Efinopegdutide
Investigational GLP-1/glucagon dual receptor agonist being studied primarily for metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD), with weight-loss effects as well.
01 Overview
Efinopegdutide (MK-6024, formerly HM12525A/JNJ-64565111) is a once-weekly peptide dual agonist of the GLP-1 and glucagon receptors. Originally developed by Hanmi and later advanced by Merck, its glucagon component makes it attractive for reducing hepatic fat.
A Phase 2 trial reported superior liver-fat reduction versus the GLP-1 agonist semaglutide in patients with NAFLD, alongside weight loss. Its development has focused on liver disease. Human data are mid-stage and not yet supported by outcome trials.
02 Mechanism
Co-agonises GLP-1 and glucagon receptors; glucagon signalling increases hepatic fat oxidation and energy expenditure while GLP-1 suppresses appetite.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Trial dose | 5–10 mg/wk | SubQ | Doses studied in Phase 2 NAFLD trial |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced liver fatGreater relative liver-fat reduction in a head-to-head Phase 2 study. | Superior to semaglutide in NAFLD | Clinical | |
| Weight lossWeight reduction accompanying liver-fat improvement. | Moderate | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal effectsNausea, vomiting and diarrhoea common during titration. | Moderate | Very common | Clinical | |
| Heart-rate increaseModest heart-rate rise from glucagon component. | Mild | Common | Clinical |