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Cagrilintide vs semaglutide

B Cagrilintide Long-acting amylin receptor agonist (amylin analog) Investigational — not FDA-approved A Semaglutide GLP-1 receptor agonist (fatty-acid–modified GLP-1 analog) FDA-approved — Ozempic (2017), Rybelsus (2019), Wegovy (2021)

Residue Editorial Team · updated

In brief

Cagrilintide is an investigational long-acting amylin analog; semaglutide is an FDA-approved GLP-1 receptor agonist1FDAWEGOVY prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2024-04-23.. Studied together as CagriSema in REDEFINE 1, the combination reduced weight by 20.4% versus 3.0% with placebo at 68 weeks2PubMedCoadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT et al. N Engl J Med. 2025.. Alone, cagrilintide reduced weight by 6.0–10.8% in phase 23PubMedOnce-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. Lau DCW et al. Lancet. 2021.; semaglutide 2.4 mg alone reduced it by 14.9% in STEP 14PubMedOnce-Weekly Semaglutide in Adults with Overweight or Obesity. Wilding JPH et al. N Engl J Med. 2021..

How do Cagrilintide and Semaglutide compare at a glance?

Table 1. Cagrilintide and Semaglutide on the dimensions that matter most; every entry is cited.
DimensionCagrilintideSemaglutide
MechanismLong-acting amylin receptor agonist3GLP-1 receptor agonist5FDAOZEMPIC prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-07-30.
FDA statusInvestigational; no Drugs@FDA applicationApproved6FDADrugs@FDA: OZEMPIC (NDA209637). NOVO; original approval 2017-12-05; Prescription, Discontinued.,7FDADrugs@FDA: WEGOVY, WEGOVY HD, WEGOVY FLEXTOUCH (NDA215256). NOVO; original approval 2021-06-04; Prescription.
Half-life159–195 hours8PubMedSafety, 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. Enebo LB et al. Lancet. 2021.About 7 days9PubMedPharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Hall S et al. Clin Pharmacokinet. 2018.
Weight, alone−6.0% to −10.8% vs −3.0% (phase 2, 26 wk)3−14.9% vs −2.4% (STEP 1, 68 wk)4
Combined (CagriSema)REDEFINE 1: −20.4% vs −3.0%2REDEFINE 2 (T2D): −13.7% vs −3.4%10PubMedCagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. Davies MJ et al. N Engl J Med. 2025.
InteractionDid not alter semaglutide exposure8—
Evidence gradeBA

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Registry data · How we grade · Markdown + sources

Figure 1. Size of the research record, from PubMed and ClinicalTrials.gov at the data edition. Bars are scaled to the larger value in each row; volume is not quality.
PubMed records 121 5,706
Trial publications 15 341
Registered studies 44 785
Phase 3 studies 22 184

Cagrilintide Semaglutide

Which hormone systems do they act on?

Semaglutide mimics GLP-1, an incretin hormone11PubMedAbsorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Jensen L et al. Eur J Pharm Sci. 2017.. Cagrilintide is a long-acting analog of amylin, a different satiety-related hormone3. Because they act on separate receptor systems, they were developed as a fixed combination. In the phase 1b study that first paired them, cagrilintide's half-life was 159–195 hours and it did not change semaglutide exposure8.

What did each drug do alone?

In a phase 2 trial with 706 participants randomized to cagrilintide, weight fell 6.0–10.8% across doses of 0.3–4.5 mg versus 3.0% with placebo, with nausea in 20–47% versus 18%; the 4.5 mg dose outperformed the active comparator liraglutide 3.0 mg (10.8% vs 9.0%)3. Semaglutide 2.4 mg produced −14.9% versus −2.4% in STEP 1 at 68 weeks4. These were separate trials of different durations, so they do not rank the two.

What did the CagriSema combination do?

REDEFINE 1 randomized 3,417 adults with overweight or obesity; the combination produced −20.4% versus −3.0% with placebo at 68 weeks2. Participants were randomized 21:3:3:7, so the trial also included 302 people on cagrilintide 2.4 mg alone and 302 on semaglutide 2.4 mg alone — the closest thing to a direct comparison of the two molecules. The abstract reports only the combination-versus-placebo result, so we do not quote the single-agent figures here. REDEFINE 2, in 1,206 adults with type 2 diabetes, found −13.7% versus −3.4%, and 73.5% reached HbA1c ≤6.5% versus 15.9%10.

How do their safety records compare?

Gastrointestinal adverse events affected 79.6% on cagrilintide–semaglutide versus 39.9% on placebo in REDEFINE 1, mostly transient and mild to moderate2. Semaglutide alone in STEP 1 most commonly caused nausea and diarrhea, with 4.5% discontinuing for gastrointestinal events4.

Are they FDA-approved?

Semaglutide is FDA-approved in injectable and oral forms6,7,12FDADrugs@FDA: OZEMPIC, RYBELSUS (NDA213051). NOVO; original approval 2019-09-20; Prescription.. Cagrilintide, alone or in combination, had no Drugs@FDA application at our fetch.

Can you take cagrilintide and semaglutide together?

That combination is CagriSema. In REDEFINE 1 (3,417 adults with overweight or obesity) it reduced weight by 20.4% versus 3.0% with placebo at 68 weeks2. Cagrilintide alone is not FDA-approved; semaglutide is6,7.

Two identical glass beakers, one holding pale amber liquid and one clear, standing either side of a brass balance

Why do they get these evidence grades?

B Cagrilintide
Randomized phase 2 and phase 3 (REDEFINE) trials are published in The Lancet and NEJM; Drugs@FDA lists no approved application. Grade B: Randomized human trials.
A Semaglutide
FDA-approved as injection and tablet for type 2 diabetes, weight management and cardiovascular risk reduction; supported by large outcomes trials. Grade A: Approved / regulatory-grade.

Questions readers ask

What is CagriSema?

A once-weekly combination of cagrilintide and semaglutide 2.4 mg. In REDEFINE 1 (3,417 adults with overweight or obesity) it reduced weight by 20.4% versus 3.0% with placebo at 68 weeks2.

Is cagrilintide approved?

No. Drugs@FDA listed no cagrilintide application at our fetch. Semaglutide is approved as Ozempic, Rybelsus and Wegovy6,7.

Do they have the same side effects?

Gastrointestinal events are prominent with both. In REDEFINE 1, 79.6% on the combination reported gastrointestinal adverse events versus 39.9% on placebo, mainly transient and mild to moderate2.

Can you take cagrilintide and semaglutide together?

Yes, that combination is CagriSema. In REDEFINE 1 it reduced weight by 20.4% versus 3.0% with placebo at 68 weeks2. Cagrilintide alone is not FDA-approved; semaglutide is6,7.

Is cagrilintide better than semaglutide for weight loss?

Alone, phase 2 cagrilintide reduced weight by 6.0–10.8%3, less than semaglutide 2.4 mg in STEP 1 (−14.9%)4. Combined as CagriSema the reduction was larger than either alone in REDEFINE 12.

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

  1. 1 FDA WEGOVY prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2024-04-23.
  2. 2 PubMed Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2025. PMID 40544433; doi:10.1056/NEJMoa2502081.
  3. 3 PubMed 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. PMID 34798060; doi:10.1016/S0140-6736(21)01751-7.
  4. 4 PubMed Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021. PMID 33567185; doi:10.1056/NEJMoa2032183.
  5. 5 FDA OZEMPIC prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-07-30.
  6. 6 FDA Drugs@FDA: OZEMPIC (NDA209637). NOVO; original approval 2017-12-05; Prescription, Discontinued.
  7. 7 FDA Drugs@FDA: WEGOVY, WEGOVY HD, WEGOVY FLEXTOUCH (NDA215256). NOVO; original approval 2021-06-04; Prescription.
  8. 8 PubMed 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. PMID 33894838; doi:10.1016/S0140-6736(21)00845-X.
  9. 9 PubMed Hall S, Isaacs D, Clements JN. Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Clin Pharmacokinet 2018. PMID 29915923; doi:10.1007/s40262-018-0668-z.
  10. 10 PubMed 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. PMID 40544432; doi:10.1056/NEJMoa2502082.
  11. 11 PubMed Jensen L, Helleberg H, Roffel A, et al. Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci 2017. PMID 28323117; doi:10.1016/j.ejps.2017.03.020.
  12. 12 FDA Drugs@FDA: OZEMPIC, RYBELSUS (NDA213051). NOVO; original approval 2019-09-20; Prescription.