Cagrilintide (NN9838)
Long-acting amylin analogue (Novo Nordisk), studied alone and co-administered with semaglutide as CagriSema. CagriSema was submitted to the US FDA in December 2025; not approved.
60-Second Scientific Briefing
Cagrilintide is a long-acting, once-weekly analogue of amylin, a hormone released with insulin that promotes fullness. Novo Nordisk studies it alone and together with semaglutide as CagriSema. CagriSema was submitted to the US FDA in December 2025 and is not approved. In REDEFINE 1 (NEJM 2025, 3,417 adults, 68 weeks) mean weight change was −20.4% with CagriSema against −3.0% with placebo. In REDEFINE 4 it did not show non-inferiority to tirzepatide.
What is Cagrilintide?
Pharmacological Classification & Molecular IdentityCagrilintide is a long-acting analogue of amylin, a pancreatic hormone co-secreted with insulin that promotes satiety and slows gastric emptying. It is given by once-weekly subcutaneous injection, alone or with semaglutide (CagriSema). [1] The Lancet, 2021 ↗
Verified Chemical & Regulatory Registry Identifiers
Mechanism of Action & Receptor Targets
Biological Pathway and Target BindingReceptor Selectivity: Activates amylin receptors and the calcitonin receptor (it is described as a non-selective amylin receptor agonist). Combined with semaglutide, it adds amylin signalling to GLP-1 receptor signalling. [1] Mol Metab, 2025 ↗ [2] The Lancet, 2021 ↗
Regulatory & FDA Approval Status
Legal and Regulatory ClassificationsNot approved. Novo Nordisk submitted CagriSema (cagrilintide co-administered with semaglutide) to the US FDA for weight management in December 2025, based on REDEFINE 1 and REDEFINE 2, and stated that a decision was expected by late 2026. Cagrilintide alone is not approved anywhere. [1] Novo Nordisk A/S (company announcement, SEC Form 6-K), 2026 ↗
Cagrilintide is not approved for commercial sale, prescription therapy, or compounded medication distribution. It exists strictly within authorized scientific and clinical research frameworks.
Human Evidence & Clinical Trials
Clinical Study Readouts and Evidence SynthesesPhase 2, cagrilintide alone (Lancet 2021): 706 adults without diabetes on five once-weekly doses vs placebo and liraglutide for 26 weeks; weight loss 6.0–10.8% vs 3.0% with placebo, and the highest dose lost more than liraglutide 3.0 mg (10.8% vs 9.0%). REDEFINE 1 (NEJM 2025): 3,417 adults without diabetes; CagriSema −20.4% vs −3.0% with placebo at 68 weeks. REDEFINE 2 (NEJM 2025): 1,206 adults with type 2 diabetes; −13.7% vs −3.4% at 68 weeks, and HbA1c of 6.5% or less in 73.5% vs 15.9%. REDEFINE 4 (company announcement, February 2026): open-label, 809 participants, 84 weeks vs tirzepatide 15 mg; −20.2% vs −23.6% (treatment-regimen analysis), so non-inferiority was not shown. [1] N Engl J Med, 2025 ↗ [2] N Engl J Med, 2025 ↗ [3] The Lancet, 2021 ↗ [4] Novo Nordisk A/S (company announcement, SEC Form 6-K), 2026 ↗
Clinical Evidence
Phase 2, cagrilintide alone (Lancet 2021): 706 adults without diabetes on five once-weekly doses vs placebo and liraglutide for 26 weeks; weight loss 6.0–10.8% vs 3.0% with placebo, and the highest dose lost more than liraglutide 3.0 mg (10.8% vs 9.0%). REDEFINE 1 (NEJM 2025): 3,417 adults without diabetes; CagriSema −20.4% vs −3.0% with placebo at 68 weeks. REDEFINE 2 (NEJM 2025): 1,206 adults with type 2 diabetes; −13.7% vs −3.4% at 68 weeks, and HbA1c of 6.5% or less in 73.5% vs 15.9%. REDEFINE 4 (company announcement, February 2026): open-label, 809 participants, 84 weeks vs tirzepatide 15 mg; −20.2% vs −23.6% (treatment-regimen analysis), so non-inferiority was not shown.
Safety Profile & Clinical Limitations
Documented Adverse Events and Known UncertaintiesGastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation, abdominal pain) were the most common and mainly transient and mild to moderate: 79.6% vs 39.9% with placebo in REDEFINE 1, and 72.5% vs 34.4% in REDEFINE 2. With cagrilintide alone (phase 2), gastrointestinal events occurred in 41–63% vs 32% with placebo, mainly nausea (20–47% vs 18%), plus administration-site reactions. [1] N Engl J Med, 2025 ↗ [2] N Engl J Med, 2025 ↗ [3] The Lancet, 2021 ↗
Long-term safety beyond the trial periods, cardiovascular outcomes, and the regulatory decision are pending. In the head-to-head REDEFINE 4 trial, CagriSema did not show non-inferiority to tirzepatide. [1] Novo Nordisk A/S (company announcement, SEC Form 6-K), 2026 ↗
Dose Approval Status
Commercial Dosing Status and Policy DirectivesNo dose is approved. The dose groups used in the trials are part of each trial's design and are described in the linked publications; they are not a recommendation. [1] N Engl J Med, 2025 ↗
Under Egypt Peptides medical governance policies, no personal dosages, titration intervals, cycles, stacking recommendations, or self-injection instructions may be provided for unapproved investigational compounds. Clinical study protocols represent controlled experimental research parameters exclusively.
What is Known vs. What is Unknown
Evidence Comparison and Clinical Evidence Boundaries✓ Confirmed Scientific Evidence
- Cagrilintide is a long-acting analogue of amylin, a pancreatic hormone co-secreted with insulin that promotes satiety and slows gastric emptying. It is given by once-weekly subcutaneous injection, alone or with semaglutide (CagriSema).
- Targets & Selectivity: Activates amylin receptors and the calcitonin receptor (it is described as a non-selective amylin receptor agonist). Combined with semaglutide, it adds amylin signalling to GLP-1 receptor signalling.
- Phase 2, cagrilintide alone (Lancet 2021): 706 adults without diabetes on five once-weekly doses vs placebo and liraglutide for 26 weeks; weight loss 6.0–10.8% vs 3.0% with placebo, and the highest dose lost more than liraglutide 3.0 mg (10.8% vs 9.0%). REDEFINE 1 (NEJM 2025): 3,417 adults without diabetes; CagriSema −20.4% vs −3.0% with placebo at 68 weeks. REDEFINE 2 (NEJM 2025): 1,206 adults with type 2 diabetes; −13.7% vs −3.4% at 68 weeks, and HbA1c of 6.5% or less in 73.5% vs 15.9%. REDEFINE 4 (company announcement, February 2026): open-label, 809 participants, 84 weeks vs tirzepatide 15 mg; −20.2% vs −23.6% (treatment-regimen analysis), so non-inferiority was not shown.
- Safety considerations: Gastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation, abdominal pain) were the most common and mainly transient and mild to moderate: 79.6% vs 39.9% with placebo in REDEFINE 1, and 72.5% vs 34.4% in REDEFINE 2. With cagrilintide alone (phase 2), gastrointestinal events occurred in 41–63% vs 32% with placebo, mainly nausea (20–47% vs 18%), plus administration-site reactions.
? Unknown / Under Ongoing Investigation
- Long-term safety beyond the trial periods, cardiovascular outcomes, and the regulatory decision are pending. In the head-to-head REDEFINE 4 trial, CagriSema did not show non-inferiority to tirzepatide.
Verified Questions & Answers
10 Verified scientific answers with permanent anchor keysCagrilintide is a long-acting, once-weekly analogue of the hormone amylin, which promotes fullness. Novo Nordisk studies it alone and with semaglutide as CagriSema.
It activates amylin receptors and the calcitonin receptor, which promote satiety and slow stomach emptying. In CagriSema this is combined with GLP-1 receptor activation by semaglutide.
- Eloralintide (LY3841136), a novel amylin receptor agonist: from discovery to clinical proof of concept (receptor selectivity compared with cagrilintide) (Mol Metab, 2025-12-01)
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial (The Lancet, 2021-12-11)
No. CagriSema was submitted to the US FDA in December 2025 and the company expected a decision by late 2026. Cagrilintide alone is not approved anywhere.
- CagriSema REDEFINE 4 head-to-head results; US submission status (Novo Nordisk A/S (company announcement, SEC Form 6-K), 2026-02-23)
REDEFINE 1 (NEJM 2025, 3,417 adults): CagriSema −20.4% vs −3.0% with placebo at 68 weeks. REDEFINE 2 (1,206 adults with type 2 diabetes): −13.7% vs −3.4%. REDEFINE 4: did not show non-inferiority to tirzepatide.
Phase 2, cagrilintide alone (Lancet 2021): 706 adults without diabetes received one of five once-weekly cagrilintide doses, 101 placebo and 99 liraglutide 3.0 mg daily, for 26 weeks; weight loss was 6.0–10.8% vs 3.0% with placebo, and the highest dose lost more than liraglutide (10.8% vs 9.0%). REDEFINE 1 (NEJM 2025): 3,417 adults with overweight or obesity without diabetes (2,108 on CagriSema); at 68 weeks mean weight change was −20.4% vs −3.0% with placebo. REDEFINE 2 (NEJM 2025): 1,206 adults with type 2 diabetes and a BMI of 27 or more, randomised 3:1; −13.7% vs −3.4% at 68 weeks, and 73.5% vs 15.9% reached an HbA1c of 6.5% or less. REDEFINE 4 (Novo Nordisk announcement, February 2026): an open-label trial in 809 participants over 84 weeks against tirzepatide 15 mg; −20.2% vs −23.6% in the treatment-regimen analysis, so the primary end point of non-inferiority was not met.
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1) (N Engl J Med, 2025-08-14)
- Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2) (N Engl J Med, 2025-08-14)
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial (The Lancet, 2021-12-11)
- CagriSema REDEFINE 4 head-to-head results; US submission status (Novo Nordisk A/S (company announcement, SEC Form 6-K), 2026-02-23)
Mostly gastrointestinal adverse events, mainly transient and mild to moderate: 79.6% vs 39.9% with placebo in REDEFINE 1 and 72.5% vs 34.4% in REDEFINE 2. With cagrilintide alone, nausea occurred in 20–47% vs 18%, and administration-site reactions were also common.
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1) (N Engl J Med, 2025-08-14)
- Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2) (N Engl J Med, 2025-08-14)
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial (The Lancet, 2021-12-11)
Long-term safety, cardiovascular outcomes and the FDA decision are pending. In REDEFINE 4, CagriSema did not show non-inferiority to tirzepatide.
- CagriSema REDEFINE 4 head-to-head results; US submission status (Novo Nordisk A/S (company announcement, SEC Form 6-K), 2026-02-23)
No dose is approved. The trial dose groups are part of each trial's design and are described in the linked publications; they are not a recommendation.
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1) (N Engl J Med, 2025-08-14)
There is no approved product label, so no official storage instructions exist outside the clinical trials, where the sponsor supplies the investigational product and its storage conditions.
It is not named individually on the 2026 WADA Prohibited List. Under section S0 (non-approved substances), any pharmacological substance without a current approval by a government health authority for human therapeutic use is prohibited at all times, so the investigational compound falls under S0 until it is approved. Athletes should confirm with their national anti-doping organisation.
- WADA Prohibited List (World Anti-Doping Agency)
Egypt Peptides publishes reviewed scientific reference monographs for documentation and research. The site does not give individual medical advice, preparation or injection instructions, combination protocols or off-label use instructions. Decisions about any medicine belong to the treating physician.
Authoritative Sources & Literature Registry
Regulatory dossiers, clinical trial registries, and published studiesEloralintide (LY3841136), a novel amylin receptor agonist: from discovery to clinical proof of concept (receptor selectivity compared with cagrilintide) ↗
https://pubmed.ncbi.nlm.nih.gov/41109426/
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1) ↗
https://pubmed.ncbi.nlm.nih.gov/40544433/
Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2) ↗
https://pubmed.ncbi.nlm.nih.gov/40544432/
Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial ↗
https://pubmed.ncbi.nlm.nih.gov/34798060/
CagriSema REDEFINE 4 head-to-head results; US submission status ↗
https://www.sec.gov/Archives/edgar/data/353278/000117184326000996/f6k_022326.htm