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BARCELONA, Spain — Pemvidutide, an investigational dual glucagon/GLP-1 receptor agonist showed sustained improvements across liver, metabolic, and cardiovascular risk markers over 48 weeks in patients with metabolic dysfunction-associated steatohepatitis (MASH), according to new phase 2b data.

“In patients with MASH, where cardiovascular disease remains a leading cause of mortality, seeing this type of broad metabolic impact is highly relevant to overall patient outcomes,” said Mazen Noureddin, MD, professor of medicine at Houston Methodist in Houston, who presented the findings at the European Association for the Study of the Liver (EASL) Congress 2026.

These results build on growing interest in incretin-based therapies for MASH, particularly agents that may simultaneously target obesity, insulin resistance, hepatic inflammation, and fibrosis.

“MASH therapies that can address both liver disease and its underlying metabolic drivers are urgently needed to improve outcomes for patients,” said Noureddin.

Pemvidutide differs mechanistically from standard GLP-1 receptor agonists because it combines balanced glucagon and GLP-1 receptor agonism, with glucagon activity proposed to exert direct hepatic effects.

IMPACT Phase 2b Trial

The randomized, placebo-controlled IMPACT phase 2b trial enrolled 212 adults with biopsy-confirmed MASH and fibrosis stages F2 or F3. Participants were randomly assigned either to weekly subcutaneous pemvidutide at doses of 1.2 mg (n = 38) or 1.8 mg (n = 75) or to placebo (n = 68) for 48 weeks. No dose titration was used.

Baseline BMI ranged from approximately 38 to 39 across groups, and about 45% of participants had type 2 diabetes. The age of participants was from 52 to 55 years, 55%-61% were women, and liver fat content ranged from 19% to 20% across treatment groups.

The primary efficacy endpoints, measured at 24 weeks, were MASH resolution without worsening of fibrosis and/or fibrosis improvement without worsening of MASH. Secondary endpoints included noninvasive tests of fibrosis and weight loss measured at 24 and 48 weeks. 

The 24-week results, presented last year at The Liver Meeting 2025 and later published in The Lancet, showed that pemvidutide achieved statistically significant MASH resolution without worsening of fibrosis in up to 59.1% of participants.

The current 48-week analysis evaluated cardiometabolic risk factors, liver fat, fibrosis and inflammation markers, weight loss, and durability of effect beyond the original 24-week biopsy endpoint.

Cardiometabolic and Hepatic Parameters

At 48 weeks, the 1.8-mg weekly dose of pemvidutide produced significant improvements in multiple cardiometabolic parameters among patients with elevated baseline values. Triglycerides were reduced by 23.7%, total cholesterol by 15.4%, and low-density lipoprotein (LDL) cholesterol by 19.7%.

The 1.2-mg weekly dose also showed reductions across these lipid measures, with triglycerides reduced by 16.9%, total cholesterol by 15.5%, and LDL cholesterol by 16.5%. In the placebo group, the corresponding reductions were 3.3%, 5.1%, and 10.3%.

Patients receiving pemvidutide 1.8 mg also achieved mean weight loss of 7.5%, with weight reduction continuing throughout treatment and without evidence of plateauing at this dose (P < .0001 vs placebo). Waist circumference decreased by 5.3 cm, whereas systolic and diastolic blood pressure declined by 4.0 mm Hg and 2.2 mm Hg, respectively.

In addition, liver fat reductions from baseline reached 54.7% with the 1.8-mg dose vs 8.2% with placebo (P < .0001) at 48 weeks, similar to reductions seen at 24 weeks. The 1.2-mg dose showed a reduction in liver fat of 45.2% from baseline (P < .0001 vs placebo).

The trial also demonstrated improvements in noninvasive markers of fibrosis and hepatic inflammation. Mean change from baseline in Enhanced Liver Fibrosis (ELF) scores and liver stiffness measurements continued improving between weeks 24 and 48.

Approximately one third of patients receiving the 1.8-mg dose achieved both a ≥ 0.5 reduction in the ELF score and a ≥ 30% reduction in liver stiffness measurement compared with 3.2% of placebo-treated patients.

Alanine aminotransferase (ALT) also declined substantially for patients on pemvidutide. More than 70% of patients receiving active therapy achieved ALT normalization below 30 U/L at week 48 (P < .005), reported Noureddin.

The researchers also noted significant reductions in corrected T1, an MRI-based marker associated with hepatic fibroinflammatory activity. Reductions greater than 80 ms have previously been associated with histologic improvement in MASH.

“These findings suggest we are seeing broad and consistent effects across liver fat, fibrosis biomarkers, inflammation markers, weight, and cardiometabolic risk factors,” said Noureddin.

Safety Profile at 48 Weeks

The safety profile remained generally favorable through 48 weeks, and approximately 85% of pemvidutide-treated patients completed therapy compared with 77% receiving placebo.

Gastrointestinal adverse events were the most common side effects and were generally mild to moderate in severity, occurring predominantly during the first 8 weeks of treatment. Nausea occurred in 41.2% of patients receiving the 1.8-mg dose vs 17.4% in placebo; diarrhea in 22.4% vs 8.1% in placebo; and constipation in 17.6% in the 1.8-mg group and 12.2% in the 1.2-mg group compared with 11.6% in the placebo group.

Approximately 1% of patients discontinued treatment because of adverse events. No imbalance in cardiac adverse events was observed vs placebo.

Increasingly Competitive Treatment Landscape

Co-moderator Philip Newsome, MB ChB, professor of hepatology and director of the Roger Williams Institute of Liver Studies at King’s College London in London, England, remarked that the findings were encouraging and added to growing evidence that pemvidutide may be biologically effective in MASH.

“The positive signals are all moving in the same direction, which is very encouraging,” he said. However, he noted that the study included relatively modest patient numbers and that the intention-to-treat analysis provided a more realistic assessment of how the drug may perform in clinical practice.

He highlighted that the study reported preservation of muscle mass, which is an interesting finding, but “it remains unclear whether lean muscle mass itself or muscle function is the more important clinical outcome.” He added that larger studies will be needed to provide greater confidence in the results.

Also commenting was co-moderator Helena Cortez-Pinto, MD, PhD, professor of gastroenterology and hepatology at the Faculty of Medicine at the University of Lisbon in Lisbon, Portugal, who described the results as “very exciting.”

Pemvidutide is entering an increasingly competitive treatment landscape, she noted. “There are many drugs in development in this area, often with similar mechanisms of action, so we will probably end up with more than one therapeutic option available,” she said. “But these results are certainly very promising.”

The study investigators pointed out that pemvidutide’s combined glucagon/GLP-1 mechanism may offer differentiated metabolic and hepatic effects.

Dual agonists may have a better tolerability profile, said Cortez-Pinto, noting that they may be associated with fewer gastrointestinal adverse effects than GLP-1 receptor agonists alone, while still producing meaningful weight loss.

The multinational phase 3 PERFORMA trial will be launched later this year.

The study was funded by Altimmune. Noureddin reported having advisory, consulting, research, and speaker relationships with multiple pharmaceutical companies in this sector.Newsome reported having relationships with several pharmaceutical companies but not with Altimmune. Cortez-Pinto reported having no relevant conflicts related to pemvidutide or Altimmune.