CagriSema
InvestigationalA fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1 agonist) for chronic weight management. Phase 3 REDEFINE trials demonstrate 20-23% weight loss at 68 weeks. NDA submitted to FDA December 2025. First GLP-1/amylin combination therapy.
Cagrilintide-Semaglutide · NNC0174-0833
16 human studies
- Preclinical
- 11%
- Clinical
- 89%
Based on 18 cited sources
clinically demonstrated · high confidence
Demonstrated effect magnitude — not a recommendation or safety claim.
Research depth: two large adequately-powered phase 3 RCTs (REDEFINE-1 n=3,417; REDEFINE-2 n=1,206) plus phase 2 dose-finding, no published meta-analysis yet. Mechanism: GLP-1R and amylin/calcitonin receptor targets validated by cryo-EM binding plus functional agonism. Plausibility: full mechanism-to-weight-loss chain supported and coherent with incretin-class biology. Global coverage: 10-12 countries but predominantly one sponsor; NDA under review, not yet approved. Community experience: negligible niche discussion for an investigational agent. Effectiveness: clinical basis, ~20% weight loss (large effect, high confidence), tempered by REDEFINE-4 non-inferiority miss vs tirzepatide.
CagriSema combines two distinct appetite-suppressing peptide hormones into a single weekly injection, targeting complementary pathways in the brain.
How It Works (Simplified)
GLP-1 (semaglutide) and amylin (cagrilintide) activate separate “stop eating” pathways in the brain, creating a stronger combined appetite suppression effect.
Semaglutide targets the hypothalamus (hunger center) while cagrilintide additionally affects the hindbrain and septum (satiety and reward areas).
Clinical trials show the combination produces MORE weight loss than adding the two drugs together would predict, indicating true pharmacological synergy.
For people with prediabetes or diabetes, the combination improves blood sugar control more effectively than either component alone.
Key Research: Garvey WT et al. demonstrated in REDEFINE-1 that CagriSema produced 20.4% mean weight loss at 68 weeks versus 3.0% with placebo in adults with overweight or obesity. PMID:40544433
NDA Submission & REDEFINE Program (2025-2026)
NDA Filing: Novo Nordisk filed a New Drug Application for CagriSema in December 2025, based on the REDEFINE clinical program combining cagrilintide (amylin analog) with semaglutide.
REDEFINE 4 — Head-to-Head vs Tirzepatide: The REDEFINE 4 trial did not meet its primary endpoint of non-inferiority to tirzepatide, with CagriSema achieving 23% weight loss compared to 25.5% with tirzepatide at the highest dose. This result raised questions about CagriSema’s competitive positioning against established dual-agonist therapies.
Next Steps: Novo Nordisk has announced plans for a higher-dose CagriSema trial in H2 2026, aiming to improve upon the REDEFINE 4 results and strengthen the regulatory package.
Important Limitations
- FDA approval pending (NDA submitted December 2025)
- REDEFINE 4 failed non-inferiority vs tirzepatide (23% vs 25.5% weight loss)
- Long-term safety data beyond 68 weeks not yet available
- Cardiovascular outcomes trial (REDEFINE-3) still ongoing
- GI side effects occur in approximately 80% of patients (mostly mild-moderate, transient)
- Weight maintenance after discontinuation unknown
Dose titration phase. GI side effects (nausea, vomiting, diarrhea) most common during initiation. Appetite suppression typically begins within first 1-2 weeks.
PMID:40544433Continued dose escalation to maintenance dose. Weight loss acceleration observed. GI side effects typically diminish as tolerance develops.
PMID:40544433Maintenance phase with ongoing weight loss as participants progress toward the trial's 68-week endpoint.
PMID:40544433Continued weight loss with plateau approaching. Mean weight loss of 20.4% achieved at 68 weeks in REDEFINE-1. Cardiometabolic improvements sustained.
PMID:40544433Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Good Signs (6 indicators)
Warning Signs (5 indicators)
Bad Signs (6 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
BPC-157
CautionBoth affect GI function. BPC-157 is gastroprotective while semaglutide component slows gastric emptying. Monitor GI symptoms if combined.
Semaglutide
AvoidCagriSema already contains semaglutide. Combining with additional semaglutide would result in overdose. Do not use concurrently.
Tirzepatide
AvoidBoth are GLP-1 receptor agonists for weight management. Concurrent use would cause overlapping mechanisms and increased adverse effects.
Liraglutide
AvoidLiraglutide is a GLP-1 agonist. Combining with CagriSema would duplicate GLP-1 pathway activation and increase GI adverse effects.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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