ALT-801
Evidence Grade D — Primarily preclinical. 12 published studies, mostly animal models. 7 registered clinical trials.
Pemvidutide is a once-weekly injection in Phase II/III development by Altimmune that activates both GLP-1 and glucagon receptors in a balanced 1:1 ratio. It requires no dose titration — patients start on the full dose from day one — which simplifies treatment. Body composition analysis showed 78% of weight lost was fat, with muscle better preserved than with many competing treatments.
12 published studies: 6 human, 0 animal, 0 in-vitro, 4 reviews
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose.
Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
Pemvidutide maintains balanced 1:1 activity at both GLP-1 and glucagon receptors, unlike other dual agonists that are biased toward GLP-1. The balanced profile maximises the contribution of glucagon receptor activation to energy expenditure and liver fat metabolism. A proprietary extended-release technology provides controlled delivery from the injection site.
In the Phase II MOMENTUM trial (391 patients), the highest dose achieved 15.6% weight loss at 48 weeks. A separate Phase IIb MASH trial (212 patients) showed liver disease resolution in up to 75% of patients at the highest dose — one of the strongest MASH results reported, earning FDA Breakthrough Therapy Designation. A discrepancy exists between higher discontinuation rates in the obesity trial (16-20% at higher doses) and excellent tolerability in the MASH trial (less than 1% discontinuation), which is not yet explained. The favourable body composition profile and no-titration dosing are practical differentiators. Phase III for MASH is planned for 2026. Pemvidutide faces intense competition from larger pharmaceutical companies pursuing the same dual indications.
RESTORE TRIAL: A Phase 2 Study Evaluating the Efficacy and Safety of Pemvidutide in the Treatment of Alcohol-Associated Liver Disease (ALD)
RECLAIM STUDY: A Phase 2 Evaluating the Efficacy and Safety of Pemvidutide in the Treatment of Alcohol Use Disorder (AUD) in Subjects With Obesity or Overweight
IMPACT TRIAL: Efficacy and Safety of Pemvidutide in Subjects With Nonalcoholic Steatohepatitis (NASH)
Extension of ALT-801 in Diabetic and Non-Diabetic Overweight and Obese Subjects With (NAFLD)
ALT-801 in Diabetic and Non-Diabetic Overweight and Obese Subjects With Non-alcoholic Fatty Liver Disease (NAFLD)
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Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for weight management (approved 2014). The LEADER trial, involving over 9,300 patients followed for nearly four years, established that liraglutide reduced the risk of major cardiovascular events by 13% — a landmark finding that helped establish GLP-1 treatments as a class with heart benefits. Saxenda is also approved for adolescents aged 12 and older. While historically significant, liraglutide has been substantially surpassed by newer agents. In a direct comparison, semaglutide achieved 15.8% weight loss compared to liraglutide's 6.4%. Liraglutide remains relevant as a lower-intensity option and as a benchmark against which newer treatments are measured. It has over a decade of real-world safety data, making it one of the best-understood medications in this class.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
HGH Fragment 176-191 has no marketing authorisation. A Phase IIa trial in obesity (approximately 300 patients) failed to demonstrate statistically significant weight loss at any dose tested. The clinical development programme was discontinued. The disconnect between animal data (which showed significant fat reduction in obese mice) and the failed human trial is the defining feature of this compound's development history. Products available through unregulated channels lack pharmaceutical quality assurance. The failed Phase II trial represents the highest level of clinical evidence available.
