Pemvidutide Phase II

What It Is

Pemvidutide (development designation ALT-801) is a once-weekly subcutaneously injected synthetic peptide dual agonist at the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It is being developed by Altimmune Inc. (NASDAQ: ALT), a clinical-stage biopharmaceutical company based in Gaithersburg, Maryland. Pemvidutide is the lead asset in Altimmune's metabolic franchise and the principal clinical program driving the company's current commercial positioning.

Structurally, pemvidutide is based on a modified glucagon scaffold — a 29-amino-acid peptide whose sequence has been engineered for balanced affinity at both GLP-1R and GCGR, and for proteolytic stability. The molecule incorporates Altimmune's proprietary EuPort lipid conjugation technology — covalent attachment of a C-16 fatty acid (palmitoyl) to the peptide backbone that enables reversible non-covalent albumin binding in plasma, extending the plasma half-life to approximately 4 days and supporting once-weekly subcutaneous dosing. This fatty-acid-albumin-binding extended-half-life strategy is broadly analogous to the approach used in semaglutide (C-18) and tirzepatide, and follows the same pharmacological engineering principles first established with liraglutide.

The strategic rationale for GLP-1/glucagon dual agonism combines two complementary anti-obesity and hepato-metabolic mechanisms. The GLP-1R arm delivers the familiar appetite suppression, delayed gastric emptying, and insulinotropic effects that drive weight loss with semaglutide and tirzepatide. The GCGR arm — activation of the glucagon receptor, which is largely absent from pure GLP-1 agonists and GLP-1/GIP dual agonists — adds hepatic fatty acid oxidation, increased energy expenditure, and a thermogenic effect. This dual engagement is particularly well suited to treating both obesity and metabolic dysfunction-associated steatohepatitis (MASH, the renamed NASH) where hepatic lipid accumulation is the primary pathology. Pemvidutide competes in an active and crowded dual-agonist space with survodutide (Boehringer Ingelheim, BI 456906, GLP-1/GCGR), mazdutide (Innovent Biologics / Eli Lilly, IBI362, GLP-1/GCGR), cotadutide (AstraZeneca's earlier-generation GLP-1/GCGR, now advanced to retatrutide-class successors), and broader multi-agonist programs including retatrutide (Eli Lilly GLP-1/GIP/GCGR triple agonist).

Pemvidutide's Phase 2 clinical program has produced positive mid-stage data in both obesity (MOMENTUM trial) and MASH (IMPACT trial). Phase 3 in obesity has been prepared for advancement and the MASH regulatory pathway is being engaged with FDA. As of April 2026 the molecule is investigational only — not commercially available, not in compounded pharmacy supply, and not accessible outside the clinical trial framework.

Mechanism of Action

Pemvidutide's balanced dual-agonist mechanism layers two complementary metabolic effects.

• GLP-1 receptor agonism — central appetite suppression — Activation of GLP-1R in hypothalamic arcuate nucleus POMC neurons and brainstem area postrema drives satiety signaling, reduces food intake, and delays gastric emptying. This is the anorectic backbone shared with semaglutide, liraglutide, and tirzepatide.
• GLP-1 receptor agonism — islet insulinotropic effect — GLP-1R activation on pancreatic β-cells stimulates glucose-dependent insulin secretion. Pemvidutide therefore produces the same glycemic improvement as other GLP-1 agonists in type 2 diabetes populations.
• Glucagon receptor agonism — hepatic fatty acid oxidation — GCGR activation in hepatocytes upregulates mitochondrial β-oxidation pathways, increases fatty acid clearance from liver stores, and reduces hepatic steatosis. This is the mechanistic distinction from pure GLP-1 agonists and is the central rationale for the MASH indication.
• Glucagon receptor agonism — energy expenditure and thermogenesis — GCGR activation increases resting energy expenditure via thermogenic pathways in brown adipose tissue and possibly also skeletal muscle. This contributes additional weight loss beyond appetite suppression alone — the "weight loss without as much food restriction" theoretical advantage of dual agonism.
• Balanced receptor affinity — Altimmune emphasizes the ~1:1 GLP-1R : GCGR affinity ratio as a design feature. Too much GCGR activity produces problematic hyperglycemia; too little eliminates the dual-agonist advantage. Finding the balance has been the central engineering challenge for this class.
• EuPort C-16 lipid-albumin binding — The palmitoyl modification enables reversible non-covalent binding to plasma albumin, extending plasma half-life from hours to days and supporting once-weekly dosing. Analogous to the C-18 fatty acid attachment in semaglutide.
• Hepatic lipid clearance — MASH rationale — MASH is characterized by hepatic steatosis, inflammation, and progressive fibrosis. Glucagon receptor activation is uniquely positioned to drive hepatic lipid clearance — a mechanism that pure GLP-1 agonists (semaglutide) and GLP-1/GIP dual agonists (tirzepatide) engage only weakly and indirectly via weight loss.
• Potential anti-inflammatory signaling in liver — Preclinical data suggests dual agonism reduces hepatic inflammation markers beyond what weight loss alone achieves, supporting the MASH therapeutic positioning.
• Lean mass preservation (claimed) — Altimmune has emphasized data suggesting pemvidutide produces proportionally greater fat mass loss with less lean mass loss than pure GLP-1 agonists — a claim that, if confirmed in Phase 3, would meaningfully differentiate the class.
• Cardiovascular effects — GCGR activation produces modest heart rate elevation (~5–10 bpm), consistent with other GLP-1/GCGR dual agonists. Long-term cardiovascular outcomes will be characterized in Phase 3 and post-approval studies.

What the Research Shows

Pemvidutide's clinical evidence base consists of two principal Phase 2 trials — MOMENTUM in obesity and IMPACT in MASH — plus supporting Phase 1 pharmacokinetic and pharmacodynamic studies.

• MOMENTUM Phase 2 obesity trial — Randomized, double-blind, placebo-controlled, 48-week trial in adults with BMI ≥30 (or ≥27 with weight-related comorbidity) without diabetes. Pemvidutide at 1.2, 1.8, or 2.4 mg weekly SubQ vs placebo. Topline primary endpoint: 15.6% mean weight loss at 48 weeks at 2.4 mg dose (vs 2.2% placebo). Secondary endpoints favorable on waist circumference, blood pressure, lipids, and quality-of-life. Published in peer-reviewed journals and presented at major obesity and diabetes conferences 2024–2025.
• IMPACT Phase 2 MASH trial — Randomized, double-blind, placebo-controlled trial in biopsy-confirmed MASH patients. Pemvidutide vs placebo over 24 weeks. Primary endpoint: hepatic fat reduction assessed by MRI-PDFF. Topline: significant reduction in liver fat content (magnitude-of-effect reported in Altimmune disclosures; percentage reduction substantially greater than placebo). Secondary endpoints on liver enzymes, fibrosis markers, and biopsy histologic parameters.
• Lean mass preservation analyses — Altimmune has presented body-composition substudy data from MOMENTUM suggesting pemvidutide produces proportionally greater fat mass loss with less lean mass loss than published data on semaglutide and tirzepatide. If confirmed in Phase 3, this is a meaningful differentiation.
• Cardiovascular biomarker improvements — Reductions in blood pressure, triglycerides, LDL-C, and inflammatory markers — consistent with broader GLP-1 agonist class effects, possibly additively improved by GCGR-driven hepatic lipid clearance.
• Glycemic effects in non-diabetic obesity — As expected for a GLP-1 agonist in non-diabetic patients, modest glycemic improvements without meaningful hypoglycemia risk.
• Phase 1 pharmacokinetic characterization — Supports weekly SubQ dosing schedule; dose-proportional exposure; half-life approximately 4 days.
• Tolerability profile consistent with GLP-1 class — Nausea, vomiting, diarrhea dominating early-dose AE pattern; typically improves with dose titration. No novel safety signals in MOMENTUM as reported in Altimmune disclosures.
• Competitive positioning vs survodutide and mazdutide — Survodutide Phase 2 (Boehringer): ~18.7% weight loss at 46 weeks; Phase 2 MASH positive. Mazdutide Phase 2 (Innovent/Lilly): mid-teens percent weight loss in Chinese obesity population. Pemvidutide's ~15.6% at 48 weeks is competitive within the class but not category-leading on weight loss magnitude alone.
• Heart rate elevation — Consistent with GCGR class; modest resting heart rate increase observed. Longer-term cardiovascular outcomes await Phase 3.
• No Phase 3 data as of April 2026 — Phase 3 obesity trial is being prepared. Regulatory pathway for MASH is being discussed with FDA.

Human Data

Pemvidutide's human evidence base consists of investigational-drug clinical trial data only:

• Phase 1 single-ascending-dose (SAD) and multiple-ascending-dose (MAD) studies — Established pharmacokinetics, preliminary tolerability, and dose-range for Phase 2.
• Phase 1b 12-week proof-of-concept in obesity — Provided initial weight loss and metabolic signal supporting Phase 2 advancement.
• Phase 2 MOMENTUM obesity trial (NCT05295875) — 48-week randomized placebo-controlled trial across multiple dose arms. Primary endpoint of mean percent change in body weight at week 48. Reported topline ~15.6% weight loss at the 2.4 mg weekly dose.
• Phase 2 IMPACT MASH trial (NCT05908708) — 24-week randomized placebo-controlled trial in biopsy-confirmed MASH. MRI-PDFF primary endpoint; histologic secondary endpoints.
• Phase 2 HCV metabolic/liver study — Additional pemvidutide investigation in chronic hepatitis C-related metabolic / liver pathology.
• Clinical trial registry listings — Multiple ongoing and planned studies listed on ClinicalTrials.gov.
• Altimmune investor and scientific presentations — ADA 2024, EASL 2024, The Obesity Society 2024, AASLD 2024 — covering MOMENTUM and IMPACT interim/topline data.
• Peer-reviewed publication — MOMENTUM full results published in major metabolic/obesity journal.
• No commercial availability — Pemvidutide is not FDA-approved and not commercially accessible outside the clinical trial framework as of April 2026.
• No off-label compounded access — Because pemvidutide is an active IND-stage proprietary compound with no FDA approval, it is not eligible for 503A or 503B compounding in the United States.

Pemvidutide is a strictly investigational compound in active mid-stage development. It is not the same accessibility profile as commercially available semaglutide or tirzepatide; community use is not a relevant framing.

Dosing from the Literature

Pemvidutide dosing is defined by the Phase 2 clinical trial protocols. There is no off-label community dosing because the compound is not accessible outside clinical trials.

Reconstitution & Storage

Pemvidutide formulation and reconstitution procedures are proprietary to Altimmune and follow standard GLP-1-class once-weekly SubQ peptide presentation. Clinical-trial supply is typically provided as pre-filled pens or vial/syringe kits with standardized reconstitution and administration procedures.

• Clinical trial supply — Distributed by Altimmune's clinical operations and trial-site investigators only. No publicly detailed reconstitution protocol has been published outside the investigator brochure.
• Expected formulation — Aqueous subcutaneous injection formulation comparable to the semaglutide / tirzepatide class — buffered solution with preservative, ~1–3 mL per dose depending on strength.
• Route — SubQ abdomen, thigh, or upper arm; weekly rotation.
• Storage — Refrigerated 2–8°C; room-temperature stability parameters defined per product insert.
• Not available for off-label use — Because pemvidutide is not FDA-approved and not in compounded pharmacy supply, standard research-chemical and telehealth channels do not distribute this molecule as of April 2026.

→ For GLP-1 class dosing calculations, see the Kalios Dosing Calculator

Side Effects & Risks

Pemvidutide's AE profile from Phase 2 MOMENTUM and IMPACT follows the broadly anticipated GLP-1 and GLP-1/GCGR dual-agonist pattern:

• Nausea (most common) — Dominant early-titration AE, typically 30–40% incidence during the titration phase; improves over 4–8 weeks. Class effect.
• Vomiting — Less frequent than nausea; may require dose adjustment or discontinuation.
• Diarrhea — Common across GLP-1 class.
• Constipation — Can occur, particularly as gastric emptying slows.
• Decreased appetite — Intended effect but occasionally severe and treatment-limiting.
• Heart rate elevation — Modest resting HR increase (~5–10 bpm) characteristic of GCGR-containing dual agonists; larger than pure GLP-1 agonists. Cardiovascular significance being characterized in Phase 3.
• Hypoglycemia — Low risk as monotherapy in non-diabetic populations; higher risk when combined with insulin or sulfonylureas in diabetic populations.
• Injection site reactions — Mild, typically self-limiting.
• Acute pancreatitis — Class-label concern across GLP-1 agonists; discontinuation indicated if confirmed pancreatitis.
• Thyroid C-cell tumor / MTC risk — Class contraindication carried from rodent model findings across the GLP-1 agonist family. Contraindicated in personal or family history of medullary thyroid carcinoma or MEN2.
• Gallbladder disease — Increased rate of cholelithiasis in GLP-1 class; may apply here.
• Glucagon-specific considerations — GCGR activation can produce modest hepatic glucose output increase; balanced against GLP-1's insulinotropic effect in the dual-agonist design but still requires glycemic monitoring in T2D populations.
• Drug interactions — Delayed gastric emptying can reduce absorption of orally co-administered drugs; co-dosing separation may be required for narrow-therapeutic-index oral medications.
• Pregnancy / lactation — Not established; contraindicated.
• WADA status — As a weight-loss peptide not targeted at performance enhancement, not specifically named on the WADA Prohibited List as of 2026. Unlikely to become an anti-doping target.

Bloodwork & Monitoring

Pemvidutide monitoring in the clinical-trial context follows standard GLP-1 class practice plus enhanced hepatic monitoring for the MASH indication:

• Baseline CMP — Liver and kidney function pre-treatment; required before starting.
• HbA1c, fasting glucose — For glycemic tracking; particularly important in T2D populations and for any emergent glycemic concern.
• Lipid panel — Triglycerides, LDL-C, HDL-C baseline and periodic.
• Hepatic enzymes (AST, ALT, GGT) — Enhanced monitoring given MASH indication. Baseline, on-treatment at 12 and 24 weeks, then per protocol.
• Liver imaging (MRI-PDFF) — MASH-indication outcome measure; typically not standard clinical monitoring outside the research context.
• Fibrosis biomarkers (FIB-4, APRI, ELF) — Non-invasive liver fibrosis markers for MASH population; supportive rather than primary.
• Lipase, amylase — Baseline and if acute abdominal pain emerges. Pancreatitis class-effect surveillance.
• CBC — Standard baseline.
• TSH, calcitonin (if personal/family MTC/MEN2 history) — Calcitonin screening if concerned for MTC risk; generally not routine in patients without risk factors.
• Blood pressure, resting heart rate — Pre-dose and on-treatment periodic; heart rate increase is characteristic of GCGR-containing dual agonists.
• Body weight, waist circumference, body composition — Primary outcome tracking; DEXA or similar if body composition is part of the research protocol.

What to Expect — Timeline (from Phase 2 data)

The following summarizes typical trajectories observed in the MOMENTUM obesity Phase 2 dataset. Individual response varies.

• Week 1–4 (titration) — Dose titration period. GI tolerability effects (nausea, reduced appetite, occasional vomiting or diarrhea) dominate. Modest early weight loss (1–2%) commonly observed. Most tolerability issues peak here and improve over the following weeks.
• Week 4–12 — Weight loss accelerates as appetite suppression takes hold and GCGR-mediated energy expenditure contributes. Cumulative weight loss commonly reaches 5–8% by week 12 at the 2.4 mg target dose. Waist circumference reduction parallels weight loss.
• Week 12–24 — Continued steady weight loss trajectory. Lipid parameters improve (triglycerides, LDL-C). Blood pressure may decrease modestly. Resting heart rate plateaus at the ~5–10 bpm elevation characteristic of GCGR-containing dual agonists.
• Week 24–48 (primary endpoint window) — Peak weight loss approaches the ~15.6% mean reported at 48 weeks for the 2.4 mg dose. Metabolic markers (HbA1c, fasting glucose in pre-diabetic subpopulations) improve. MASH patients show reduced liver fat on MRI-PDFF.
• Responders vs non-responders — As with all GLP-1-containing therapies, response is bimodal. Strong responders (>10% weight loss at 48 weeks) are typical; non-responders (<5%) exist. Early 12-week response is often predictive of 48-week outcome.
• Maintenance phase — Whether weight loss is sustained with continued dosing, and what happens on discontinuation, is a Phase 3 question. Other GLP-1-class drugs (semaglutide, tirzepatide) show substantial weight regain on cessation; pemvidutide is likely to follow the class pattern.
• MASH-specific timeline — Liver fat reduction on MRI-PDFF emerges within 12–24 weeks; histologic improvements require longer follow-up and biopsy sub-studies.
• Practical tolerability — Most patients tolerate the 2.4 mg target dose; a subset require de-escalation due to GI effects. Stepped titration (every 4 weeks) reduces but does not eliminate GI burden.
• Body composition trajectory — Altimmune has emphasized proportionally greater fat mass loss relative to lean mass loss compared to published semaglutide / tirzepatide data. Phase 3 validation awaited.
• Return-to-baseline on discontinuation — Anticipated but not yet formally characterized. Chronic therapy is the expected use pattern if approved.

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Key References

1. Altimmune Inc. Pemvidutide (ALT-801) — Corporate Pipeline and Clinical Development Program Disclosures. 2023–2025. (Phase 2 MOMENTUM and IMPACT trial sponsor disclosures.)
2. ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Pemvidutide (ALT-801) in Adults Who Are Overweight or Obese (MOMENTUM). NCT05295875.
3. ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Pemvidutide (ALT-801) in Subjects With Non-Alcoholic Steatohepatitis (IMPACT). NCT05908708.
4. Ambery P, Parker VE, Stumvoll M, Posch MG, Heise T, Plum-Moerschel L, Tsai LF, Robertson D, Jain M, Petrone M, Rondinone C, Hirshberg B, Jermutus L. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018;391(10140):2607-2618. PMID: 29945727. (Foundational GLP-1/GCGR dual agonist class pharmacology — cotadutide / MEDI0382.)
5. Nahra R, Wang T, Gadde KM, Oscarsson J, Stumvoll M, Jermutus L, Hirshberg B, Ambery P. Effects of Cotadutide on Metabolic and Hepatic Parameters in Adults With Overweight or Obesity and Type 2 Diabetes. Diabetes Care. 2021;44(6):1433-1442. PMID: 33893157. (Cotadutide hepatic effects — foundational data for pemvidutide's MASH rationale.)
6. le Roux CW, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol. 2024;12(3):162-173. PMID: 38335975. (Survodutide competitor Phase 2.)
7. Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. PMID: 37366315. (Retatrutide competitor — triple agonist.)
8. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. PMID: 35658024. (Tirzepatide SURMOUNT-1 foundational obesity trial for class context.)
9. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. PMID: 33567185. (Semaglutide STEP 1 foundational obesity trial for class context.)
10. Harrison SA, Bedossa P, Guy CD, Schattenberg JM, Loomba R, Taub R, Labriola D, Moussa SE, Neff GW, Rinella ME, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509. PMID: 38324484. (First FDA-approved MASH drug — context for pemvidutide's MASH competitive landscape.)
11. Rinella ME, Noureddin M. STEPping Forward in the MASH Therapeutic Landscape. N Engl J Med. 2023. (MASH therapeutic landscape review.)
12. Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes Obes Metab. 2021;23(3):754-762. PMID: 33269530. (GLP-1 class appetite/gastric emptying mechanism context.)
13. Altimmune Inc. Q1–Q4 2024 and Q1 2025 earnings calls and investor presentations. Altimmune.com / SEC filings. (Phase 2 MOMENTUM and IMPACT interim and topline disclosures.)
14. Day JW, Ottaway N, Patterson JT, Gelfanov V, Smiley D, Gidda J, Findeisen H, Bruemmer D, Drucker DJ, Chaudhary N, Holland J, Hembree J, Abplanalp W, Grant E, Ruehl J, Wilson H, Kirchner H, Lockie SH, Hofmann S, Woods SC, Nogueiras R, Pfluger PT, Perez-Tilve D, DiMarchi R, Tschöp MH. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol. 2009;5(10):749-757. PMID: 19597507. (Foundational preclinical paper establishing GLP-1/glucagon dual agonism concept.)
15. Ambery P, et al. MEDI0382, a GLP-1/glucagon dual agonist, in type 2 diabetes: phase 2 efficacy and safety. Diabetologia. 2018;61(3):564-573. (Early GLP-1/GCGR class data.)