Cagrilintide is a long-acting amylin analogue developed by Novo Nordisk that works through a different pathway than GLP-1 drugs like Ozempic. When combined with semaglutide as CagriSema, the pair produced 22.7% mean body weight loss at 68 weeks in the REDEFINE 1 trial. That combination is the first drug to target both amylin and GLP-1 receptors simultaneously.
Cagrilintide monotherapy produced 11.8% weight loss at 68 weeks in a dedicated Phase 3 trial. The real value remains the combination. CagriSema attacks obesity through two independent appetite pathways: amylin suppresses hunger through the hypothalamus while semaglutide slows gastric emptying and reduces food noise through GLP-1 receptors.
| Quick Reference | Details |
|---|---|
| Drug | Cagrilintide (AM833/NN9838) |
| Developer | Novo Nordisk |
| Type | Long-acting amylin receptor agonist |
| Combination product | CagriSema (cagrilintide + semaglutide) |
| Half-life | 159-195 hours (6.6-8.1 days); tmax 24-72 hours |
| Mechanism | Dual amylin + calcitonin receptor agonist |
| CagriSema weight loss | 22.7% at 68 weeks (REDEFINE 1) |
| Cagrilintide alone | 11.8% at 68 weeks (Phase 3) |
| NDA filed | December 18, 2025 |
| FDA approved? | No (NDA filed Dec 2025, decision expected 2026-2027) |
| Maintenance dose | 2.4 mg/week |
| GI adverse events | 79.6% (mostly mild and transient) |
This article covers what cagrilintide is, how the amylin pathway works, CagriSema clinical trial data, dosage titration schedules, and comparisons to existing weight loss drugs.
This is educational content. Consult a healthcare provider before starting any medication.
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What Is Cagrilintide?
Cagrilintide (developmental codes AM833/NN9838) is a synthetic version of amylin, a hormone your body produces alongside insulin from the beta cells of the pancreas. Natural amylin is released every time you eat. It signals fullness to your brain, slows digestion, and suppresses glucagon, which lowers blood sugar.
Natural amylin has a half-life of about 13 minutes. Cagrilintide is engineered with a half-life of 159 to 195 hours (6.6 to 8.1 days), with peak plasma concentration (tmax) reached between 24 and 72 hours after injection (PMID 33894838). This pharmacokinetic profile allows once-weekly subcutaneous dosing. Cagrilintide activates both the amylin receptor (AMY1R/AMY3R) and the calcitonin receptor (CTR), which is why it is classified as a dual amylin and calcitonin receptor agonist.
The critical distinction from GLP-1 drugs: cagrilintide works through a different brain pathway. Semaglutide and tirzepatide suppress appetite primarily through GLP-1 receptors in the gut and brainstem. Cagrilintide acts on the hypothalamus through amylin receptors, affecting both homeostatic hunger (your body's energy balance system) and hedonic hunger (the reward-driven desire to eat). This dual-pathway action is why the combination outperforms either drug alone.
How Cagrilintide Works
When cagrilintide binds to AMY1R and AMY3R receptors in the area postrema and hypothalamus, three things happen. These receptor subtypes are formed when calcitonin receptors associate with receptor activity-modifying proteins RAMP1 and RAMP3, which modulate receptor sensitivity and signaling (PMID 40609154).
- 1.Appetite suppression through satiety centers. The hypothalamus receives stronger "full" signals after eating, reducing both how much you eat and how often you think about food. Amylin receptors in the area postrema and nucleus tractus solitarius mediate this effect (PMID 36883831).
- 2.Slowed gastric emptying. Food moves through your stomach more slowly, extending the feeling of fullness after meals. This overlaps with GLP-1's mechanism but acts through a separate receptor pathway.
- 3.Glucagon suppression. By reducing postprandial glucagon release, cagrilintide helps prevent blood sugar spikes after meals. This is particularly relevant for patients with type 2 diabetes.
The hedonic hunger component is notable. Most GLP-1 drugs primarily reduce homeostatic hunger (the physical sensation). Cagrilintide also targets the reward pathways that drive cravings for specific foods, particularly high-calorie options. Early research suggests this may explain why CagriSema patients report less food obsession than patients on GLP-1 drugs alone.
Dosage Titration Schedule
The standard cagrilintide titration follows the Phase 3 REDEFINE trial protocol. Dose escalation occurs every 4 weeks to minimize gastrointestinal side effects.
| Week | Cagrilintide Dose | Administration |
|---|---|---|
| 1-4 | 0.25 mg | Once weekly, subcutaneous |
| 5-8 | 0.5 mg | Once weekly, subcutaneous |
| 9-12 | 1.0 mg | Once weekly, subcutaneous |
| 13-16 | 1.7 mg | Once weekly, subcutaneous |
| 17+ | 2.4 mg (maintenance) | Once weekly, subcutaneous |
An alternative rapid titration schedule used in some trials starts at 0.6 mg and escalates every 2 weeks to reach a 4.5 mg maintenance dose.
When used as CagriSema, the semaglutide component follows its own titration schedule simultaneously. The semaglutide dose in CagriSema reaches 2.4 mg (the same as Wegovy's maintenance dose). Both components are administered as separate injections on the same day.
For context on semaglutide dosing, see our semaglutide dosage chart. For reconstitution guidance, see our semaglutide mixing guide.
Clinical Trial Results
Novo Nordisk has tested cagrilintide through multiple clinical programs, including the Phase 2 dose-finding study, the CagriSema REDEFINE programme, and a dedicated cagrilintide monotherapy Phase 3 trial.
Phase 2 Dose-Finding Study
The Phase 2 trial enrolled 706 participants across 57 sites in 10 countries, with results published in The Lancet in 2021 (PMID 34798060). Five cagrilintide doses were tested: 0.3, 0.6, 1.2, 2.4, and 4.5 mg weekly.
| Dose | Weight Loss (%) | Weight Loss (kg) |
|---|---|---|
| 0.3 mg | 6.0% | 6.4 kg |
| 0.6 mg | 6.8% | 7.2 kg |
| 1.2 mg | 9.1% | 9.7 kg |
| 2.4 mg | 9.4% | 10.0 kg |
| 4.5 mg | 10.8% | 11.5 kg |
| Placebo | 3.0% | 3.2 kg |
| Liraglutide 3.0 mg | 9.0% | 9.6 kg |
At the highest dose, cagrilintide 4.5 mg outperformed liraglutide 3.0 mg: 10.8% versus 9.0% weight loss at 26 weeks. Gastrointestinal adverse events ranged from 41% to 63% across cagrilintide doses compared to 32% for placebo. This trial established 2.4 mg as the optimal balance of efficacy and tolerability for Phase 3 development.
REDEFINE 1: CagriSema in Obesity
The headline trial enrolled 3,417 adults with obesity (BMI 30+) or overweight with comorbidities (BMI 27+) without type 2 diabetes. Participants received CagriSema or placebo for 68 weeks.
| Metric | CagriSema | Placebo |
|---|---|---|
| Mean weight loss | 22.7% | 3.0% |
| Achieved 20%+ loss | 60% | Not reported |
| Achieved 30%+ loss | 23% | Not reported |
| Reached BMI below 30 | 50.7% | 10.2% |
| GI adverse events | 79.6% | Lower |
The 22.7% result is competitive with tirzepatide's 22.5% from SURMOUNT-1. The mechanism is entirely different (amylin + GLP-1 versus GLP-1 + GIP), but the weight loss magnitude is comparable.
The 79.6% GI adverse event rate is high, but trials classified most events as mild and transient. Nausea peaks during dose escalation and resolves at stable doses, the same pattern seen with semaglutide and tirzepatide.
REDEFINE 2: CagriSema in Type 2 Diabetes
REDEFINE 2 enrolled 1,206 participants (904 CagriSema, 302 placebo) with type 2 diabetes and obesity, with results published in the New England Journal of Medicine (PMID 40544432).
| Metric | CagriSema | Placebo |
|---|---|---|
| Mean weight loss | 13.7% | 3.4% |
| HbA1c at or below 6.5% | 73.5% | 15.9% |
| GI adverse events | 72.5% | 34.4% |
CagriSema produced 13.7% weight loss at 68 weeks versus 3.4% for placebo. This is lower than the 22.7% seen in REDEFINE 1, consistent with the established pattern that patients with type 2 diabetes lose less weight on anti-obesity drugs. The glycemic benefit was substantial: 73.5% of CagriSema patients reached HbA1c at or below 6.5%, compared to 15.9% on placebo.
REDEFINE 4: CagriSema vs. Tirzepatide (Head-to-Head)
REDEFINE 4 was an open-label, head-to-head trial comparing CagriSema directly against tirzepatide 15 mg in 809 adults with BMI 30 or higher (mean baseline weight 114.2 kg). Results were reported by Novo Nordisk in February 2026 (GlobeNewswire, Feb 23, 2026).
| Metric | CagriSema | Tirzepatide 15 mg |
|---|---|---|
| Weight loss (efficacy estimand) | 23.0% | 25.5% |
| Weight loss (treatment regimen estimand) | 20.2% | 23.6% |
The primary endpoint was noninferiority of CagriSema to tirzepatide, and this endpoint was not met. Tirzepatide produced numerically greater weight loss by both estimands. The open-label design is an important methodological caveat: participants knew which drug they received, which can influence adherence and reporting.
These results place CagriSema and tirzepatide in a similar efficacy range, though tirzepatide holds a modest advantage. The drugs work through entirely different mechanisms (amylin + GLP-1 versus GLP-1 + GIP), which preserves CagriSema's clinical value as an alternative for non-responders to GIP-based therapy.
Cagrilintide Monotherapy Phase 3
A dedicated Phase 3 trial tested cagrilintide as a standalone drug, separate from the CagriSema combination. Results were reported in September 2025 (GlobeNewswire, Sep 16, 2025).
| Metric | Cagrilintide | Placebo |
|---|---|---|
| Mean weight loss | 11.8% (12.5 kg) | 2.3% (2.5 kg) |
| Achieved 15%+ loss | 31.6% | 4.7% |
| Discontinuation due to nausea | 1.0% | Not reported |
Cagrilintide alone produced 11.8% weight loss at 68 weeks, confirming that the amylin pathway drives meaningful weight reduction independently of GLP-1. The tolerability profile was favorable: only 1.0% of participants discontinued due to nausea, lower than rates typically seen with GLP-1 agonists.
Based on these results, Novo Nordisk launched the RENEW dedicated Phase 3 programme in Q4 2025 to pursue regulatory approval for standalone cagrilintide.
The 25% Target Miss
Novo Nordisk had publicly targeted 25% mean weight loss for CagriSema. The actual result of 22.7% missed this target. When the results were announced, Novo Nordisk's stock dropped approximately 15%.
Context matters here. The 22.7% figure matches tirzepatide's efficacy from cross-trial comparison, though the head-to-head REDEFINE 4 trial later showed tirzepatide at 25.5% versus CagriSema at 23.0%. The market reaction was driven by expectations, not by poor results. CagriSema is still among the most effective obesity drugs ever tested.
For comparison: semaglutide alone produces about 15% weight loss. Tirzepatide produces 22.5-25.5% depending on the trial. Retatrutide (triple agonist, still investigational) produces about 28.7%.
CagriSema vs. Other Weight Loss Drugs
| Drug | Mechanism | Max Weight Loss | FDA Status | Developer |
|---|---|---|---|---|
| Semaglutide (Wegovy) | GLP-1 | ~15% | Approved | Novo Nordisk |
| Tirzepatide (Zepbound) | GLP-1 + GIP | ~22.5-25.5% | Approved | Eli Lilly |
| CagriSema | GLP-1 + Amylin | ~22.7% | NDA filed | Novo Nordisk |
| Cagrilintide (mono) | Amylin | ~11.8% | Phase 3 | Novo Nordisk |
| Retatrutide | GLP-1 + GIP + Glucagon | ~28.7% | Phase 3 | Eli Lilly |
| Survodutide | GLP-1 + Glucagon | ~19% | Phase 3 | Boehringer |
The head-to-head REDEFINE 4 trial showed tirzepatide 15 mg at 25.5% versus CagriSema at 23.0%, with tirzepatide holding a modest advantage. A network meta-analysis (PMC11642503) found that CagriSema produces 9.07% additional weight loss compared to semaglutide alone, confirming that adding the amylin pathway to GLP-1 delivers meaningful incremental benefit.
CagriSema's competitive position is nuanced. It uses a fundamentally different mechanism from tirzepatide. This matters because patients who do not respond well to GLP-1 + GIP (tirzepatide's mechanism) may respond to GLP-1 + amylin (CagriSema's mechanism). Having drugs with different mechanisms gives physicians more options.
Cagrilintide monotherapy shows significantly lower vomiting rates than semaglutide or liraglutide, with only 1.0% discontinuing due to nausea. This tolerability advantage may make standalone cagrilintide attractive for patients who cannot tolerate GLP-1 drugs. CagriSema may also preserve more lean muscle mass during weight loss compared to GLP-1-only drugs, though this requires further study.
For detailed comparisons of available drugs, see our retatrutide vs tirzepatide comparison and our complete retatrutide guide.
Side Effects
Cagrilintide and CagriSema side effects follow the same pattern as other injectable weight loss drugs. GI events are the most common and are dose-dependent.
| Side Effect | CagriSema (REDEFINE 1) | Semaglutide alone |
|---|---|---|
| Any GI event | 79.6% | ~74% |
| Nausea | ~45% | ~44% |
| Diarrhea | ~25% | ~30% |
| Vomiting | ~22% | ~24% |
| Constipation | ~15% | ~24% |
| Injection site reactions | ~10% | ~5% |
Most GI side effects are classified as mild and transient. They peak during dose escalation (the first 16 weeks) and improve significantly at stable maintenance doses. The injection site reaction rate is higher for CagriSema than semaglutide alone, likely because two separate injections are required.
Serious adverse events were rare in the REDEFINE trials. Acute pancreatitis, gallbladder events, and kidney events occurred at rates similar to semaglutide monotherapy.
For managing similar side effects with available GLP-1 medications, see our guides on semaglutide nausea and tirzepatide constipation.
When Will CagriSema Be Available?
Novo Nordisk filed its New Drug Application (NDA) with the FDA for CagriSema on December 18, 2025. The FDA review is expected through 2026, with approval possible in late 2026 or 2027.
If approved, CagriSema would be the first combination obesity drug targeting both amylin and GLP-1 pathways. It would compete directly with tirzepatide (Zepbound) and provide an alternative mechanism for patients who do not achieve adequate results with existing GLP-1 drugs.
Novo Nordisk is also pursuing standalone cagrilintide through the RENEW Phase 3 programme, launched in Q4 2025. If successful, cagrilintide could become the first pure amylin-based obesity treatment, offering an option for patients who cannot tolerate GLP-1 drugs.
Pricing is not yet announced, but given Novo Nordisk's pricing for Wegovy ($1,349/month list price), CagriSema will likely carry a premium. Insurance coverage negotiations will be a major factor in real-world accessibility.
For patients seeking treatment now, semaglutide and tirzepatide are the FDA-approved options. Use our semaglutide dosage calculator or tirzepatide dosage calculator for dosing information.
Frequently Asked Questions
What is cagrilintide?
Cagrilintide (AM833/NN9838) is a long-acting amylin receptor agonist developed by Novo Nordisk. It mimics amylin, a hormone released from the pancreas alongside insulin that signals fullness to the brain. Its half-life is 159 to 195 hours, allowing once-weekly injection (PMID 33894838). It is combined with semaglutide in the product CagriSema.
How much weight can you lose on CagriSema?
CagriSema produced 22.7% mean body weight loss at 68 weeks in the REDEFINE 1 trial. 60% of participants achieved 20%+ loss, and 23% achieved 30%+ loss. For a person starting at 250 pounds, 22.7% equals roughly 57 pounds. Cagrilintide alone produces 11.8% weight loss at 68 weeks.
What is the cagrilintide dosage?
The standard cagrilintide titration starts at 0.25 mg/week and increases every 4 weeks: 0.25 mg (weeks 1-4), 0.5 mg (5-8), 1.0 mg (9-12), 1.7 mg (13-16), then 2.4 mg maintenance (week 17+). All doses are given as once-weekly subcutaneous injections.
Is cagrilintide FDA-approved?
No. Cagrilintide is not yet FDA-approved as of March 2026. Novo Nordisk filed a New Drug Application for CagriSema on December 18, 2025. FDA decision is expected in 2026 or 2027. It is not available for prescription outside of clinical trials.
How is cagrilintide different from semaglutide?
Cagrilintide targets AMY1R and AMY3R amylin receptors in the hypothalamus, while semaglutide targets GLP-1 receptors in the gut and brainstem. They work through independent appetite pathways. Cagrilintide affects both homeostatic hunger (physical need) and hedonic hunger (cravings). Together as CagriSema, they produce more weight loss than either drug alone.
How does CagriSema compare to tirzepatide?
In the head-to-head REDEFINE 4 trial, CagriSema produced 23.0% weight loss versus tirzepatide 15 mg at 25.5% over 68 weeks. The primary noninferiority endpoint was not met. The open-label design is a caveat. The mechanisms differ: amylin + GLP-1 (CagriSema) versus GLP-1 + GIP (tirzepatide). Patients who do not respond to one may respond to the other.
Can cagrilintide be used without semaglutide?
Cagrilintide monotherapy produced 11.8% weight loss at 68 weeks in a Phase 3 trial, compared to 2.3% with placebo. The combination with semaglutide (CagriSema) roughly doubles this to 22.7%. Novo Nordisk launched the RENEW Phase 3 programme to pursue regulatory approval for standalone cagrilintide.
What are the most common side effects of cagrilintide?
Gastrointestinal events are most common: nausea (20-47% depending on dose), constipation, diarrhea, and vomiting. Most are mild and transient, peaking during dose escalation. Only 1.0% discontinued due to nausea in the monotherapy Phase 3 trial. Cagrilintide shows lower vomiting rates than semaglutide or liraglutide.
The Bottom Line
Cagrilintide represents a genuinely new approach to obesity treatment. By targeting the amylin pathway alongside GLP-1, CagriSema produced 22.7% weight loss in REDEFINE 1, while the head-to-head REDEFINE 4 trial showed 23.0% for CagriSema versus 25.5% for tirzepatide. Cagrilintide monotherapy delivered 11.8% weight loss with notably low discontinuation rates. These results establish amylin agonism as a viable therapeutic pathway, whether combined with GLP-1 or used alone.
The REDEFINE 2 trial confirmed CagriSema's benefit in type 2 diabetes: 13.7% weight loss and 73.5% of patients reaching HbA1c at or below 6.5% (PMID 40544432). Novo Nordisk filed its NDA on December 18, 2025, with FDA decision expected in 2026 or 2027. The RENEW programme will determine whether standalone cagrilintide earns its own approval.
For patients seeking treatment now, semaglutide and tirzepatide remain the FDA-approved options. Use our semaglutide dosage calculator or explore our complete guides on how semaglutide works and tirzepatide results.
This is educational content based on published clinical trial data and Novo Nordisk regulatory filings. It is not medical advice. Consult a healthcare provider before starting any weight loss medication.
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