CagriSema and Novo Nordisk's obesity pipeline: what is public

Key points

• CagriSema is a fixed-dose, once-weekly injection of cagrilintide (an amylin analogue) plus semaglutide. Novo Nordisk submitted it to the US FDA on 18 December 2025. As of Novo’s 4 November 2026 report we found no approval [1][3].
• In REDEFINE 1 (3,417 adults without diabetes, 68 weeks, Novo-funded), mean weight change was -20.4 percent with CagriSema and -3.0 percent with placebo [4].
• In REDEFINE 4, an open-label head-to-head, CagriSema did not show non-inferiority to tirzepatide 15 mg: 23.0 against 25.5 percent in the adherent analysis [2].
• Cagrilintide alone is investigational. Research-use-only vials are not the trial product.

What cagrilintide is

Novo describes cagrilintide as “a long-acting amylin analogue” [3]. In the trials it is given by weekly subcutaneous injection [3]. Semaglutide, the partner in CagriSema, is a GLP-1 receptor agonist [3]. Our overview of Novo’s business is at Novo Nordisk (NVO) GLP-1 business.

Cagrilintide’s first large human result alone came from a phase 2 dose-finding trial published in The Lancet in November 2021. It randomised 706 adults with obesity, or with overweight plus hypertension or dyslipidaemia, across 57 sites in 10 countries for 26 weeks. At the highest of five weekly doses (4.5 mg), weight fell 10.8 percent, against 9.0 percent with daily liraglutide 3.0 mg and 3.0 percent with placebo. Gastrointestinal events occurred in 41 to 63 percent of cagrilintide groups against 32 percent with placebo. The trial was funded by Novo Nordisk, with grants from the Novo Nordisk Foundation and the UK NIHR [7].

Regulatory status

• United States, as of Novo’s 4 November 2026 report: CagriSema is not approved. The new drug application sought weight reduction and long-term maintenance in adults with obesity, or overweight plus a weight-related condition [3]. In February 2026 Novo said a decision was anticipated by late 2026 [2]. The CEO’s quote in the 4 November report is that Novo is “preparing for the US launch of CagriSema in early 2027, subject to regulatory approval” [1]. We found no public decision date and no approval announcement.
• EU: Novo’s December 2025 release stated CagriSema was not approved in the US or the EU [3]. We did not check the EMA register.
• UK, Germany: not checked.
• Cagrilintide alone: no marketing authorisation that we found; Novo calls it investigational. “Research use only” means a supplier labels a product as not for human or veterinary use; such products have no regulatory review of identity, purity or dose and are not the formulation tested in Novo’s trials. We compare cagrilintide as a research peptide on the cagrilintide page.

The REDEFINE programme

All trials below are sponsored by Novo Nordisk. Results marked “sponsor-reported” come from company releases, not peer-reviewed papers.

Trial	Population	Size	Duration	Comparator	Status
REDEFINE 1	Obesity or overweight, no diabetes	3,417	68 weeks	Placebo, semaglutide alone, cagrilintide alone	Published in NEJM [4]
REDEFINE 2	Obesity or overweight with type 2 diabetes	1,206	68 weeks	Placebo	Published in NEJM [5]
REDEFINE 3	Established cardiovascular disease	about 7,000	event-driven	Placebo	Ongoing [2]
REDEFINE 4	Obesity with at least one comorbidity	809	84 weeks	Tirzepatide 15 mg, open-label	Sponsor-reported [2]
REDEFINE 8	Obesity, body composition	400	104 weeks plus 52-week extension	Placebo	Described in Novo’s release [2]
REDEFINE 9	Overweight or obesity	300	68 weeks	Placebo	Sponsor-reported [1][2]
REDEFINE 11	Obesity	600	80 weeks plus extension	Placebo	Data expected H1 2027 per Novo [2]

REDEFINE 1 and 2

REDEFINE 1 randomised 3,417 adults 21:3:3:7 to CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg, n=2,108), semaglutide (302), cagrilintide (302) or placebo (705), all with lifestyle intervention. Mean weight change at week 68 was -20.4 percent with CagriSema against -3.0 percent with placebo, a difference of 17.3 percentage points. Gastrointestinal events occurred in 79.6 percent of the CagriSema group and 39.9 percent of the placebo group [4]. Novo’s own “trial product” analysis, which assumes everyone stayed on treatment, gave 22.7 against 2.3 percent [3]. These are two different calculations of the same trial, not conflicting results.

The REDEFINE 1 record says it is funded by Novo Nordisk and lists the registry number NCT05567796 [4]. ClinicalTrials.gov lists Novo Nordisk as sponsor, with study completion estimated for October 2026 [6]. We could not open the paper’s figures for the semaglutide-alone arm, so we do not report that result.

REDEFINE 2 randomised 1,206 adults with type 2 diabetes and a BMI of 27 or more, 3:1, to CagriSema or placebo (904 and 302) in 12 countries. Weight changed by -13.7 percent against -3.4 percent. HbA1c of 6.5 percent or lower was reached by 73.5 percent against 15.9 percent. Gastrointestinal events were 72.5 percent against 34.4 percent. It was also funded by Novo Nordisk [5].

Novo reported discontinuation because of adverse events of 5.9 percent against 3.5 percent in REDEFINE 1 and 8.4 percent against 3 percent in REDEFINE 2 [3].

Cagrilintide alone in REDEFINE 1

At the EASD congress in September 2025 Novo presented cagrilintide-alone data from REDEFINE 1: 11.8 percent weight loss against 2.3 percent with placebo at 68 weeks, as reported by BioSpace from Novo’s release. The estimand was not stated in that article. Novo said it would run a dedicated phase 3 programme, RENEW, planned to start in the fourth quarter of 2025 [8]. We did not find a RENEW readout.

REDEFINE 4 against tirzepatide

REDEFINE 4 is the only trial we found where the company directly compares CagriSema with tirzepatide. In 809 adults over 84 weeks, open-label, the adherent-population estimand showed 23.0 percent weight loss with CagriSema against 25.5 percent with tirzepatide 15 mg. The estimand that ignores adherence showed 20.2 against 23.6 percent. The trial missed its non-inferiority primary endpoint [2]. Novo called CagriSema “safe and well-tolerated” but gave no adverse event rates in that release [2].

REIMAGINE 5

In adults with type 2 diabetes, Novo reports 12.4 percent weight loss with CagriSema against 9.1 percent with tirzepatide 5 mg at week 60, with HbA1c reduction judged non-inferior [1]. It does not give the trial size in the report we read.

Comparing across trials

Different trials enrolled different people, ran for different lengths and used different estimands. The -20.4 percent in REDEFINE 1 (68 weeks, placebo-controlled, no diabetes) cannot be set against a tirzepatide figure from another trial, and the numbers in the table above should not be ranked against one another. The two like-for-like comparisons with tirzepatide are REDEFINE 4 and REIMAGINE 5, both sponsor-reported, and both used a single tirzepatide dose. We did not compare CagriSema with semaglutide alone beyond noting that REDEFINE 1 included such an arm.

Other late-stage assets

Novo’s 4 November report says the oral GLP-1 and amylin agonist zenagamtide, which Novo’s own release says is also known as amycretin, has entered the AMAZE phase 3 programme: “AMAZE 9 phase 3 trial with oral zenagamtide has been initiated in September.” A phase 3 diabetes trial, AMBITION 7, was also started. The report also lists an oral amylin candidate, “355”, in a phase 2 trial [1].

In a 6 June 2026 release, Novo gave phase 2 data for subcutaneous zenagamtide in type 2 diabetes: 262 adults, 36 weeks, six doses against placebo. Weight fell by up to 14.6 percent at the 40 mg dose against 2.10 percent with placebo. The data were from a poster, not a peer-reviewed paper, and only 37 participants were on placebo [9]. Novo also announced a planned high-dose CagriSema (2.4 mg/7.2 mg) phase 3 trial for the second half of 2026 [2]. We did not open registry records for these assets and do not cover other Novo candidates.

Risks and unknowns

• Documented adverse effects. In REDEFINE 1, nausea was 55 percent against 12.6 percent with placebo, constipation 30.7 against 11.6 percent and vomiting 26.1 against 4.1 percent, per Novo’s release (a BioSpace copy was our source for these rates) [3]. Most gastrointestinal events were reported as mild to moderate and transient [4][5].
• Not established. Long-term safety beyond 68 to 84 weeks, effects on cardiovascular events (REDEFINE 3 is ongoing), and outcomes in children or pregnancy are not reported in the sources we read. Interaction data were not covered.
• Labels. We did not open any CagriSema label (none exists yet) and did not check which warnings it would carry.
• Unverified. The FDA decision date; EMA, MHRA and BfArM status; the semaglutide-alone and cagrilintide-alone REDEFINE 1 results from the paper; the RENEW start; REIMAGINE 5 size.
• Cagrilintide alone has not been approved. Its tolerability outside trial supply and dosing is undocumented here.

Frequently asked questions

What is CagriSema? It is a once-weekly injection combining cagrilintide 2.4 mg, an amylin analogue, with semaglutide 2.4 mg, a GLP-1 receptor agonist. Novo submitted it to the FDA in December 2025 [3].

Is CagriSema approved? Not in the sources we read. Novo’s 4 November 2026 report says it is preparing for a US launch in early 2027, subject to approval [1].

Did CagriSema beat tirzepatide? No, in the REDEFINE 4 trial reported by Novo. It missed its non-inferiority endpoint: 23.0 against 25.5 percent weight loss in the adherent analysis [2]. In REIMAGINE 5 (type 2 diabetes), Novo reported more weight loss against tirzepatide 5 mg [1].

Is cagrilintide the same as a research-use-only vial? No. The trial product is Novo’s manufactured formulation given under study protocols. A research-use-only product carries no such assurance and no approved use.

Sources

1. Novo Nordisk A/S, Form 6-K, Company Announcement No 65/2026, “Financial report for the period 1 January 2026 to 30 September 2026” (2026-11-04). https://www.sec.gov/Archives/edgar/data/353278/000162828026069805/caq32026.htm
2. Novo Nordisk A/S, Form 6-K, REDEFINE 4 headline results (2026-02-23). https://www.sec.gov/Archives/edgar/data/353278/000117184326000996/f6k_022326.htm
3. Novo Nordisk, “Novo Nordisk files for FDA approval of CagriSema” (2025-12-18); rates also read in the BioSpace copy (2025-12-19). https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?embed=true&id=916470 and https://www.biospace.com/press-releases/novo-nordisk-files-for-fda-approval-of-cagrisema-the-first-once-weekly-combination-of-glp-1-and-amylin-analogues-for-weight-management
4. Garvey WT et al., “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity”, N Engl J Med 393(7):635-647 (online 2025-06-22), PMID 40544433, read through the Europe PMC record. https://pubmed.ncbi.nlm.nih.gov/40544433/
5. Davies MJ et al., “Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes”, N Engl J Med 393(7):648-659 (online 2025-06-22), PMID 40544432, read through the Europe PMC record. https://pubmed.ncbi.nlm.nih.gov/40544432/
6. ClinicalTrials.gov, NCT05567796 (REDEFINE 1), API record read 2026-11-08. https://clinicaltrials.gov/study/NCT05567796
7. Lau DCW et al., “Once-weekly cagrilintide for weight management in people with overweight and obesity”, Lancet 398(10317):2160-2172 (2021-11-16), PMID 34798060, read through the Europe PMC record. https://pubmed.ncbi.nlm.nih.gov/34798060/
8. BioSpace, “Novo’s Amylin Injectable Cagrilintide Hits 11.8% Weight Reduction in Phase III Trial” (2025-09-16). https://www.biospace.com/drug-development/novos-amylin-injectable-cagrilintide-hits-11-8-weight-reduction-in-phase-iii-trial
9. Novo Nordisk, “Novo Nordisk’s investigational zenagamtide shows HbA1C reductions and up to 14.6% weight loss in adults with type 2 diabetes, presented at ADA 2026” (2026-06-06). https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916559

This article is information, not medical advice.

This is not investment advice.