Editorially reviewed · Last updated September 8, 2026 · How we review
Part of Weight Loss Drug Profiles: Every GLP-1 and GLP3 Agonist.
What Is CagriSema? Novo Nordisk's Amylin + GLP-1 Weight Loss Combination
Novo Nordisk filed a New Drug Application (NDA) for CagriSema with the FDA in December 2025, with a regulatory decision expected in 2026. If approved, CagriSema would be the first amylin + GLP-1 combination therapy on the market.
How CagriSema Works
The GLP-1 Pathway (Semaglutide)
Semaglutide is the same GLP-1 receptor agonist found in Wegovy and Ozempic. It mimics the incretin hormone GLP-1, which is released from the gut after meals. GLP-1 receptor activation reduces appetite through hypothalamic signaling, slows gastric emptying, and improves insulin secretion. Semaglutide 2.4 mg alone produces approximately 15-17% weight loss in clinical trials.
The Amylin Pathway (Cagrilintide)
Why Two Pathways Matter
GLP-1 and amylin receptors are entirely separate biological targets. They reduce food intake through different neural circuits in the brain. Activating both at the same time produces additive appetite suppression — which is exactly what the clinical data shows. In REDEFINE 1, the combination (20.4%) outperformed both semaglutide alone (14.9%) and cagrilintide alone (11.5%).
This dual-pathway strategy contrasts with retatrutide's approach. Retatrutide is a single molecule that activates three incretin-related receptors (GLP-1, GIP, and glucagon). CagriSema instead pairs an incretin agonist with a non-incretin amylin agonist — a fundamentally different pharmacological strategy.
Clinical Trial Data
REDEFINE 1 (Obesity Without Diabetes)
| Treatment | Weight Loss at 68 Weeks |
|---|---|
| CagriSema | -20.4% |
| Semaglutide 2.4 mg alone | -14.9% |
| Cagrilintide 2.4 mg alone | -11.5% |
| Placebo | -3.0% |
The trial also measured the proportion of participants reaching clinically meaningful weight loss thresholds:
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| Threshold | CagriSema | Semaglutide Alone | Cagrilintide Alone |
|---|---|---|---|
| Lost at least 20% | 53.6% | 26.5% | 15.4% |
| Lost at least 25% | 34.7% | 14.8% | 6.5% |
| Lost at least 30% | 19.3% | 8.7% | 1.6% |
Over half of CagriSema participants lost at least 20% of their body weight — nearly double the rate achieved by semaglutide alone.
REDEFINE 2 (Type 2 Diabetes)
REDEFINE 4 (Head-to-Head vs Tirzepatide)
REDEFINE 4 was an 84-week, open-label, head-to-head trial comparing CagriSema directly against tirzepatide 15 mg (the highest approved dose of Zepbound/Mounjaro).
| CagriSema | Tirzepatide 15 mg | |
|---|---|---|
| Weight loss (adherent participants) | -23.0% | -25.5% |
| Weight loss (all participants) | -20.2% | -23.6% |
| Non-inferiority met? | No — CagriSema failed non-inferiority | — |
Dosing
Side Effects
The most common side effects of CagriSema are gastrointestinal, consistent with both the GLP-1 and amylin drug classes. Data from REDEFINE 1:
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| Side Effect Category | CagriSema | Semaglutide Alone | Cagrilintide Alone | Placebo |
|---|---|---|---|---|
| Any GI event | 79.6% | 73.8% | 54.0% | 39.9% |
| Nausea | Most common | Most common | Most common | — |
| Constipation | Common | Common | Common | — |
| Diarrhea | Common | Common | Common | — |
| Vomiting | Common | Common | Less common | — |
Key points on tolerability:
GI events occurred more often with CagriSema than with either component. Nausea, diarrhea and vomiting peaked during escalation and decreased afterward; constipation remained relatively constant.
Serious adverse events were reported in 9.8% with CagriSema, 5.0% with semaglutide, 8.9% with cagrilintide and 6.1% with placebo. These are reported events, not a determination that treatment caused each event. Discontinuation due to adverse events occurred in 5.9%, 3.6%, 2.6% and 3.5%, respectively.
How CagriSema Compares to Other Weight Loss Drugs
REDEFINE 1 directly showed greater weight loss with CagriSema than with semaglutide 2.4 mg alone. REDEFINE 4 directly compared it with tirzepatide and did not meet its non-inferiority endpoint.
Those direct comparisons are more informative than a table ranking headline percentages from unrelated trials. There is no direct CagriSema–retatrutide comparison in the evidence summarized here.
CagriSema vs Retatrutide
CagriSema combines two medicines targeting amylin and GLP-1 pathways. Retatrutide is one molecule targeting GLP-1, GIP and glucagon.
FDA Timeline
CagriSema remains under regulatory review; approval and launch timing are not guaranteed:
- Phase 3 program (REDEFINE): Multiple trials completed, including REDEFINE 1, 2, and 4
- NDA filed: December 18, 2025
- FDA review: Currently under review
- Expected decision: 2026
- REDEFINE 4 setback: CagriSema failed to demonstrate non-inferiority to tirzepatide, a trial result that should be considered separately from the FDA’s independent benefit–risk review
If approved, CagriSema would be the first amylin + GLP-1 combination therapy available by prescription.
Frequently Asked Questions
What is CagriSema?
CagriSema is a fixed-dose combination of cagrilintide (an amylin receptor agonist) and semaglutide (a GLP-1 receptor agonist), delivered together in a single once-weekly subcutaneous injection. It is developed by Novo Nordisk and produced 20.4% weight loss at 68 weeks in the REDEFINE 1 Phase 3 trial.
How is CagriSema different from Wegovy?
Wegovy contains only semaglutide (a GLP-1 agonist). CagriSema contains semaglutide plus cagrilintide (an amylin agonist). The addition of cagrilintide provides a second appetite-reduction pathway, producing roughly 5-6 percentage points more weight loss than semaglutide alone (20.4% vs 14.9% in REDEFINE 1).
Is CagriSema better than tirzepatide?
In the head-to-head REDEFINE 4 trial, CagriSema achieved 23.0% weight loss vs tirzepatide's 25.5% at 84 weeks (in adherent participants). CagriSema failed to meet its primary endpoint of non-inferiority to tirzepatide. See CagriSema vs Tirzepatide for the full breakdown.
How does CagriSema compare to retatrutide?
They use different mechanisms, and there is no direct comparison in the trials summarized here. Separate headline percentages cannot establish superiority. See Retatrutide vs CagriSema.
What are the side effects of CagriSema?
The most common side effects are gastrointestinal: nausea, constipation, diarrhea, and vomiting. In REDEFINE 1, 79.6% of CagriSema participants experienced a GI event (vs 39.9% on placebo). Most were mild to moderate and occurred during the dose titration period.
When will CagriSema be available?
Novo Nordisk filed an NDA with the FDA in December 2025. A regulatory decision is expected in 2026. If approved, it would become available by prescription, though the exact launch timeline depends on the FDA review and any manufacturing ramp-up.
Is CagriSema FDA approved?
Not yet. CagriSema is under FDA review following an NDA filing in December 2025. A decision is expected in 2026.
What is amylin and why is it in CagriSema?
Amylin is a hormone co-secreted with insulin from pancreatic beta cells after meals. It reduces appetite by acting on brain regions involved in satiety, slows gastric emptying, and suppresses glucagon. Cagrilintide, the amylin component in CagriSema, provides appetite suppression through a pathway entirely separate from GLP-1 — making the combination additive.
How often do you take CagriSema?
REDEFINE trials studied weekly injections with protocol-controlled escalation toward a target of 2.4 mg cagrilintide plus 2.4 mg semaglutide. CagriSema remains investigational and has no approved prescribing schedule.
Sources
- Garvey WT, et al. "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity." New England Journal of Medicine. 2025;393:635-647. NEJM
- Novo Nordisk. "CagriSema demonstrated 23% weight loss in REDEFINE 4 trial." February 2026. Press Release
- Novo Nordisk. "CagriSema demonstrates superior weight loss in adults with obesity or overweight and type 2 diabetes in the REDEFINE 2 trial." March 2025. GlobeNewsWire
- Novo Nordisk. "Novo Nordisk files for FDA approval of CagriSema." December 2025. Press Release
- What this is
- Educational information, not medical advice. It reports published research — it doesn’t recommend that you use, obtain, or supply anything.
- Regulatory status
- Retatrutide and similar peptides are investigational — not approved by the FDA or any regulator. Semaglutide and tirzepatide are prescription-only medicines, available only through a licensed prescriber.
- Our standard
- Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
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Do not make decisions about your health without consulting a qualified healthcare provider. For trial enrolment, see ClinicalTrials.gov. More on how we review.
Sources
- REDEFINE 1 trial (NEJM)
New England Journal of Medicine
- CagriSema NDA filing
Novo Nordisk
NEJM
The Lancet
JAMA
FDA
ClinicalTrials.govRelated reading
What Is Cagrilintide? The Amylin Analog Behind CagriSema
An investigational amylin analog studied alone and with semaglutide in CagriSema; trial results and current development explained.
CagriSema vs Tirzepatide (Zepbound): REDEFINE 4 Head-to-Head Results
REDEFINE 4 reported 23.0% versus 25.5% weight loss under the efficacy estimand and did not meet its non-inferiority endpoint.
Retatrutide vs CagriSema (Cagrilintide + Semaglutide): Triple Agonist vs Amylin + GLP-1 Combo
Compare retatrutide with the cagrilintide–semaglutide combination, including REDEFINE 4 and why separate trial results do not establish superiority.
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