Efocipegtrutide

Investigational (not approved by any regulator). FDA Fast Track for MASH; FDA and EMA orphan-drug designations for PBC, PSC, and IPF. No marketing application yet.

Efinopegdutide (MK-6024, formerly HM12525A and JNJ-64565111) is an investigational once-weekly subcutaneous dual agonist of the GLP-1 and glucagon receptors being developed by Merck for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and steatotic liver disease. It is a synthetic oxyntomodulin-based peptide - a modified GLP-1/glucagon dual-agonist sequence conjugated to a human IgG4 Fc fragment through a 10 kDa polyethylene glycol linker using Hanmi Pharmaceutical's LAPSCovery half-life-extension platform, which stretches dosing to once weekly. The design pairs the GLP-1 arm (appetite suppression, glycemic control, weight loss) with a glucagon arm that raises energy expenditure and acts directly on the liver to burn hepatic fat - the feature that sets it apart from pure GLP-1 drugs. In the head-to-head Phase 2a trial in NAFLD (Journal of Hepatology, 2023), efinopegdutide 10 mg cut liver fat content by 72.7% at 24 weeks versus 42.3% for semaglutide 1 mg, with two-thirds of efinopegdutide recipients falling below the 5% liver-fat threshold that defines a normal liver. Merck holds FDA Fast Track designation for the MASH program and is running Phase 2b studies plus a dedicated trial in compensated cirrhosis due to steatohepatitis; the earlier type 2 diabetes and obesity indications were discontinued in favor of the liver focus.

A once-weekly, long-acting GLP-1 receptor agonist from Hanmi Pharmaceutical built on a different molecular backbone than semaglutide or liraglutide: instead of a modified human GLP-1, efpeglenatide uses exendin-4 - the naturally DPP-4-resistant GLP-1 mimic first found in Gila monster venom - fused to a fragment of a human antibody (an IgG4 Fc) through a small polyethylene-glycol (mini-PEG) linker using Hanmi's LAPSCOVERY half-life-extension platform. That design lets one subcutaneous injection lower blood sugar, curb appetite and reduce body weight for a full week. Efpeglenatide is best known for the landmark AMPLITUDE-O cardiovascular outcomes trial (NEJM 2021), in which 4,076 people with type 2 diabetes and cardiovascular or kidney disease had a 27% lower rate of major adverse cardiovascular events (MACE hazard ratio 0.73) and a 32% lower rate of a composite kidney outcome (hazard ratio 0.68) versus placebo - the first cardiovascular outcomes win for an exendin-based GLP-1 and one of the clearest kidney signals in the class, with benefit seen regardless of whether patients were also taking an SGLT2 inhibitor. Originally licensed to Sanofi and then returned to Hanmi in 2020, efpeglenatide is now being advanced primarily for obesity and overweight, with a Phase 3 program that has completed enrollment and a targeted first launch in South Korea in the second half of 2026. It is an investigational (not yet approved) prescription medicine, not a supplement or research chemical.

Efruxifermin (development codes EFX, AKR-001; originally AMG 876) is an investigational, once-weekly, subcutaneously injected analog of the metabolic hormone fibroblast growth factor 21 (FGF21) being developed by Akero Therapeutics for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), including both pre-cirrhotic fibrosis and compensated (F4) cirrhosis. It is a bivalent Fc-FGF21 fusion protein - two engineered FGF21 sequences fused to a human immunoglobulin (IgG1) Fc domain - a design distinct from the glycoPEGylation used by its main FGF21-class rival, pegozafermin. The Fc fusion extends the very short half-life of native FGF21 to support once-weekly dosing while preserving agonism at FGF receptors (FGFR1c/2c/3c) together with the co-receptor beta-Klotho. In the 96-week Phase 2b HARMONY trial in biopsy-confirmed F2-F3 MASH, at least a one-stage improvement in fibrosis without worsening of MASH was reached by about 75% of patients on 50 mg and 46% on 28 mg versus 24% on placebo (published in The Lancet, August 2025). In the Phase 2b SYMMETRY trial in compensated MASH cirrhosis, about 39% of 50 mg patients with paired week-96 biopsies achieved reversal of cirrhosis without worsening of MASH versus 15% on placebo (published in the New England Journal of Medicine). Efruxifermin holds FDA Breakthrough Therapy designation and has advanced into the Phase 3 SYNCHRONY program (SYNCHRONY Histology in F2-F3 MASH, SYNCHRONY Outcomes in F4 compensated cirrhosis, and SYNCHRONY Real-World in non-invasively diagnosed MASH/MASLD, whose double-blind portion completed enrollment with safety results expected in 2026).

The first dual GCG/GLP-1 receptor agonist approved in China for obesity and T2D, with Phase 3 showing up to 20.1% weight loss at the 9 mg dose and superiority over semaglutide.

Pegozafermin (development code BIO89-100) is an investigational, long-acting analog of fibroblast growth factor 21 (FGF21) being developed for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and for severe hypertriglyceridemia (SHTG). Originally developed by 89bio and acquired by Roche in a deal announced in September 2025 (about $2.4 billion upfront and up to roughly $3.5 billion including a contingent value right), it uses site-specific glycoPEGylation to extend the very short half-life of native FGF21 to roughly 55-100 hours, enabling once-weekly or once-every-two-weeks subcutaneous dosing. FGF21 is a metabolic hormone that acts on liver, fat, and other tissues to improve insulin sensitivity, lower triglycerides, and exert direct anti-fibrotic and anti-inflammatory effects. In the Phase 2b ENLIVEN trial in biopsy-confirmed F2-F3 MASH, the 44 mg every-two-weeks dose produced at least a one-stage fibrosis improvement without worsening of MASH in about 27% of patients versus 7% on placebo, and MASH resolution without worsening of fibrosis in about 26% versus 2% on placebo, with benefits sustained through week 48. Pegozafermin holds FDA Breakthrough Therapy designation and EMA PRIME status for MASH and has advanced into the Phase 3 ENLIGHTEN program (ENLIGHTEN-Fibrosis in non-cirrhotic F2-F3 MASH and ENLIGHTEN-Cirrhosis in compensated F4 cirrhosis), plus the Phase 3 ENTRUST trial in SHTG.

A GLP-1/glucagon dual receptor agonist with FDA Breakthrough Therapy Designation for MASH, showing strong weight loss and liver benefits in Phase 2 trials.

An investigational triple agonist (GIP/GLP-1/glucagon) studied for obesity and metabolic disease.

A dual GLP-1/glucagon receptor agonist with FDA Breakthrough Therapy designation for MASH and Priority Review NDA filed February 2026. Phase 3 SYNCHRONIZE-1 reported 16.6% weight loss at 76 weeks; approval possible Q3 2026.

A dual GIP/GLP-1 receptor agonist FDA-approved for type 2 diabetes, weight management, and MASH with liver fibrosis.