CagriSema is an investigational once-weekly injection that combines cagrilintide 2.4 mg — a long-acting amylin analog — with semaglutide 2.4 mg, the GLP-1 receptor agonist sold as Wegovy. In the Phase 3 REDEFINE 1 trial it produced 20.4% mean weight loss over 68 weeks (treatment-policy estimand) versus 3.0% for placebo.
Developed by Novo Nordisk, CagriSema is not a single molecule and not an approved product: its US application entered FDA review after a December 2025 filing, with a decision expected in late 2026. It also is not sold on the research-peptide market as "CagriSema" — only its two component compounds are available separately, which makes evidence honesty and sourcing verification the two things a buyer most needs. This guide covers what the trials actually show, how CagriSema compares to tirzepatide, and how to verify the component peptides against Peptigrity's independent weight-loss and metabolic peptide data.
What is CagriSema?
CagriSema is an investigational, once-weekly subcutaneous injectable that pairs two peptides in a single fixed-dose formulation: cagrilintide 2.4 mg and semaglutide 2.4 mg. It is not one molecule but two separate hormones that suppress appetite through different receptor systems. Developed by Novo Nordisk, CagriSema has no single molecular weight or CAS number because it is a co-formulation, not a novel compound. As of July 2026 it is not approved anywhere, and its US application is under FDA review.
The design goal is straightforward: stack two appetite-regulating pathways that work independently, so the combined effect exceeds what either hormone delivers alone. Cagrilintide (development code AM833, also NN9838) is a synthetic long-acting analog of amylin, a pancreatic hormone co-secreted with insulin. Semaglutide is the same GLP-1 receptor agonist already marketed as Wegovy (for obesity) and Ozempic (for type 2 diabetes). Novo Nordisk packages the two at a fixed 2.4 mg/2.4 mg ratio for a single weekly injection.
How does CagriSema work? The amylin + GLP-1 dual mechanism
CagriSema works by combining two gut hormones — amylin and GLP-1 — that curb appetite through separate, non-overlapping receptor systems, producing additive weight loss. Cagrilintide activates amylin receptors in the area postrema of the brainstem, while semaglutide activates GLP-1 receptors concentrated in the nucleus tractus solitarius and hypothalamus. Because the two act on distinct central circuits, their effects add together rather than compete — a hypothesis first confirmed in a Phase 1b human trial that showed the combination drove more weight loss than either agent alone.
What does cagrilintide (the amylin analog) do?
Cagrilintide is a long-acting acylated amylin analog — more precisely a dual amylin and calcitonin receptor agonist — built on a 37-amino-acid backbone with an N-terminal C20 fatty-diacid chain that binds serum albumin and extends its elimination half-life to roughly 159–195 hours (about 7 days), enabling once-weekly dosing. Native amylin has a half-life of only about 4 minutes; the earlier approved amylin analog pramlintide required three daily injections. Cagrilintide acts centrally to reduce food intake, slow gastric emptying, and increase satiety. In a Phase 2 monotherapy trial, cagrilintide 4.5 mg produced roughly 10.8% weight loss at 26 weeks — evidence classified as a human randomized controlled trial. You can read the full amylin mechanism in the cagrilintide amylin-weight-loss science breakdown.
What does semaglutide (the GLP-1 agonist) add?
Semaglutide contributes an established GLP-1 receptor agonist effect — appetite suppression, slowed gastric emptying, and improved glycemic control — that already carries proven weight-loss and cardiovascular benefit at the 2.4 mg dose. As monotherapy, semaglutide 2.4 mg produces mid-teens percentage weight loss in obesity trials, and it is one of the most extensively studied peptides in the metabolic field. Its role in CagriSema is to supply the GLP-1 half of the dual mechanism while cagrilintide supplies the amylin half. The semaglutide weight-loss and safety science article covers the GLP-1 pathway in depth.
Why combine them?
Combining amylin and GLP-1 agonism is mechanistically rational because the two hormones signal through anatomically separate appetite circuits, so their satiety effects are additive rather than redundant. The Phase 1b proof-of-concept — a randomized, placebo-controlled trial of cagrilintide plus semaglutide 2.4 mg led by Enebo and colleagues — demonstrated that co-administration reduced body weight beyond either agent alone, with a tolerability profile that justified advancing the combination into Phase 3. This is the scientific basis for the entire REDEFINE program.
What did the REDEFINE trials show?
The Phase 3 REDEFINE program demonstrated that CagriSema produces clinically meaningful weight loss — roughly 20% in obesity without diabetes and about 14% in type 2 diabetes — but the headline numbers came in below Novo Nordisk's own guidance and, in a head-to-head trial, fell short of tirzepatide. All the figures below are human randomized controlled trial data, the strongest evidence tier, though the newest readout (REDEFINE 4) is a topline announcement that has not yet been peer-reviewed. The estimand distinction matters: the "trial-product" (adherent) estimand assumes everyone stays on the drug, while the "treatment-policy" (intention-to-treat) estimand reflects real-world adherence and is the lower, more conservative number.
Trial | Population | Design / estimand | Weight loss | Key finding / limitation |
|---|---|---|---|---|
REDEFINE 1 | 3,417 adults, obesity/overweight, no T2D | Phase 3 RCT, 68 wk; treatment-policy (ITT) | −20.4% vs −3.0% placebo (22.7% adherent) | Beat semaglutide alone (16.1%) but missed Novo's ~25% guidance |
REDEFINE 2 | 1,206 adults, obesity + T2D | Phase 3 RCT, 68 wk | −13.7% vs −3.4% placebo (15.7% adherent) | Smaller in T2D (expected); HbA1c ≤6.5% in 73.5% vs 15.9% |
REDEFINE 4 | 809 adults, obesity | Phase 3 open-label, 84 wk, vs tirzepatide 15 mg | 23.0% vs 25.5% (if-all-adhere) | Missed non-inferiority; topline only, not yet peer-reviewed |
Phase 1b (Enebo, 2021) | healthy adults, overweight/obesity | RCT, multiple-ascending dose | Additive vs either agent alone | Established the combination rationale |
REDEFINE 1 — obesity without diabetes
REDEFINE 1 randomized 3,417 adults with obesity or overweight (without type 2 diabetes) to CagriSema, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo once weekly for 68 weeks, and CagriSema produced a mean 20.4% weight loss under the treatment-policy estimand versus 3.0% for placebo — rising to 22.7% among fully adherent participants. Published in the New England Journal of Medicine by Garvey and colleagues, the trial found 40.4% of adherent CagriSema patients lost at least 25% of their body weight. The nuance the news cycle latched onto: 22.7% undershot the roughly 25% Novo Nordisk had guided investors toward, even though it clearly beat the semaglutide-alone arm (16.1% adherent). Strong efficacy, disappointing expectations.
REDEFINE 2 — obesity with type 2 diabetes
REDEFINE 2 tested CagriSema in 1,206 adults with obesity and type 2 diabetes over 68 weeks and produced a mean 13.7% weight loss versus 3.4% for placebo (15.7% among adherent participants). Reported in NEJM by Davies and colleagues, the trial also drove glycemic control, with 73.5% of the CagriSema group reaching an HbA1c of 6.5% or lower versus 15.9% on placebo. The smaller weight-loss figure is expected rather than alarming: patients with type 2 diabetes consistently lose less weight on incretin-based therapies than patients without diabetes, a pattern seen across the GLP-1 class.
REDEFINE 4 — head-to-head against tirzepatide
REDEFINE 4 was the first trial to pit CagriSema directly against tirzepatide, and CagriSema did not meet its primary endpoint of non-inferiority: over 84 weeks in 809 adults with obesity, CagriSema produced 23.0% weight loss versus 25.5% for tirzepatide 15 mg under the if-all-adhere estimand (20.2% vs 23.6% under real-world adherence). Announced by Novo Nordisk in February 2026, this is a topline result that has not yet been peer-reviewed, and the open-label design — participants knew which drug they received — can influence adherence and outcomes. The takeaway is that CagriSema delivers substantial weight loss but, on current data, trails the market-leading dual agonist.
CagriSema for type 2 diabetes — the REIMAGINE program
Beyond obesity, CagriSema is being studied for type 2 diabetes in a separate Phase 3 program called REIMAGINE, where it has shown superior HbA1c reduction and weight loss versus semaglutide across tested doses. The REIMAGINE 2 topline (February 2026) reported HbA1c reductions up to 1.91 percentage points and weight loss up to 14.2%, with 43% of CagriSema 2.4/2.4 mg patients losing at least 15% of body weight. Novo Nordisk has said it will approach regulators about a diabetes pathway after further REIMAGINE and cardiovascular-outcomes data, so the diabetes indication trails the obesity filing.
How does CagriSema compare to tirzepatide, semaglutide, and retatrutide?
On the cleanest available evidence, CagriSema beats semaglutide alone, roughly matches the retatrutide range on cross-trial numbers, and trails tirzepatide in the one head-to-head trial run so far. The rigorous way to read this is to separate within-trial comparisons from cross-trial ones. Within REDEFINE 1, CagriSema (22.7%) outperformed its own semaglutide arm (16.1%) and cagrilintide arm (11.8%) — a true head-to-head. In REDEFINE 4, CagriSema (23.0%) trailed tirzepatide (25.5%) — also head-to-head. Retatrutide's roughly 24% Phase 2 figure comes from a different trial in a different population, so it is context, not a direct comparison.
Compound | Mechanism (receptors) | Peak weight loss (trial, estimand) | Dosing | Regulatory status (as of July 2026) |
|---|---|---|---|---|
CagriSema | Amylin + GLP-1 (cagrilintide + semaglutide) | 22.7% / 68 wk (REDEFINE 1, adherent); 23.0% / 84 wk (REDEFINE 4, if-all-adhere) | 2.4/2.4 mg once-weekly SC | Investigational — FDA review, decision expected late 2026 |
Tirzepatide (Zepbound/Mounjaro) | GIP + GLP-1 dual agonist | 25.5% / 84 wk (REDEFINE 4 comparator, if-all-adhere) | Up to 15 mg once-weekly SC | FDA-approved (obesity + type 2 diabetes) |
Semaglutide (Wegovy/Ozempic) | GLP-1 receptor agonist | 16.1% / 68 wk (REDEFINE 1 comparator, adherent) | 2.4 mg once-weekly SC | FDA-approved (obesity + type 2 diabetes) |
Retatrutide | GLP-1 + GIP + glucagon triple agonist | ~24.2% / 48 wk (Phase 2 — cross-trial, not head-to-head) | Investigational dosing | Investigational (Phase 3) |
The practical read for a buyer: two of these four are approved and available by prescription (tirzepatide and semaglutide), and two are investigational (CagriSema and retatrutide). If you are weighing the two approved GLP-1 options against each other, the semaglutide vs tirzepatide comparison and the tirzepatide dual GIP/GLP-1 mechanism article cover that decision in detail. CagriSema's distinguishing feature is its amylin mechanism, not a higher ceiling than what is already on the market.
What are CagriSema's side effects?
CagriSema's side effects are dominated by gastrointestinal events — nausea, vomiting, diarrhea, constipation, and abdominal pain — most of them mild to moderate and transient, consistent with the GLP-1 receptor agonist class. In REDEFINE 1, gastrointestinal adverse events affected 79.6% of the CagriSema group versus 39.9% on placebo; in REDEFINE 2, the figures were 72.5% versus 34.4%. Because the trials included semaglutide-alone and cagrilintide-alone arms, they showed that CagriSema caused more gastrointestinal events and more treatment discontinuations than semaglutide alone, and more injection-site reactions than semaglutide or placebo. Serious adverse events were also somewhat more common with the combination than with semaglutide alone.
None of this is unique to CagriSema — the GLP-1 and amylin classes share this tolerability profile — but the combination sits at the higher end of gastrointestinal burden precisely because it stacks two appetite-suppressing mechanisms. For a cross-compound view of how these effects compare across the metabolic peptide field, see the peptide side effects overview.
Is CagriSema approved, and can you actually buy it?
No — as of July 2026, CagriSema is not approved anywhere, and there is no legal way to obtain it outside an enrolled clinical trial. Novo Nordisk submitted a New Drug Application to the US FDA on December 18, 2025, based on REDEFINE 1 and REDEFINE 2, with a regulatory decision anticipated in late 2026. No submission to the European Medicines Agency or the UK's MHRA has been publicly confirmed. Because CagriSema is a co-formulated investigational product, it is also not available through compounding pharmacies.
Can you buy "CagriSema"?
You cannot buy CagriSema as a product, because it is a fixed co-formulation that only exists inside Novo Nordisk's clinical supply — no research vendor sells "CagriSema." What research vendors do sell, separately, are its two component compounds: cagrilintide and semaglutide, both offered research-use-only. This is where honesty matters most. Buying two vials and combining them yourself is not the trial drug: it is not the validated fixed-dose formulation, the doses and mixing are not established, and there is zero clinical data on self-combined, separately-sourced product. The REDEFINE results describe a specific manufactured combination, not a do-it-yourself mix. For the prescription-versus-research-market landscape, see can you get semaglutide without a prescription and compounding pharmacy vs research peptide, and for how vendors compare on independent data, the shops directory.
If you're looking at the component compounds, how do you verify quality?
If you are evaluating cagrilintide or semaglutide from the research market, verify HPLC purity of at least 98%, mass-spectrometry identity confirmation, and quantity against the labeled mg — and insist on a third-party certificate of analysis rather than a vendor's in-house numbers. Peptigrity's independent platform tracks 426 shops and publishes 10,051 HPLC purity tests across 69 peptides (verified July 2026); semaglutide alone accounts for 383 of those independent analyses, one of the largest test sets on the platform. That data exists precisely so buyers do not have to take a vendor's word for purity. Combining two compounds doubles the verification burden — both must pass, separately.
Check | What it confirms | How to verify | Red flag |
|---|---|---|---|
HPLC purity ≥98% | Actual peptide content vs impurities | Third-party HPLC certificate from a named lab | No CoA, or a vendor-run "in-house" test only |
Mass-spec identity | The vial holds the right molecule | MS confirming the expected mass (semaglutide ≈4114 Da; cagrilintide is a separate, larger acylated peptide) | Purity reported but no identity/MS data |
Quantity / net content | Labeled mg matches actual peptide mass | Independent quantity test compared to the label | A "10 mg" claim with no quantity verification |
Independent data on Peptigrity | Cross-checks the vendor's own claims | Look the compound up in the lab-tests database | Vendor cites only its own numbers |
Two-compound DIY burden | Both compounds pass, independently | Verify cagrilintide and semaglutide separately | Treating a self-mix as equal to the trial drug |
Third-party testing removes the conflict of interest baked into vendor-provided certificates, because the lab has no stake in the result. To act on this, browse independent results in the peptide lab-tests database, learn the workflow in how to test peptides, read a certificate correctly with how to read peptide lab test results: HPLC and mass spec explained, and check sourcing specifics in where to buy semaglutide: 7 purity and identity checks. If you are calculating doses for the semaglutide component, the semaglutide dosing calculator handles the reconstitution math.
Frequently Asked Questions
Is CagriSema better than tirzepatide?
On the only head-to-head trial run so far, CagriSema did not outperform tirzepatide. REDEFINE 4 showed 23.0% weight loss for CagriSema versus 25.5% for tirzepatide 15 mg (if-all-adhere), missing its non-inferiority endpoint. CagriSema's advantage is its distinct amylin mechanism, not a higher weight-loss ceiling than the approved market leader.
Can I make my own CagriSema by combining cagrilintide and semaglutide?
There is no evidence supporting a self-combined version, and it is not the same as the trial drug. CagriSema is a validated fixed-dose co-formulation studied under specific conditions; combining two separately-sourced research vials has no clinical data, no established dosing, and no safety validation. Peptigrity does not provide DIY co-administration protocols. If you are researching the component compounds, verify each one's purity and identity independently.
When will CagriSema be FDA approved?
As of July 2026, CagriSema is under FDA review, with a decision expected in late 2026. Novo Nordisk filed its application in December 2025 based on REDEFINE 1 and REDEFINE 2. No approval date is confirmed, and regulatory timelines can shift — verify the current status before relying on any date.
How much weight can you lose on CagriSema?
In REDEFINE 1, adults with obesity and no diabetes lost a mean of 20.4% under real-world adherence and 22.7% among fully adherent participants over 68 weeks. In type 2 diabetes (REDEFINE 2), the figures were 13.7% and 15.7%. Individual results vary, and these are trial averages, not guarantees.
Does CagriSema work for type 2 diabetes?
Yes — in REDEFINE 2 and the REIMAGINE program, CagriSema produced meaningful weight loss and strong glycemic control in type 2 diabetes, with 73.5% of REDEFINE 2 patients reaching an HbA1c of 6.5% or lower. The weight-loss figure is lower in diabetes than in obesity without diabetes, which is expected for the incretin class. A formal diabetes filing trails the obesity application.
This article is for educational and informational purposes only and does not constitute medical advice. Peptides discussed may be investigational compounds not approved by the FDA (or equivalent regulators in your jurisdiction) for human use. Always consult a qualified healthcare provider before using any peptide or research compound. Peptigrity is an independent review platform and does not sell, endorse, or recommend specific products or vendors.
