Mechanism of Action
Glucagon receptor activation adds thermogenesis (energy expenditure increase) and direct hepatic fat reduction beyond dual agonists (tirzepatide).
Clinical Use
Investigational — not approved. Phase III ongoing for obesity.
Contraindications
Same class warnings as GLP-1 agonists. Higher GI adverse event rates than dual agonists. Investigational only — not for clinical use.
Evidence Summary
Highest weight loss ever recorded in anti-obesity agent Phase II trial. Phase III currently enrolling. Only Phase II data available.
Key Studies
- 1.Jastreboff AM et al., NEJM 2023 — 24.2% weight loss at 48 weeks with 12mg dose. 100% achieved 5%+ loss. n=338, Phase II RCT
- 2.Network Meta-Analysis, PMC 2025 — superior efficacy: -16.34kg vs tirzepatide -11.82kg. n=12 RCTs included
Evidence Gaps
Phase III results PENDING. Only Phase II data (n=338). Higher adverse event rate vs comparators needs Phase III confirmation.
Emerging Research
If Phase III succeeds, likely most effective anti-obesity medication ever approved. NAFLD/MASH Phase II data expected.