Mechanism of Action
Dual glucagon (GCGR) and GLP-1 (GLP-1R) receptor agonism. GLP-1R: appetite suppression, insulin secretion. GCGR: increases energy expenditure, hepatic fat oxidation, thermogenesis. Synergistic effects on weight and liver fat.
Clinical Use
Investigational — not approved. Phase III SYNCHRONIZE program ongoing for obesity and MASH.
Contraindications
GI adverse events most common. Phase III safety profile still being characterized.
Evidence Summary
Phase II obesity: up to 18.7% weight loss at 46 weeks. Phase II MASH: improvement without worsening fibrosis (NEJM 2024).
Key Studies
- 1.Lancet Diabetes Endocrinol 2024 — dose-dependent weight loss up to 18.7% at 4.8mg at 46 weeks. ~5x greater than placebo. n=387, Phase II RCT
- 2.NEJM 2024 — MASH improvement without worsening fibrosis. Reduces liver fat, liver stiffness, and body weight. Phase II RCT
Evidence Gaps
No Phase III results yet. All efficacy data from Phase II with modest sample sizes.
Emerging Research
SYNCHRONIZE-1/2 Phase III ongoing. First GCG/GLP-1 CVOT (SYNCHRONIZE-CVOT) in 19 countries.