Pemvidutide

Origin and structure

Pemvidutide was designed at the small company Spitfire Pharma under the code SP-1373. Altimmune agreed to buy Spitfire in July 2019 and developed the compound as ALT-801, a code that Altor BioScience had earlier used for an unrelated cancer drug. The idea behind it goes back to oxyntomodulin, a gut hormone that activates both the GLP-1 and the glucagon receptor. Most drugs of this kind lean towards the GLP-1 receptor; pemvidutide was tuned to activate both about equally. In cell assays it was as potent at the glucagon receptor as at the GLP-1 receptor (EC50 values of 42 and 39 picomolar), whereas the developers put the balance of cotadutide and survodutide at about 5:1 and 7.5:1 in favour of GLP-1.

The peptide is a chain of 29 amino acids, amidated at the end. Its first 15 positions are those of human glucagon except position 2, where the unnatural amino acid Aib protects it against the enzyme DPP-4, and positions 18 to 23 copy a stretch of GLP-1. A lactam bridge between the side chains at positions 16 and 20 stabilises the chain. One lysine carries what Altimmune calls the EuPort domain: a C18 fatty acid joined to the peptide through a glucuronic acid sugar. This soap-like side chain binds albumin in the blood (more than 99%, by the developers' estimate) and forms micelles under the skin, so the drug enters the bloodstream slowly and lasts long enough for one injection a week. The molecular formula is C182H283N39O58, a mass of about 3.9 kDa.

How it is thought to work

Through the GLP-1 receptor pemvidutide acts like other GLP-1 drugs: it lowers appetite via the brain and raises insulin release when blood sugar is high. Through the glucagon receptor, which is plentiful in the liver, it is meant to act on the liver directly. Glucagon stimulates the burning of fatty acids there and inhibits the making of new fat, which the developers argue clears liver fat more effectively than weight loss alone. Glucagon also pushes blood sugar up, so the GLP-1 arm has to balance it. In the obesity trial, in people without diabetes, fasting glucose and HbA1c did not change, according to Altimmune.

Much of the case for the liver effect comes from animals. In mice with diet-induced MASH, 12 weeks of daily pemvidutide lowered body weight by about 25%, twice as much as semaglutide at the same molar dose, and reduced liver fat, liver enzymes and tissue markers of inflammation and fibrosis. In people, liver fat fell steeply within 12 weeks, by up to 68.5%, alongside a weight loss of at most 4.3%, which the developers read as a sign of a direct action on the liver. No human study has yet separated the glucagon effect from the effect of weight loss. GLP-1 receptors also play a part in the brain's reward pathways, which is the rationale for testing pemvidutide in alcohol use disorder.

Is pemvidutide approved?

No. As of October 2026 pemvidutide is not approved as a medicine anywhere.

In the EU no marketing-authorisation application has been filed, so it is not a registered medicine in the Netherlands. Altimmune reports that it received scientific advice from the EMA and the UK regulator MHRA on its phase 3 design. All pemvidutide trials so far have run in the US, Puerto Rico and Australia, none with sites in the Netherlands.

In the US the FDA granted Fast Track designation for MASH in 2023 and for alcohol use disorder in August 2025, and Breakthrough Therapy designation for MASH in January 2026, based on the 24-week IMPACT results. These designations can speed up development and review; they are not approvals. After an End-of-Phase 2 meeting with the FDA, announced in December 2025, Altimmune started the phase 3 trial PERFORMA in July 2026. It hopes to use the 52-week biopsy results, expected in 2029, for an accelerated approval.

Obesity has moved down the list. In 2024 Altimmune agreed a plan for four phase 3 obesity trials with the FDA, but by October 2026 none was registered, and the company now describes pemvidutide as being developed for MASH, alcohol use disorder and alcohol-associated liver disease.

Pemvidutide offered online as a research chemical is not the trial medicine. It has no marketing authorisation, is not made under a medicines licence and may not be used in people. Our shop does not sell pemvidutide.

What the research shows

Every trial with results so far has been phase 1 or 2, and all were sponsored by Altimmune. Only the liver trials have been published in journals; the obesity and alcohol results are company announcements that have not been peer reviewed. The main results:

• Phase 1b, fatty liver disease (J Hepatol 2025): 94 adults with overweight or obesity (BMI 28 or more) and at least 10% liver fat, 12 weeks; liver fat fell by 46.6%, 68.5% and 57.1% on 1.2, 1.8 and 2.4 mg, against 4.4% on placebo, and body weight by up to 4.3%. There were no severe or serious adverse events.
• Extension to 24 weeks (JHEP Reports 2025): 64 of those participants stayed on their dose; liver fat fell by 56.3%, 75.2% and 76.4% against 14.0%, liver fat returned to 5% or less in 53.8% on 1.8 mg, and weight fell by 5.1% to 6.2% against 1.4%.
• MOMENTUM, obesity (company results, November 2023): 391 adults with obesity or overweight and no diabetes, 48 weeks with diet and exercise; weight fell by 10.3%, 11.2% and 15.6% on 1.2, 1.8 and 2.4 mg against 2.2% on placebo, and was still falling on 2.4 mg when treatment ended. Among those assessed at week 48 on 2.4 mg, 51.8% had lost at least 15% and 32.1% at least 20%. Triglycerides fell by up to 34.9%, while LDL cholesterol did not change significantly.
• IMPACT, MASH (Lancet 2025): 212 adults with biopsy-confirmed MASH and fibrosis stage F2 or F3 at 83 sites in the US and Australia, started on their dose without escalation. At 24 weeks MASH had resolved without worsening of fibrosis in 58% on 1.2 mg and 52% on 1.8 mg against 20% on placebo. The second primary endpoint, fibrosis improving by at least one stage without worsening of MASH, was missed: 33% and 36% against 28%.
• IMPACT at 48 weeks (company results, December 2025; non-invasive tests only, as the registry lists no biopsy endpoint at 48 weeks): blood and imaging markers of fibrosis kept improving, and 27.8% and 32.4% had both a fall in ELF score of at least 0.5 and a fall in liver stiffness of at least 30%, against 3.2% on placebo. Liver fat fell by 45.2% and 54.7% against 8.2%, and weight by 4.5% and 7.5% against 0.2%.
• RECLAIM, alcohol use disorder (company results, July 2026): 100 adults with moderate to severe alcohol use disorder and a BMI of 25 or more, 2.4 mg or placebo for 24 weeks; heavy drinking days fell by 4.2 a week against 2.75 on placebo, and 64.4% against 34.8% dropped at least two WHO drinking-risk levels. Weight fell 9.1 percentage points more than on placebo.
• Still running: PERFORMA, a phase 3 trial of 1.8 or 2.4 mg against placebo in about 1,800 people with MASH and F2 to F3 fibrosis, with biopsy results at 52 weeks and liver outcomes over about five years; and RESTORE, a phase 2 trial in 121 people with alcohol-associated liver disease, with results expected in the second half of 2027.

Side effects and warnings

As with other GLP-1-based drugs, the side effects are mainly gastrointestinal and mostly mild to moderate. In MOMENTUM, nausea affected 25.5%, 59.6% and 51.5% on 1.2, 1.8 and 2.4 mg against 11.3% on placebo, and vomiting 6.1%, 27.3% and 27.8% against 3.1%. Side effects led 19.2% and 19.6% to stop on 1.8 and 2.4 mg, against 6.2% on placebo, mostly in the first 16 weeks. In IMPACT, adverse events of any kind were reported by 78% and 81% on 1.2 and 1.8 mg against 67% on placebo, but only 1 of 126 people on pemvidutide stopped because of them, against 2 of 86 on placebo. In RECLAIM, where 2.4 mg was reached in two steps, 44% had nausea against 24% on placebo and 10% stopped because of side effects related to the drug, against none.

GLP-1-based drugs usually raise heart rate a little. In MOMENTUM it rose by 3.1 and 2.5 beats per minute on 1.8 and 2.4 mg against a fall of 1.4 on placebo, with no excess of cardiac events or arrhythmias and no major cardiovascular events; in the 24-week fatty-liver trial heart rate did not change significantly. Serious side effects judged related to the drug were rare: one case of vomiting on 2.4 mg in MOMENTUM, and in RECLAIM one case of low blood sodium judged possibly related.

The evidence is short and comes entirely from trials paid for by the developer. The longest treatment lasted 48 weeks, the obesity and alcohol results have not been peer reviewed, and no trial has yet measured liver outcomes such as cirrhosis or cardiovascular events. Rare risks known from GLP-1 medicines, such as pancreatitis and gallbladder disease, cannot be judged from trials of this size.

Pemvidutide versus survodutide, mazdutide and approved MASH drugs

Pemvidutide, survodutide and mazdutide all combine GLP-1 and glucagon activity, but in different proportions: pemvidutide was built to be balanced, survodutide leans clearly towards the GLP-1 receptor. Their phase 2 biopsy results in MASH cannot simply be set side by side, because the trials measured different endpoints at different times: survodutide improved MASH in 43% to 62% after 48 weeks against 14% on placebo, while pemvidutide resolved MASH in 52% to 58% after 24 weeks against 20%. The two have never been compared directly. Survodutide is further along, with published phase 3 results in obesity, and mazdutide is approved in China.

For weight, the 15.6% after 48 weeks on 2.4 mg in MOMENTUM is in the range of semaglutide 2.4 mg, but it is a company figure from a phase 2 trial in which about a quarter of participants on pemvidutide did not finish, so it cannot fairly be set beside phase 3 results for semaglutide or tirzepatide. In the MASH trial the weight loss was smaller, 7.5% at 48 weeks on 1.8 mg.

Medicines for MASH already exist. In the EU resmetirom (Rezdiffra) has had a conditional marketing authorisation since 18 August 2025 for adults with MASH and F2 to F3 fibrosis, and in the US resmetirom (2024) and semaglutide (Wegovy, 2025) have accelerated approval for it. Altimmune's case for pemvidutide rests on a fast fall in liver fat and weight loss with few dropouts. Whether it also improves fibrosis and prevents cirrhosis is what PERFORMA has to show.

Frequently asked questions

Is pemvidutide approved?

No. As of October 2026 no regulator has approved it. No marketing application has been filed in the EU. In the US it has Breakthrough Therapy designation for MASH (January 2026) and Fast Track designations for MASH and alcohol use disorder, which speed up development but are not approvals. The phase 3 trial PERFORMA began in July 2026, with its first biopsy results expected in 2029.

How much weight did people lose on pemvidutide?

In the phase 2 obesity trial MOMENTUM, adults without diabetes lost 15.6% of their body weight after 48 weeks on 2.4 mg, against 2.2% on placebo, according to the company; those results have not been published in a journal. In the MASH trial IMPACT, weight loss was 7.5% after 48 weeks on 1.8 mg, against 0.2% on placebo.

Does pemvidutide work for fatty liver disease (MASH)?

Partly, on current evidence. In the phase 2b IMPACT trial, MASH resolved on biopsy in 52% to 58% of participants after 24 weeks, against 20% on placebo, and liver fat fell by up to 55% by week 48. Fibrosis, the scarring that drives cirrhosis, did not improve significantly on biopsy at 24 weeks, although blood and scan markers improved by 48 weeks. The phase 3 trial PERFORMA is testing fibrosis and liver outcomes directly.

How is pemvidutide different from Ozempic or Wegovy?

Ozempic and Wegovy contain semaglutide, which acts on the GLP-1 receptor only and is an approved medicine in the EU and the US. Pemvidutide also activates the glucagon receptor, about as strongly as the GLP-1 receptor, which is meant to act directly on liver fat. It is experimental: its phase 1 and 2 trials have enrolled about 1,100 people, placebo groups included, and it has never been compared head to head with semaglutide.

Is pemvidutide legal in the Netherlands?

It is not a registered medicine in the Netherlands or anywhere else, so no doctor can prescribe it and it may not be sold, advertised or supplied for use in people. So far no Dutch hospital has taken part in its trials. Pemvidutide offered online as a research chemical is not the trial medicine, and our shop does not sell it.

Is pemvidutide banned in sport?

Yes, at all times. It is not named on the WADA Prohibited List, but class S0 covers any pharmacological substance that the list does not otherwise address and that has no approval for human therapeutic use, including drugs still in clinical development. Approved GLP-1 medicines such as semaglutide are permitted; pemvidutide is not, because it is unapproved. In the Netherlands the Dopingautoriteit applies the same list.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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