CagriSema vs Retatrutide
Amylin Combo vs Triple Agonist — The Next-Gen Showdown (2026)
CagriSema (Novo Nordisk) and retatrutide (Eli Lilly) are the two most-watched next-generation obesity drugs. CagriSema pairs an amylin analog with semaglutide; retatrutide hits three receptors at once. Here's how the leading combo and the leading triple agonist compare.
CagriSema vs Retatrutide: At a Glance
- ✓Cagrilintide (amylin) + semaglutide (GLP-1)
- ✓Once-weekly subcutaneous injection
- ✓REDEFINE 1: ~22.7% weight loss (on-treatment)
- ✓NDA filed Dec 2025; FDA review in 2026
- ✓Closer to market of the two
- ✓Novo Nordisk
- ✓GLP-1 / GIP / glucagon triple agonist
- ✓Once-weekly subcutaneous injection
- ✓Highest reported weight loss of the class
- ✓TRIUMPH program: ~24–28.7% at 68 weeks
- ✓Still in Phase 3 (later to market)
- ✓Eli Lilly
Detailed Comparison
| Feature | CagriSema | Retatrutide |
|---|---|---|
| Mechanism | Amylin + GLP-1 | GLP-1 + GIP + glucagonBest |
| Receptors Targeted | Two pathways | Three receptors |
| Manufacturer | Novo Nordisk | Eli Lilly |
| Administration | Once-weekly injection | Once-weekly injection |
| Peak Weight Loss | ~22.7% (REDEFINE 1) | ~24–28.7% (TRIUMPH) |
| Stage | Filed; FDA review 2026 | Phase 3 ongoing |
| Time to Market | Sooner | Later |
| Extra Effects | Amylin satiety signaling | Glucagon energy expenditure |
How They Differ
Highest Ceiling
Retatrutide holds the highest reported weight-loss figures of any obesity drug in development — into the mid-to-high 20s percent.
Closer to Market
CagriSema is filed with the FDA (review in 2026), while retatrutide is still completing Phase 3 — so CagriSema is likely available first.
Different Biology
CagriSema adds amylin satiety signaling to GLP-1; retatrutide adds glucagon-driven energy expenditure plus GIP. Two distinct routes to fat loss.
Tolerability Unknowns
Triple agonism (retatrutide) and dual-pathway combos (CagriSema) both raise questions about GI side effects at high efficacy. Long-term data will tell.
Both Investigational
Neither is FDA-approved yet. Today's available options remain semaglutide and tirzepatide.
Two Pharma Giants
This is also Novo vs Lilly: CagriSema is Novo's next big bet; retatrutide is Lilly's. The race is shaping the future of obesity care.
Which Matters More?
On raw efficacy, retatrutide currently leads the entire obesity field — its triple-agonist mechanism (GLP-1 + GIP + glucagon) produced the highest reported weight-loss figures of any drug in development, in the mid-to-high 20s percent. CagriSema, combining an amylin analog with semaglutide, reached roughly 22.7% in REDEFINE 1 — outstanding, but a step below retatrutide's ceiling.
On timing, CagriSema leads: it's already filed with the FDA, while retatrutide is still finishing Phase 3. So the likely sequence is CagriSema first, retatrutide later. For a patient, "available sooner" can matter as much as "highest number."
Neither is on the market yet, so today's real choices remain semaglutide and tirzepatide. If you're tracking the pipeline, watch CagriSema's FDA decision and retatrutide's Phase 3 readouts. Keep your current protocol logged in Shotlee so you have a baseline when these arrive.
CagriSema vs Retatrutide: Frequently Asked Questions
Retatrutide currently holds the highest reported weight-loss figures (~24–28.7% in the TRIUMPH program) thanks to its triple-agonist mechanism. CagriSema reached roughly 22.7% in REDEFINE 1. Retatrutide has the higher ceiling; CagriSema is closer to market.
CagriSema combines cagrilintide (an amylin analog) with semaglutide (GLP-1) — two pathways. Retatrutide is a single molecule that activates three receptors (GLP-1, GIP, glucagon). Both are once-weekly injections.
CagriSema is likely first — Novo Nordisk filed its FDA application in December 2025, with review in 2026. Retatrutide is still in Phase 3, so it would come later.
No. Both are investigational. CagriSema is under FDA review; retatrutide is in Phase 3. Today's approved options remain semaglutide and tirzepatide.
Yes. Shotlee tracks any GLP-1-class protocol, including investigational combinations and triple agonists if you're in a trial — dose, weight, and side effects.
Track Any Next-Gen GLP-1 in Shotlee
Free dose logging, weight trends, and side-effect tracking for approved and investigational obesity drugs.