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Investigational peptide combinationHuman trialsIn clinical trials

CagriSema

Cagrilintide and semaglutide

Last reviewed October 27, 2026 · 14 sources · Written for general readers · Compare with another compound →

The bottom line

CagriSema combines the amylin copy cagrilintide with semaglutide in one weekly shot. In a 68 week trial of 3,417 adults it led to 20.4% weight loss versus 3.0% on placebo, but it fell short of tirzepatide head to head, and 4 in 5 people had stomach side effects. It is under FDA review and not approved, so any version sold now is unregulated.

Where the evidence stands

What it is

CagriSema is an experimental weekly shot from Novo Nordisk that combines two drugs: cagrilintide, a long acting copy of the fullness hormone amylin, and semaglutide, the GLP-1 drug in Wegovy and Ozempic.[1]

Novo Nordisk asked FDA to approve it for weight loss and keeping weight off in December 2025. It is not approved in the US or the EU. If approved, Novo says it would be the first combination shot of a GLP-1 drug and an amylin copy.[1]

Because it is a mix of two separate molecules, it has no single formula or CAS number.

Name
CagriSema (Cagrilintide and semaglutide)
Other names
cagrilintide plus semaglutide
Type
Investigational peptide combination

How it works

CagriSema works on two separate fullness signals at the same time.[1]

  • Semaglutide switches on the GLP-1 receptor, which is found in brain areas that control hunger.[2]
  • Cagrilintide mimics amylin, a pancreas hormone that promotes fullness.[3] In mice it acts on amylin receptors in the brainstem.[4]
  • In trials, the two together led to more weight loss than either one alone.[5][6]

The combination clearly adds to semaglutide alone, but how the two parts work together in people is still being studied.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Animal work explains the amylin half

  • In obese mice, cagrilintide alone cut food intake in the first days and led to weight loss over 3 weeks.[4]
  • Mice lacking two amylin receptor parts responded less, which suggests these receptors drive the effect.[4]
  • Cagrilintide switched on brainstem areas tied to fullness and nausea.[4]

Limit: We found no published animal study of the full combination; human trials are the main evidence.

Human studies

Large phase 3 trials show strong weight loss with common side effects

  • Phase 1b: 96 adults with overweight or obesity got semaglutide plus cagrilintide or placebo for 20 weeks. At the higher cagrilintide strengths, weight fell about 15% to 17% versus about 8% to 10% with semaglutide alone.[13]
  • Phase 2 diabetes trial: 92 adults with type 2 diabetes were treated for 32 weeks. Weight fell 15.6% on CagriSema versus 5.1% on semaglutide and 8.1% on cagrilintide. Time spent in a healthy blood sugar range rose to about 89%.[6]
  • REDEFINE 1: 3,417 adults without diabetes were treated for 68 weeks. Weight fell 20.4% versus 3.0% on placebo. Gut side effects hit 79.6% versus 39.9%, mostly mild to moderate and short lived.[5]
  • REDEFINE 2: 1,206 adults with type 2 diabetes and excess weight were treated for 68 weeks. Weight fell 13.7% versus 3.4% on placebo. Gut side effects hit 72.5% versus 34.4%.[7]
  • REIMAGINE 2: 2,713 adults with type 2 diabetes were treated for 68 weeks. CagriSema lowered HbA1c a bit more than semaglutide alone. Side effects were reported by 86.9% on CagriSema, 81.2% on semaglutide and 70.5% on placebo.[8]
  • REDEFINE 4: in 809 adults over 84 weeks, CagriSema led to 23.0% weight loss versus 25.5% on tirzepatide.[10]
  • Quitting: side effects led 5.9% to stop in REDEFINE 1 and 8.4% in REDEFINE 2, versus about 3% to 3.5% on placebo.[1]

Limit: FDA has not finished its review, and the head to head trial with tirzepatide is so far reported only by the maker.

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Causes about 20% weight loss

Shown in people

REDEFINE 1 treated 3,417 adults with obesity or overweight and no diabetes for 68 weeks. Counting everyone, weight fell 20.4% on CagriSema versus 3.0% on placebo.[5] In REDEFINE 2, 1,206 adults with type 2 diabetes lost 13.7% versus 3.4%.[7]

Works better than semaglutide alone

Shown in people

REIMAGINE 2 treated 2,713 adults with type 2 diabetes for 68 weeks. HbA1c (a three month blood sugar average) fell 1.91 points on CagriSema versus 1.75 on semaglutide alone, a small but real difference.[8] The maker reported about 14% weight loss versus about 10% on semaglutide in people who stayed on treatment.[9]

Works as well as tirzepatide

No benefit in trials so far

REDEFINE 4 compared it head to head with tirzepatide in 809 adults over 84 weeks. CagriSema led to 23.0% weight loss versus 25.5% for tirzepatide, so it failed to show it was about as good.[10]

Controls blood sugar in type 2 diabetes

Shown in people

In REDEFINE 2, 73.5% of people on CagriSema reached an HbA1c of 6.5% or lower versus 15.9% on placebo.[7] In a 32 week trial of 92 adults, HbA1c fell 2.2 points versus 1.8 on semaglutide and 0.9 on cagrilintide alone.[6]

Works even better for women

Mixed results

Novo reported in October 2026 that women in REDEFINE 1 lost about 25% of their weight on average. This was a post hoc analysis, meaning it was not planned before the trial, so it is weaker evidence.[11]

The weight stays off after stopping

Not tested

We found no published results on what happens after people stop CagriSema.[5] In a separate trial of people who stopped semaglutide and switched to placebo, they regained more than half of the weight they had lost within a year.[12]

Known risks and side effects

  • Stomach and gut side effects are very common. Gut side effects such as nausea, vomiting, diarrhea, constipation and stomach pain happened in 79.6% of people on CagriSema versus 39.9% on placebo in REDEFINE 1, and in 72.5% versus 34.4% in REDEFINE 2.[5][7]
  • Some people quit. Side effects led 5.9% to stop in REDEFINE 1 and 8.4% in REDEFINE 2, versus about 3% to 3.5% on placebo.[1]
  • Known semaglutide risks. Its semaglutide part carries a boxed warning about thyroid C cell tumors seen in rodents, plus warnings about pancreatitis and gallbladder disease.[2]
  • Unregulated copies. FDA says cagrilintide cannot legally be compounded, so any CagriSema style product sold online or by a pharmacy is not the tested drug.[14]

Regulatory status

Today: CagriSema is investigational and under FDA review after a December 2025 filing, with a decision expected by late 2026.[1][10] We found no FDA decision announced as of late October 2026.[11]

  1. REDEFINE 1 and REDEFINE 2 results appeared in print in the New England Journal of Medicine.[5][7]
  2. Novo Nordisk submitted CagriSema to FDA for weight management, based on REDEFINE 1 and 2.[1]
  3. REIMAGINE 2 results showed more weight loss and lower blood sugar than semaglutide alone in type 2 diabetes.[9]
  4. REDEFINE 4 missed its main goal against tirzepatide. Novo said an FDA decision was expected by late 2026.[10]
  5. Novo presented an extra analysis of REDEFINE 1 in women at a medical meeting, with no regulatory decision announced.[11]

Sources

  1. Novo Nordisk. Novo Nordisk files for FDA approval of CagriSema. December 18, 2025. Company announcement
  2. Novo Nordisk. WEGOVY (semaglutide) injection and tablets: prescribing information. Revised 06/2026. FDA label
  3. Lau DCW, Erichsen L, Francisco AM, et al. 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;398(10317):2160-2172. PMID 34798060
  4. Carvas AO, Leuthardt A, Kulka P, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine. 2025;118:105836. PMID 40609154
  5. Garvey WT, Bluher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025;393(7):635-647. PMID 40544433
  6. Frias JP, Deenadayalan S, Erichsen L, et al. 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;402(10403):720-730. PMID 37364590
  7. Davies MJ, Bajaj HS, Broholm C, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025;393(7):648-659. PMID 40544432
  8. Buse JB, Bajaj HS, Dalskov SM, et al. 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;14(8):662-677. PMID 42251859
  9. Novo Nordisk. Company announcement: CagriSema shows superior HbA1c reduction and weight loss versus semaglutide in adults with type 2 diabetes in REIMAGINE 2. February 2, 2026. Company announcement
  10. Novo Nordisk. Company announcement: CagriSema achieved 23% weight loss in REDEFINE 4; primary endpoint not achieved. February 23, 2026. Company announcement
  11. Novo Nordisk. Newsroom: latest news (including October 20, 2026 item on a REDEFINE 1 post hoc analysis in women). Accessed October 29, 2026. Company newsroom
  12. Aronne LJ, Horn DB, le Roux CW, et al. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. Nat Med. 2026;32(7):2679-2687. PMID 42120723
  13. Enebo LB, Berthelsen KK, Kankam M, et al. 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;397(10286):1736-1748. PMID 33894838
  14. U.S. Food and Drug Administration. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. Content current as of October 1, 2026. FDA
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

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