Is CagriSema FDA-approved?

No. As of August 26, 2026 CagriSema is not approved in the United States. It has no entry in FDA's Drugs@FDA database, no label on DailyMed, and does not appear on FDA's list of 2026 novel drug approvals. Novo Nordisk submitted a New Drug Application for weight management on December 18, 2025 and states in that release that CagriSema is not approved in the US or EU. The company's August 4, 2026 half-year report lists a US decision among expected fourth-quarter 2026 milestones. Neither FDA nor the company has published a PDUFA date.

What is CagriSema and how is it different from a GLP-1 alone?

CagriSema is an investigational fixed-dose combination of semaglutide 2.4 mg, a GLP-1 receptor agonist, and cagrilintide 2.4 mg, a long-acting analogue of amylin. Amylin is a pancreatic hormone that induces satiety, and cagrilintide acts on appetite regulation through direct effects in the brain, so the combination targets two appetite pathways rather than one. An amylin analogue is already approved in the US — pramlintide (SymlinPen) — but only for glucose control in people with diabetes who use mealtime insulin, and it is dosed three times a day rather than once a week.

What did REDEFINE 1 and REDEFINE 2 actually show?

REDEFINE 1 randomised 3,417 adults without diabetes for 68 weeks. Under the treatment-policy estimand, which counts everyone randomised whether or not they stayed on treatment, mean body weight changed by -20.4% with cagrilintide-semaglutide versus -3.0% with placebo, a difference of 17.3 percentage points (95% CI -18.1 to -16.6). REDEFINE 2 randomised 1,206 adults with type 2 diabetes for 68 weeks; the same estimand gave -13.7% versus -3.4%, a difference of 10.4 percentage points (95% CI -11.2 to -9.5). Figures of 22.7% and 15.7% circulating in secondary coverage are the same trials analysed under the trial-product estimand, which the sponsor defines as estimated efficacy in an idealised scenario in which all patients stayed on treatment. They are not the published primary results and must not be compared with treatment-policy figures from other drugs.

Is CagriSema better than Zepbound (tirzepatide)?

A randomised head-to-head exists and it did not favour CagriSema. REDEFINE 4 (NCT06131437) compared CagriSema 2.4/2.4 mg with tirzepatide 15 mg in 809 adults with obesity over 84 weeks, open-label. On February 23, 2026 Novo Nordisk announced that the trial did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared with tirzepatide. The reported figures were 23.0% versus 25.5% if all people adhered to treatment, and 20.2% versus 23.6% under the treatment-regimen estimand. A failed non-inferiority test means the trial could not rule out that CagriSema is worse than tirzepatide by more than the pre-set margin; it is not a superiority test, and no source states that tirzepatide was shown to be statistically superior. These are topline company figures; there is no peer-reviewed publication and no posted registry results, so no confidence intervals or independent review are available.

How well tolerated was CagriSema in the trials?

Gastrointestinal adverse events affected 79.6% of the CagriSema group versus 39.9% on placebo in REDEFINE 1, and 72.5% versus 34.4% in REDEFINE 2, described in both publications as mainly transient and mild to moderate. Novo Nordisk reports adverse events leading to discontinuation in 5.9% of the CagriSema group versus 3.5% on placebo in REDEFINE 1, and 8.4% versus 3% in REDEFINE 2. Because REDEFINE 1 included monotherapy arms, a within-trial comparison is possible: withdrawal for adverse events occurred in 5.9% on CagriSema, 3.6% on semaglutide alone, 2.6% on cagrilintide alone and 3.5% on placebo, with serious adverse events in 9.8%, 5.0%, 8.9% and 6.1% respectively, and two fatal adverse events in the CagriSema arm (2 of 2,106 participants, 0.1%, with none in the other three arms), listed as a malignancy and a suicide and not attributed to the drug.

Weight & Metabolic Health

CagriSema: what the REDEFINE trials showed, and what an FDA decision would change

By the US Health Digest editorial team · Published August 26, 2026 · Every claim linked to its primary source

CagriSema is not an approved medicine. As of August 26, 2026 it cannot be prescribed, dispensed or priced in the United States: it has no entry in FDA's Drugs@FDA database, no label on DailyMed, and it does not appear on FDA's list of 2026 novel drug approvals. Novo Nordisk's own December 18, 2025 release says plainly: "CagriSema is not approved in the US or EU." That release announced a New Drug Application for weight management, based on REDEFINE 1 and REDEFINE 2. The company's August 4, 2026 half-year report lists a "CagriSema — US decision" among expected fourth-quarter 2026 milestones. Neither FDA nor the company has published a PDUFA date; we searched and found none.

What CagriSema is, and why the combination is a different idea

CagriSema is a fixed-dose combination of two once-weekly injected peptides: semaglutide 2.4 mg, the GLP-1 receptor agonist already sold as Wegovy, and cagrilintide 2.4 mg, which is not approved in the United States in any form — FDA’s own drug databases return no record of it. Cagrilintide is an amylin analogue. Amylin is a pancreatic hormone co-secreted with insulin; the phase 2 dose-finding trial describes it as a "pancreatic hormone that induces satiety", with cagrilintide engineered as a long-acting analogue of it. The chemistry paper from the team that built the molecule explains why it took so long: a hallmark of amylin, the authors write, is "its high propensity toward the formation of amyloid fibrils, which makes it a challenging drug design effort."

So the rationale is two appetite pathways rather than one. A secondary analysis of REDEFINE 1 published in Hypertension puts it this way: cagrilintide "impacts appetite regulation through direct effects in the brain," and, in the authors’ words, "combining therapies with complementary but distinct mechanisms of action may lead to greater weight loss and improvements in associated risk factors compared with individual medications."

An amylin analogue is in fact already FDA-approved here. Pramlintide (SymlinPen) is indicated "for patients with type 1 or type 2 diabetes who use mealtime insulin and have failed to achieve desired glycemic control despite optimal insulin therapy" — glucose control, not weight management, and dosed before each major meal rather than once a week. Approval is not the same as availability, though: FDA’s Drugs@FDA record for pramlintide (NDA 021332) currently lists every SYMLIN presentation as discontinued. The class is not new; the weekly version, and its use for weight, would be.

Where the application actually stands

Nov 2022 – Mar 2023: REDEFINE 1, 2 and 3 begin (NCT05567796, NCT05394519, NCT05669755).
Dec 20, 2024: REDEFINE 1 topline announced.
Mar 10, 2025: REDEFINE 2 topline announced; company then expected to file in Q1 2026.
Jun 22, 2025: both trials published in the New England Journal of Medicine (PMID 40544433, PMID 40544432).
Dec 18, 2025: NDA submitted to FDA for weight management, "to be used with a reduced-calorie diet and increased physical activity."
Feb 23, 2026: REDEFINE 4, the head-to-head against tirzepatide, misses its primary endpoint.
Aug 4, 2026: half-year report lists a US decision among Q4 2026 milestones.
Sep 2027: earliest scheduled primary completion of the cardiovascular outcomes trial.

The trials, with each result tied to its estimand

The registered REDEFINE phase 3 trials relevant to a US weight-management decision, as of August 26, 2026. CagriSema is not approved; no trial in this table has results posted on ClinicalTrials.gov. The result column carries only *treatment-policy* estimand figures from the peer-reviewed publications — the analysis that counts everyone randomised, whether or not they stayed on the drug. REDEFINE 4's numbers are deliberately excluded from this column because its topline release reports different estimands; they appear in the text below instead.
Trial	NCT	Population	n	Duration	Primary endpoint	Result (treatment-policy estimand)	Source
REDEFINE 1	NCT05567796	Adults without diabetes, BMI ≥30 or ≥27 with a complication	3,417	68 weeks	Co-primary: relative change in body weight; ≥5% reduction	−20.4% vs −3.0% placebo (difference −17.3 points, 95% CI −18.1 to −16.6; P<0.001)	NEJM 2025;393:635-647
REDEFINE 2	NCT05394519	Adults with type 2 diabetes, BMI ≥27, HbA1c 7–10%	1,206	68 weeks	Co-primary: percent change in body weight; ≥5% reduction	−13.7% vs −3.4% placebo (difference −10.4 points, 95% CI −11.2 to −9.5; P<0.001)	NEJM 2025;393:648-659
REDEFINE 4	NCT06131437	Adults with obesity and one or more comorbidities; open-label	809	84 weeks	Non-inferiority vs tirzepatide 15 mg on relative weight change	Primary endpoint not met. No peer-reviewed publication exists; company topline only	Company announcement, Feb 23, 2026
REDEFINE 3	NCT05669755	Adults with established cardiovascular disease	7,101	Event-driven; primary completion Sep 2027	Time to first 3-point major adverse cardiovascular event	No results. Ongoing	Registry record

Two details about REDEFINE 1 that matter to this site's readers, from the open-access Hypertension analysis of the same trial: participants were 67.6% female, mean age 47.0 years, 72.0% White, mean BMI 37.9 — and the authors list that among the study’s weaknesses, not its strengths: "Limitations include a predominantly female and White population."

Why you will see two different numbers for the same trial

Secondary coverage of CagriSema circulates figures of roughly 23%, 22.7% and 15.7%. None of those is a published primary result, and none is wrong either — they are a different analysis of the same data. Novo Nordisk's releases define the two side by side: the trial product estimand is "estimated efficacy in an idealized scenario in which all patients stayed on treatment and took no other weight loss therapies," while the treatment policy estimand is "estimated efficacy regardless of whether patients stayed on treatment or took other weight loss therapies." The published NEJM papers report the treatment-policy analysis as primary in both trials.

So for REDEFINE 1: −20.4% is the published primary; 22.7% is the idealised version of the same result. For REDEFINE 2: −13.7% is the published primary; 15.7% is the idealised version. Any table that puts one drug's idealised figure beside another drug's real-world figure is comparing two different questions. On a related mix-up, see our note on how oral GLP-1 trials get compared.

Within one trial and one estimand, the comparison is legitimate. Under the trial-product estimand, REDEFINE 1 reported 22.7% for CagriSema, 16.1% for semaglutide 2.4 mg alone, 11.8% for cagrilintide 2.4 mg alone and 2.3% for placebo; the peer-reviewed Hypertension paper reports the same ordering, with 61.5% of the CagriSema group reaching at least 20% weight loss versus 29.5% on semaglutide and 15.2% on cagrilintide — responder proportions that the paper reports without attaching an estimand label, though its analyses of this kind draw on the on-treatment period, which is the trial-product basis. Under the treatment-policy estimand, the company reports that 91.9% of the CagriSema group reached at least 5% weight reduction, against 31.5% on placebo. That within-trial ordering is the basis for the claim that the amylin component adds something to semaglutide. One caveat on what was formally tested: the published abstract reports the primary comparison as CagriSema versus placebo, and because the full text is paywalled to us we cannot say how the comparison against semaglutide monotherapy was analysed.

"Is it better than Zepbound?" There is a head-to-head, and it did not go the way the sponsor hoped

Cross-trial comparison is not evidence. Different trials enrol different people, run different lengths, and analyse under different estimands, so lining up a number from one against a number from another tells you very little. The only thing that settles it is a randomised head-to-head — and for once, one exists.

REDEFINE 4 randomised 809 adults with obesity to CagriSema 2.4/2.4 mg or tirzepatide 15 mg for 84 weeks, open-label. On February 23, 2026 Novo Nordisk announced that "the trial did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared to tirzepatide after 84 weeks." The reported figures, in the release's own words: "if all people adhered to treatment," 23.0% for CagriSema versus 25.5% for tirzepatide; "when applying the treatment-regimen estimand," 20.2% versus 23.6%. Both estimands favour tirzepatide numerically. What a failed non-inferiority test does and does not show matters here: it means the trial could not rule out that CagriSema is worse than tirzepatide by more than the pre-set margin. It is not a superiority test, and neither the company release nor any published report states that tirzepatide was tested as, or shown to be, statistically superior. These are topline company figures. There is no peer-reviewed publication of REDEFINE 4, no posted registry results, and therefore no confidence intervals, no baseline table and no independent peer review of any of it.

In the same release the company's chief scientific officer described "clinically meaningful additive weight loss effects superior to what has been observed with GLP-1 biology alone." That is a company characterisation of the comparison against semaglutide, not against tirzepatide, and it sits in the same document as the missed endpoint. Both belong in the reader's head at once.

It is worth seeing how badly indirect comparison performed here. A 2026 network meta-analysis of 25 trials placed tirzepatide 15 mg and CagriSema essentially level on percent weight reduction — mean differences versus placebo of −17.97% (95% CI −19.72 to −16.21) for tirzepatide 15 mg and −17.46% (95% CI −20.55 to −14.37) for cagrilintide 2.4 mg plus semaglutide 2.4 mg — and ranked CagriSema first at the 20% threshold (relative risk 27.82 versus 23.70). The −17.84% figure in that paper’s abstract belongs to a different, higher-dose combination — cagrilintide 4.5 mg plus semaglutide 2.4 mg — not to the product under FDA review. The direct trial pointed the other way. Indirect rankings are a hypothesis; a head-to-head is a test. For the approved drugs, see Wegovy vs Zepbound and the higher-dose semaglutide approval.

Tolerability, reported honestly

This is the live question with an amylin-plus-GLP-1 combination, and the published abstracts are blunt. In REDEFINE 1, gastrointestinal adverse events affected 79.6% of the CagriSema group and 39.9% of the placebo group, described as "mainly transient and mild-to-moderate in severity." In REDEFINE 2 the figures were 72.5% versus 34.4%.

Discontinuation is the number that matters more. Novo Nordisk reports that adverse events led to discontinuation in 5.9% of the CagriSema group versus 3.5% on placebo in REDEFINE 1, and 8.4% versus 3% in REDEFINE 2. The company's EASD 2025 presentation of REDEFINE 1 gives the full four-arm table: adverse events leading to drug withdrawal in 5.9% on CagriSema, 3.6% on semaglutide alone, 2.6% on cagrilintide alone and 3.5% on placebo; serious adverse events in 9.8%, 5.0%, 8.9% and 6.1%; and two fatal adverse events in the CagriSema arm — 2 of 2,106 participants, 0.1%, with none recorded in the other three arms — listed in the deck as a malignancy ("cancer of unknown primary source") and a suicide. The deck does not attribute either death to the drug, and neither do we. Because all four arms sat inside one trial, that is a fair comparison — and it shows the combination was left by more participants than either component alone. Adding a mechanism adds tolerability burden. Our GLP-1 FAQ covers what side effects look like on the approved drugs.

What would change for patients if it were approved — and what would not

An approval would create a label, not a prescription. It would define the indicated population, the dosing schedule, the warnings and the contraindications — and only then would anything else follow.

What cannot be known in advance, and what we will not guess at: a US list price, a net price, a formulary tier, a copay, whether any given insurer or employer would cover it, or when supply would reach pharmacies. None of that exists before an approval, and after one it is a commercial decision, not a scientific finding. Anyone publishing a price for CagriSema today is making it up.

The existing landscape does suggest that approval and access are different events. In KFF's 2025 employer survey, 19% of firms with 200 or more workers covered GLP-1 drugs for weight loss, 16% to 43% by employer size, a third of them with lifestyle-programme requirements. In Medicare and Medicaid, weight-loss drugs sit outside standard Part D coverage; KFF's summary of the Balance model and its bridge arrangement shows how narrow and time-limited those routes are. A new combination product would enter that landscape, not a different one — more numbers in our 2026 GLP-1 statistics.

Two things an approval would not settle. It would not deliver cardiovascular outcome evidence: REDEFINE 3, the trial testing whether CagriSema reduces heart attacks, strokes and cardiovascular death, is not scheduled to reach primary completion until September 2027. And it would not resolve where CagriSema sits against tirzepatide, because the one trial that asked did not meet its endpoint. On the wider pipeline, see retatrutide.

Questions for your prescriber

This is evidence reporting, not medical advice, and nothing here is a reason to start, stop or change a medication.

CagriSema is not approved. What are my options among drugs that are approved today?
If a new combination is approved later, what would make me a candidate — or not?
I have had gastrointestinal side effects on a GLP-1. Does a two-mechanism combination make that more likely for me?
The published trials ran 68 weeks. What is the plan beyond that horizon?
If cardiovascular risk is the reason I want treatment, which drugs have outcome data now?
Trial participants were mostly women in their forties with a BMI near 38. How close is that to me?
If a new drug is approved, how long would coverage under my plan realistically take?

Absence claims and how we tested them

Several statements above assert that something does not exist. Each is scoped to what we searched on August 26, 2026. One: CagriSema is not approved in the US — FDA's own openFDA interface returned no match for "cagrilintide" or "cagrisema" in either the Drugs@FDA or the drug-label endpoint; DailyMed's API returned zero records for both terms against a database published August 25, 2026; and neither term appears on FDA's 2026 novel approvals page, whose most recent entry was dated August 19, 2026. Novo Nordisk states the same in its own release. Two: no PDUFA date is public — the December 18, 2025 release says only that "the FDA is expected to review the CagriSema application in 2026," the February 23, 2026 release says a decision "is anticipated by late 2026," and the August 4, 2026 half-year report lists a US decision as a Q4 2026 milestone without a date. FDA does not publish review clocks for pending applications. Three: no FDA advisory committee meeting on CagriSema is listed on the Endocrinologic and Metabolic Drugs Advisory Committee page. Four: REDEFINE 4 has no peer-reviewed publication — PubMed searches for "NCT06131437" returned zero records, and neither "cagrisema AND tirzepatide" (24 records) nor "REDEFINE AND cagrisema" (11 records) contained the trial report. Five: none of the four trials above has results posted on ClinicalTrials.gov. One limitation we will state rather than hide: the two NEJM papers are paywalled to us. Every REDEFINE 1 and 2 figure here comes from the PubMed abstract, the open-access Hypertension secondary analysis, the registry, or Novo Nordisk's own releases and congress presentation — each labelled as such. We have not read the full texts or supplements.

Sources

Novo Nordisk. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management. Plainsboro, NJ and Bagsværd, December 18, 2025. Contains the estimand definitions, the discontinuation figures, and the statement "CagriSema is not approved in the US or EU."
Novo Nordisk. CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved. Company announcement, Bagsværd, February 23, 2026.
Novo Nordisk. CagriSema demonstrates superior weight loss in adults with obesity or overweight in the REDEFINE 1 trial. December 20, 2024 — the four-arm trial-product and treatment-policy figures.
Novo Nordisk. CagriSema demonstrates superior weight loss in adults with obesity or overweight and type 2 diabetes in the REDEFINE 2 trial. March 10, 2025.
Novo Nordisk A/S. Financial report for the first six months of 2026, filed with the SEC on Form 6-K, August 4, 2026. Expected regulatory milestones.
Garvey WT, Blüher M, Osorto Contreras CK, et al.; REDEFINE 1 Study Group. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2025;393(7):635-647. PubMed 40544433. Registry record: NCT05567796.
Davies MJ, Bajaj HS, Broholm C, et al.; REDEFINE 2 Study Group. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. New England Journal of Medicine. 2025;393(7):648-659. PubMed 40544432. Registry record: NCT05394519.
Verma S, Böttcher M, Brown P, et al. CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. Hypertension. 2026;83(2):e26055. Open-access full text (PubMed Central); PubMed 41328546.
ClinicalTrials.gov registry records: NCT06131437 (REDEFINE 4, CagriSema vs tirzepatide 15 mg, completed) and NCT05669755 (REDEFINE 3, cardiovascular outcomes, ongoing). National Library of Medicine.
Garvey WT, et al. REDEFINE 1 presentation, EASD 2025 (Novo Nordisk Science Hub). Four-arm adverse-event overview and categorical weight-loss slides.
Lau DCW, Erichsen L, Francisco AM, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial. Lancet. 2021;398(10317):2160-2172. PubMed 34798060.
Kruse T, Hansen JL, Dahl K, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of Medicinal Chemistry. 2021;64(15):11183-11194. PubMed 34288673.
DailyMed. SYMLINPEN (pramlintide acetate) injection — current prescribing information. National Library of Medicine.
Comparative Effectiveness of CagriSema, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials. Endocrinology, Diabetes & Metabolism. 2026;9(4):e70248. Open-access full text (PubMed Central).
U.S. Food and Drug Administration. Novel Drug Approvals for 2026.
KFF. 2025 Employer Health Benefits Survey, and What to Know About the Balance Model for GLP-1s in Medicare and Medicaid.

This article is for information only and is not medical advice. Prescription weight-loss medication requires evaluation by a licensed clinician. See our medical disclaimer.