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AMIRAVOResearch Library

Semaglutide vs cagrilintide

Semaglutide is an FDA-approved GLP-1 receptor agonist, while cagrilintide is an investigational long-acting amylin analogue that also activates calcitonin receptors 1,2,3,4. The two are developed by the same company and are being studied together as a combination called CagriSema 5. Their side-by-side evidence comes mainly from trials in which each was given alone in separate arms, including a 92-person phase 2 trial in type 2 diabetes 6.

Unbranded reference vial illustrating Semaglutide; not an actual product
Semaglutide
FDA-approved
Unbranded reference vial illustrating Cagrilintide; not an actual product
Cagrilintide
Investigational

Side by side

FieldSemaglutideCagrilintide
ClassGLP-1 receptor agonist 1Long-acting amylin analogue; amylin and calcitonin receptor agonist (investigational) 3,4
Origin and structureGLP-1 analogue with 94% sequence homology to human GLP-1; lysine 26 carries a C18 fatty diacid for albumin binding and position 8 is modified against DPP-4 breakdown 1Stable, lipidated analogue of the pancreatic hormone amylin, developed to avoid amylin's tendency to form amyloid fibrils 7
Proposed mechanismActivates the GLP-1 receptor; in animal studies it reached and activated brain regions involved in food intake 1Solved receptor structures show an amylin-like binding mode at amylin receptors 1 to 3 and the calcitonin receptor 4; in mice, body-weight effects depended on amylin receptors 1 and 3 8
Half-lifeAbout 1 week per the FDA labels 1,9159 to 195 hours in a phase 1b trial in which it was co-administered with semaglutide 10
Highest human trial phaseApproved; phase 3 and cardiovascular outcome trials published 11,12Phase 3 (alone as a comparator arm and in combination with semaglutide); 22 phase 3 registry entries 5,13
FDA statusApproved as Ozempic (5 December 2017) and Wegovy (4 June 2021), per Drugs@FDA as of 24 October 2026 2Not approved; no Drugs@FDA application record as of 24 October 2026 14
Published human outcomesSTEP 1: -14.9% vs -2.4% body-weight change at 68 weeks 11; SELECT: major adverse cardiovascular events hazard ratio 0.80 in people with cardiovascular disease and overweight or obesity 12Phase 2 obesity trial: -6.0% to -10.8% vs -3.0% with placebo at 26 weeks 3; phase 2 type 2 diabetes trial: -8.1% body weight and -0.9 percentage points HbA1c at 32 weeks 6
Safety signalsBoxed warning for thyroid C-cell tumours seen in rodents; gastrointestinal reactions most common 1; higher rate of diabetic retinopathy complications in SUSTAIN-6 (hazard ratio 1.76) 15Gastrointestinal events (nausea 20% to 47% vs 18% with placebo) and administration-site reactions 3; a meta-analysis reported more serious adverse events than with semaglutide (risk ratio 1.83) 16
WADA statusNot named on the 2026 Prohibited List 17; WADA said in September 2026 that the status of GLP-1 receptor agonists is unchanged for 2027 18Not named on the 2026 Prohibited List; class S0 covers substances with no current approval by any governmental health authority, such as drugs under clinical development 17
Who funded the evidenceNovo Nordisk funded STEP 1, SELECT and FLOW 11,12,19Novo Nordisk funded the phase 1b, phase 2 and phase 3 trials reviewed 3,5,10

Semaglutide: what the data says

Semaglutide is approved by the FDA for type 2 diabetes, cardiovascular and kidney risk reduction in specified groups, chronic weight management and, under accelerated approval, MASH with moderate to advanced fibrosis 1,9.

  • In STEP 1 (1961 adults without diabetes; human data), mean body-weight change at 68 weeks was -14.9% vs -2.4% with placebo; discontinuation due to gastrointestinal events was 4.5% vs 0.8% 11.
  • In SELECT (17,604 adults with cardiovascular disease and overweight or obesity; human data), the primary cardiovascular outcome occurred in 6.5% vs 8.0% (hazard ratio 0.80) 12.
  • In FLOW (3533 people with type 2 diabetes and chronic kidney disease; human data), the risk of major kidney disease events was 24% lower than with placebo 19.

Cagrilintide: what the data says

Cagrilintide has been tested alone in phase 1 to 2 trials and as a comparator arm in phase 3 trials of the cagrilintide-semaglutide combination 3,5,10.

  • In a 26-week phase 2 trial (706 participants on cagrilintide; human data), mean body-weight change was -6.0% to -10.8% across doses vs -3.0% with placebo; the highest dose differed from liraglutide by 1.8 percentage points 3.
  • In mice (animal data), removing amylin receptors 1 and 3 reduced cagrilintide's effect on body weight 8.
  • In REDEFINE 1 (3417 participants; human data), the combination with semaglutide produced a mean body-weight change of -20.4% vs -3.0% with placebo at 68 weeks; gastrointestinal adverse events affected 79.6% vs 39.9% 5.

Key research differences

  • Hormone family: semaglutide mimics GLP-1, whereas cagrilintide mimics amylin and also acts at the calcitonin receptor 1,4.
  • Regulatory status: semaglutide has been FDA-approved since 2017, while cagrilintide had no Drugs@FDA record as of 24 October 2026 2,14.
  • Direct comparison: in a 32-week phase 2 trial in type 2 diabetes, body weight changed by -5.1% with semaglutide and -8.1% with cagrilintide, while HbA1c changed by -1.8 and -0.9 percentage points 6.
  • Outcome evidence: semaglutide has published cardiovascular and kidney outcome trials, whereas the cagrilintide trials reviewed report body weight, glycaemic and safety measures 3,12,19.
  • Safety reporting: a 2026 meta-analysis found cagrilintide alone had a higher risk of serious adverse events than semaglutide (risk ratio 1.83), with similar body-weight change 16.

Where the evidence is limited

The only direct comparisons identified are small or secondary: a 92-person phase 2 trial in type 2 diabetes and comparator arms within combination trials, whose abstracts do not report the single-drug arms against each other 5,6,20. A meta-analysis pooled only three trials 16. All of the cagrilintide trials and the main semaglutide trials were funded by Novo Nordisk, which develops both 3,11. Cagrilintide's half-life was measured only while it was given with semaglutide 10.

Frequently asked questions

Does semaglutide lead to more body-weight change than cagrilintide?
Comparisons are limited. In one 32-week phase 2 trial in type 2 diabetes, cagrilintide arms showed a larger body-weight change and semaglutide arms a larger HbA1c change 6; a meta-analysis found body-weight change comparable between the two 16.
Is cagrilintide FDA-approved?
No. An openFDA query of Drugs@FDA on 24 October 2026 returned no application record for cagrilintide 14. It remains in phase 3 trials 13.
What is CagriSema?
CagriSema is the co-administration of cagrilintide and semaglutide. In REDEFINE 1, it was compared with placebo and with each drug alone in adults with overweight or obesity 5.
Can semaglutide and cagrilintide be compared directly?
Only partly. Both were given alone in separate arms of a phase 2 type 2 diabetes trial and of phase 3 combination trials, but those trials were designed to test the combination 6,20.

References

  1. WEGOVY (semaglutide) injection and tablets: prescribing information, DailyMed set ID ee06186f-2aa3-4990-a760-757579d8f77b (label version dated 18 June 2026) FDA label (via openFDA). 2026
  2. Drugs@FDA application records for NDA 215866 (Mounjaro), NDA 217806 (Zepbound), NDA 209637 (Ozempic), NDA 215256 (Wegovy), NDA 022341 (Victoza) and NDA 206321 (Saxenda): original approval dates (queried 24 October 2026) Drugs@FDA (via openFDA). 2026
  3. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial Lancet. 2021
  4. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors Nat Commun. 2025
  5. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1) N Engl J Med. 2025
  6. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial Lancet. 2023
  7. Development of Cagrilintide, a Long-Acting Amylin Analogue J Med Chem. 2021
  8. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3 EBioMedicine. 2025
  9. OZEMPIC (semaglutide) injection: prescribing information, DailyMed set ID adec4fd2-6858-4c99-91d4-531f5f2a2d79 (label version dated 1 June 2026) FDA label (via openFDA). 2026
  10. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial Lancet. 2021
  11. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) N Engl J Med. 2021
  12. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) N Engl J Med. 2023
  13. ClinicalTrials.gov registry search for cagrilintide as intervention (44 records, 22 phase 3; retrieved 24 October 2026) ClinicalTrials.gov. 2026
  14. Drugs@FDA application data queried through openFDA for cagrilintide (no matching application record returned on 24 October 2026) openFDA / Drugs@FDA. 2026
  15. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) N Engl J Med. 2016
  16. Efficacy and Safety of Cagrilintide and Cagrisema Versus Semaglutide as Anti-Obesity Medications: A Systematic Review, Meta-Analysis and Meta-Regression Diabetes Obes Metab. 2026
  17. The 2026 Prohibited List - World Anti-Doping Code, as published in the Netherlands Treaty Series (Tractatenblad 2026, 25; Council of Europe Anti-Doping Convention appendix, in force 1 January 2026) Tractatenblad (Official Publications of the Kingdom of the Netherlands). 2026
  18. WADA publishes 2027 Prohibited List (news release, 21 September 2026) World Anti-Doping Agency. 2026
  19. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW) N Engl J Med. 2024
  20. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study Lancet Diabetes Endocrinol. 2026

For research use only. Not for human or veterinary use. Not a drug, food, or dietary supplement. This page compares published research and is not medical advice or a recommendation.