Retatrutide vs CagriSema: the two next-generation obesity drugs, compared
Both target ~20%+ weight loss. One is a single-molecule triple agonist from Lilly; the other is a two-molecule amylin/GLP-1 combo from Novo Nordisk. The mechanisms and development paths diverge.
Retatrutide and CagriSema are the two most-watched investigational obesity drug candidates of 2025-2026. Both are pending or near-pending FDA submission. Both produce ~20%+ weight loss in Phase 3 data. They differ structurally: retatrutide is a single engineered peptide molecule that activates three receptors (GIP, GLP-1, glucagon); CagriSema is a fixed-dose combination of two molecules (cagrilintide + semaglutide) that hit amylin and GLP-1 receptors respectively.
| Field | Retatrutide | CagriSema (cagrilintide + semaglutide) |
|---|---|---|
| Brand names | LY-3437943 | |
| Manufacturer | Eli Lilly | Novo Nordisk |
| FDA approved | Investigational (Phase 3) | Submitted (pending approval) |
| Indication | Chronic weight management, T2D (pending) | Chronic weight management (pending) |
| Mechanism | Triple GIP / GLP-1 / glucagon receptor agonist (single molecule) | Amylin analog + GLP-1 agonist (two molecules, fixed-dose combination) |
| Delivery | Once-weekly subcutaneous injection | Once-weekly subcutaneous injection (combo pen) |
| Avg weight loss | ~24.2% at 48 weeks (Phase 2, 12 mg) | ~20.4% at 68 weeks (REDEFINE-1) |
Primary sources
- Retatrutide: Phase 2 retatrutide (NEJM, 2023)
- CagriSema (cagrilintide + semaglutide): REDEFINE-1 (NEJM, 2025)
Frequently asked
Which one will be approved first?
CagriSema is ahead regulatorily — Novo Nordisk has already submitted filings. Retatrutide is in Phase 3 with Lilly expected to file in 2026. If timing goes as expected, CagriSema approval in 2026-2027, retatrutide in 2027+.
Which produces more weight loss?
Retatrutide's Phase 2 (24.2% at 48 weeks) exceeds CagriSema's Phase 3 (20.4% at 68 weeks), but direct comparison is unfair without matched durations and head-to-head design. Both are at the top of the category.
Will either of them be more effective than tirzepatide?
Probably incrementally, but the real-world difference for any individual patient is impossible to predict from mean weight loss data alone. Response variability is high across all GLP-1-family drugs. Tolerability, cost, and access will often matter more than mean efficacy at the individual level.
Why do single-molecule vs combo approaches both work?
They hit different receptors in complementary patterns. Retatrutide's triple agonism adds glucagon-receptor effects to GIP/GLP-1; CagriSema adds amylin-receptor effects to GLP-1. Both escape the efficacy ceiling of GLP-1-only activation via mechanistic addition, through different routes.