CagriSema (Cagrilintide + Semaglutide Combination)
CagriSema is a once-weekly injection combining cagrilintide (amylin analog) and semaglutide (GLP-1 agonist). In REDEFINE 1 (n=3,417), it produced 22.7% weight loss at 68 weeks, with 60% of patients losing 20%+ of body weight. Novo Nordisk filed the NDA in December 2025. FDA decision expected late 2026.
FormBlends Peptide Context
Reviewed May 14, 2026Use Cagrisema peptide guide as a decision-support page, not a shortcut. Its job is to frame benefits, dosing, evidence strength, sourcing, and safety boundaries in one place, especially where the search overlaps with peptide therapy. A useful reader should leave with better questions about clinician oversight, evidence quality, safety limits, cost, pharmacy path, and what changes for their own health history.
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Clinical decision snapshot
CagriSema authority snapshot
CagriSema is evaluated by mechanism, evidence quality, regulatory status, practical access, and safety questions a licensed clinician would need to review before use.
Evidence signal
Strong human evidence
Regulatory reality
Investigational, NDA under review
Safety screen
Nausea (55% vs 12.6% placebo in REDEFINE 1), Constipation (30.7% vs 11.6% placebo), Vomiting (26.1% vs 4.1% placebo) should be reviewed in context.
This page currently connects to 11 source-backed evidence items through visible references or structured citation data.
Decision path
What is the supervised-review path for CagriSema?
CagriSema should be evaluated by evidence quality, safety status, source quality, dosing context, and whether the goal fits a legitimate clinical pathway. This page is a research and decision aid, not a self-prescribing guide.
- Peptide
- CagriSema
- Category
- Weight Loss
- Evidence
- Strong human evidence
- FDA status
- Not FDA approved
Step 1
Check evidence level
CagriSema has strong Phase 3 evidence. REDEFINE 1 (n=3,417, NEJM 2025, PMID: 40544433) showed 22.7% weight loss at 68 weeks with 60% achieving 20%+ loss. REDEFINE 2 (n=1,206, NEJM 2025, PMID: 40544432) showed 13.7% weight loss and 73.5% A1C target achievement in T2D. REDEFINE 4 against tirzepatide 15 mg failed noninferiority (23.0% vs 25.5%). The pharmacological synergy between amylin and GLP-1 pathways is validated.
Review evidenceStep 2
Screen safety context
Nausea (55% vs 12.6% placebo in REDEFINE 1), Constipation (30.7% vs 11.6% placebo), Vomiting (26.1% vs 4.1% placebo) should be discussed in light of history, dose, and source.
Check side effectsStep 3
Confirm access route
If this is research-only or not directly offered, compare clinic and provider routes before taking action.
Compare clinicsLast updated: April 6, 2026
Typical Dosage
Once-weekly subcutaneous injection. 16-week titration: 0.25/0.25 mg (weeks 1-4), 0.5/0.5 (weeks 5-8), 1.0/1.0 (weeks 9-12), 1.7/1.7 (weeks 13-16), maintenance 2.4/2.4 mg (week 17+). Injection in abdomen, thigh, or upper arm.
Administration
Subcutaneous injection
Typical Cost
Not yet available. Projected $1,000-1,500/month at launch based on comparable pricing.
FDA Status
Not FDA Approved
Half-Life
Cagrilintide: 159-195 hours (~7-8 days). Semaglutide: ~165 hours (~7 days). Both support once-weekly dosing.
Onset of Action
Tmax 24-72 hours for both components. Steady state in approximately 4-5 weeks. Weight loss becomes clinically measurable within the first month.
Bioavailability
Semaglutide: ~89% subcutaneous. Cagrilintide: high subcutaneous (no published absolute value).
About CagriSema
CagriSema is a fixed-dose combination of two peptides administered as a single once-weekly subcutaneous injection. It pairs cagrilintide (a long-acting amylin and calcitonin receptor agonist, CAS: 1415456-99-3, MW: ~4,409 Da) with semaglutide (a GLP-1 receptor agonist, CAS: 910463-68-2, MW: ~4,114 Da). Developed by Novo Nordisk. The idea is simple: GLP-1 and amylin suppress appetite through different brain circuits. GLP-1 works through hypothalamic pathways. Amylin works through the area postrema in the brainstem. Because they're hitting different receptor populations in different regions, the appetite suppression adds up rather than plateauing. The REDEFINE 1 trial proved this out: cagrilintide alone produced 11.5% weight loss, semaglutide alone 14.9%, and the combination 22.7%. That's genuine pharmacological synergy, not just an additive effect. REDEFINE 1 (NEJM 2025, PMID: 40544433) enrolled 3,417 adults with overweight or obesity without T2D. At 68 weeks, the CagriSema group lost 22.7% of body weight (trial-product estimand) or 20.4% (efficacy estimand). 60% of patients lost 20% or more, and 23% lost 30% or more. Blood pressure dropped meaningfully versus placebo. REDEFINE 2 (NEJM 2025, PMID: 40544432) tested CagriSema in 1,206 adults with T2D. Weight loss was 13.7% versus 3.4% for placebo at 68 weeks. 73.5% of CagriSema patients achieved HbA1c at or below 6.5% versus 15.9% on placebo. The head-to-head against tirzepatide (REDEFINE 4) didn't go as well. CagriSema produced 23.0% weight loss versus 25.5% for tirzepatide 15 mg at 84 weeks. It failed to meet the noninferiority endpoint. This is a headwind for marketing positioning but doesn't block approval, since the trials versus placebo were strongly positive. Side effects are GI-heavy. Nausea hit 55% of CagriSema patients versus 12.6% on placebo in REDEFINE 1. Constipation was 30.7% versus 11.6%. Vomiting was 26.1% versus 4.1%. Most events were mild to moderate and concentrated during dose escalation. Discontinuation rates were 6% CagriSema versus 3.7% placebo. Novo Nordisk submitted the NDA on December 18, 2025. The FDA decision is expected late 2026. If approved, launch could happen late 2026 or early 2027. Pricing hasn't been announced but is projected at $1,000-1,500/month based on comparable products, though Novo Nordisk has signaled a willingness to compete on price (they cut Wegovy list price plans by up to 50% for 2027).
How CagriSema Works
CagriSema targets two separate appetite circuits through a single injection. Cagrilintide is a long-acting amylin and calcitonin receptor agonist that works through the area postrema (brainstem), promoting satiety, suppressing glucagon, and delaying gastric emptying. Semaglutide acts on GLP-1 receptors in the hypothalamus and nucleus tractus solitarius. Because the signals come from different receptor populations in different brain regions, the effects are additive rather than ceiling-limited. In REDEFINE 1, cagrilintide alone achieved 11.5% weight loss and semaglutide alone 14.9%, while the combination reached 22.7%.
Receptor targets:
Benefits
- 22.7% weight loss at 68 weeks in REDEFINE 1 (trial-product estimand)
- 60% of patients lost 20% or more of body weight
- 23% of patients lost 30% or more
- HbA1c below 6.5% in 73.5% of T2D patients (REDEFINE 2)
- Reduces both systolic and diastolic blood pressure versus placebo
- Single weekly injection (not two separate shots)
What Does the Research Say?
CagriSema has strong Phase 3 evidence. REDEFINE 1 (n=3,417, NEJM 2025, PMID: 40544433) showed 22.7% weight loss at 68 weeks with 60% achieving 20%+ loss. REDEFINE 2 (n=1,206, NEJM 2025, PMID: 40544432) showed 13.7% weight loss and 73.5% A1C target achievement in T2D. REDEFINE 4 against tirzepatide 15 mg failed noninferiority (23.0% vs 25.5%). The pharmacological synergy between amylin and GLP-1 pathways is validated.
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
New England Journal of Medicine, 2025 · DOI · PubMed
22.7% weight loss at 68 weeks (trial-product estimand); 60% achieved 20%+ weight loss; NDA-supporting trial
PubMed evidence trail
Research sources used to frame this page
For CagriSema, FormBlends checks the page topic against primary trials, systematic reviews, guidelines, and current PubMed-indexed literature where available. These citations are context, not medical advice, proof of eligibility, or a claim that every study applies to every patient.
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Primary STEP 1 trial source for semaglutide weight-management efficacy and adverse-event context.
PubMed
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance
Used for maintenance, discontinuation, and weight-regain discussions after semaglutide response.
PubMed
Tirzepatide Once Weekly for the Treatment of Obesity
Primary SURMOUNT-1 trial source for tirzepatide weight-loss ranges and tolerability.
PubMed
Continued Treatment With Tirzepatide for Maintenance of Weight Reduction
Used for continuation, stopping, and maintenance questions after initial weight loss.
PubMed
Potential Side Effects
- Nausea (55% vs 12.6% placebo in REDEFINE 1)
- Constipation (30.7% vs 11.6% placebo)
- Vomiting (26.1% vs 4.1% placebo)
- Diarrhea and abdominal pain
- GI events concentrated during dose escalation, mostly mild to moderate
- Discontinuation due to adverse events: 6% CagriSema vs 3.7% placebo
Drug Interactions
| Compound | Interaction | Severity |
|---|---|---|
| Insulin and sulfonylureas | Increased hypoglycemia risk from the semaglutide component. Dose adjustment needed. | major |
| Oral medications | Delayed gastric emptying from both components may alter absorption kinetics of co-administered oral drugs. | moderate |
| Other GLP-1 agonists | Do not combine with other GLP-1 or amylin receptor agonists. | major |
Who Is CagriSema For?
Women
Women represent ~73% of adverse reaction reports for semaglutide-class drugs. Postmenopausal women on HRT may have improved weight-loss response. Monitor for gallbladder events. Standard pregnancy contraindications apply.
Adults Over 50
Approximately 40% of weight lost may come from lean/muscle mass. High protein intake (100-120g/day) and resistance training 2-3x/week strongly recommended. Bone density monitoring advisable.
Athletes
GLP-1 agonists are not currently on WADA's prohibited list but are under monitoring. Delayed gastric emptying may impair fueling strategies during training.
Regulatory Status
FDA Approved
No
Compounding Legal
No
2026 HHS Status
Investigational, NDA under review
CagriSema is an investigational fixed-dose combination that has not been approved. Cagrilintide is not individually approved. Cannot be compounded or sold outside of clinical trials.
Last verified: 2026-04-06
Conditions Addressed
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