well does pemvidutide work in MASH?

  In IMPACT at 24 weeks (Lancet, PMID 41237796), MASH resolved without worsening of fibrosis in 58.5% (24/41) on 1.2 mg and 52.9% (45/85) on 1.8 mg versus 20.9% (18/86) on placebo, both p<0.0001. Fibrosis improvement without worsening of MASH was 33% and 36% versus 28%, not statistically significant at 24 weeks. By 48 weeks, a combined non-invasive fibrosis marker responded in 27.8% and 32.4% versus 3.2%.

• How much weight do people lose on pemvidutide?

  In MOMENTUM (n=391, randomized 1:1:1:1), 48 weeks in adults with obesity: 10.3% on 1.2 mg, 11.2% on 1.8 mg, and 15.6% on 2.4 mg versus 2.2% on placebo. In the MASH trial, 5.0% and 6.2% at 24 weeks and 7.5% on 1.8 mg at 48 weeks. Semaglutide 2.4 mg produced 14.9% at 68 weeks in STEP 1, in a separate trial.

• What are the side effects of pemvidutide?

  Gastrointestinal, mostly mild to moderate. In IMPACT, any adverse event occurred in 78% on 1.2 mg, 81% on 1.8 mg, and 67% on placebo. Discontinuation for adverse events was 0% on 1.2 mg and 1% on 1.8 mg versus 2% on placebo at 24 weeks, and about 1% of pemvidutide participants at 48 weeks. No treatment-related serious adverse events were reported in IMPACT. In the MOMENTUM obesity trial, which added a 2.4 mg arm in people without MASH, nausea affected 59.6% on 1.8 mg and 51.5% on 2.4 mg versus 11.3% on placebo, and 19.2% and 19.6% stopped for adverse events versus 6.2% on placebo. Tolerability was less favorable in the separate RECLAIM alcohol-use-disorder trial at the higher 2.4 mg dose: study-drug-related adverse events led to discontinuation in 5 of 50 participants (10%) on pemvidutide versus 0 of 50 (0%) on placebo, and one serious adverse event, hyponatremia, was reported on pemvidutide and judged possibly related.

• How is pemvidutide different from semaglutide?

  Semaglutide activates one receptor, GLP-1. Pemvidutide adds glucagon receptor agonism, which raises energy expenditure and acts directly on liver fat. Semaglutide is approved for MASH as Wegovy; pemvidutide is in Phase 3 for the same indication and no trial has compared them.

• Has pemvidutide received any FDA designations?

  Yes. The FDA granted Breakthrough Therapy Designation for pemvidutide in MASH in January 2026, based on the 24-week IMPACT data, after Altimmune had already obtained Fast Track designation for the program. Neither designation is an approval; both are meant to speed development and review.

• Has pemvidutide been studied for alcohol use disorder?

  Yes. RECLAIM (NCT06987513) randomized 100 adults with obesity or overweight and moderate-to-severe alcohol use disorder 1:1 to pemvidutide 2.4 mg or placebo for 24 weeks. Reported July 2026, it met its primary endpoint: heavy drinking days per week fell by 4.20 versus 2.75 on placebo (p=0.0014), and 64.4% of pemvidutide participants achieved a two-level reduction in WHO Risk Drinking Level versus 34.8% on placebo.

9. Sources