CagriSema and Amycretin: Novo Nordisk Obesity Pipeline

CagriSema is Novo Nordisk’s once-weekly injection that combines cagrilintide, an amylin analog, with semaglutide, the GLP-1 drug in Wegovy and Ozempic. Amycretin, which Novo’s recent releases call zenagamtide (formerly amycretin), is a single molecule that targets the same two pathways. Together they are the core of Novo’s effort to follow Wegovy in obesity, and as of November 4, 2026 CagriSema is awaiting an FDA decision.

Mechanism at a glance

CagriSema pairs two separate drugs in one fixed-dose injection: semaglutide activates the GLP-1 receptor, and cagrilintide mimics amylin, a hormone involved in appetite. Zenagamtide (amycretin) is described by Novo as a unimolecular GLP-1 and amylin receptor agonist, being studied in both injectable and oral forms.

Why it matters

Novo announced on December 18, 2025 that it had submitted a New Drug Application for CagriSema (cagrilintide 2.4 mg and semaglutide 2.4 mg) for weight reduction and long-term weight maintenance in adults with obesity or overweight and at least one weight-related condition. The filing rests on two Phase 3 trials. In REDEFINE 1 (3,417 adults without diabetes, 68 weeks), Novo reported mean weight loss of 22.7% vs 2.3% on placebo if all participants stayed on treatment, and 20.4% vs 3.0% regardless of adherence. In REDEFINE 2 (1,206 adults with type 2 diabetes), it was 15.7% vs 3.1% and 13.7% vs 3.4%. Both were published in the New England Journal of Medicine in June 2025.

Novo’s own materials do not give a specific FDA action date. The company said in February 2026 that it expects a decision in late 2026, and its August 2026 half-year report lists a CagriSema US decision among expected 2026 milestones. We found no report of an FDA decision as of November 4, 2026.

Competitive pressure points

• Head-to-head with tirzepatide: in REDEFINE 4 (809 adults, 84 weeks, open label), CagriSema produced 23.0% weight loss vs 25.5% for tirzepatide 15 mg among adherent patients (20.2% vs 23.6% regardless of adherence). Novo reported that the trial did not show non-inferiority. In the type 2 diabetes trial REIMAGINE 4, CagriSema was non-inferior to tirzepatide for weight but not for HbA1c.
• Tolerability: in REDEFINE 1, Novo reported discontinuation due to adverse events of 5.9% vs 3.5% for placebo, and gastrointestinal events in 79.6% vs 39.9% (nausea 55% vs 12.6%, vomiting 26.1% vs 4.1%). In REDEFINE 2, discontinuation was 8.4% vs 3%.
• Lilly’s pipeline: tirzepatide (Zepbound) was approved by the FDA for chronic weight management in November 2023; Lilly’s oral orforglipron (Foundayo) was approved in the US on April 1, 2026; and Lilly said on July 23, 2026 that it plans to submit retatrutide to the FDA in the first quarter of 2027. See our pages on orforglipron and retatrutide.
• Other mechanisms: Boehringer’s survodutide (landscape) and Amgen’s MariTide (landscape) aim at weight loss through different routes.

What to watch

1. The FDA decision on CagriSema, expected by Novo in late 2026, and the label that results.
2. REDEFINE 3, a cardiovascular outcomes trial of about 7,100 adults (estimated primary completion September 2027 on ClinicalTrials.gov).
3. A higher-dose Phase 3 (CagriSema 2.4/7.2 mg), with readout expected in the first half of 2028, and REDEFINE 11, expected in the first half of 2027.
4. Zenagamtide’s Phase 3 AMAZE program, which Novo’s August 2026 report lists as initiated. Its heart failure outcomes trial (HF-POLARIS, about 5,600 patients) is expected to read out in the second half of 2029, and a type 2 diabetes comparison with semaglutide (AMAZE 8) in the first half of 2029.

For comparison with the other leading drug, see our semaglutide landscape.

Recent developments

Updated November 4, 2026. Items are drawn from company announcements, regulators and trade press; links go to the sources.

• Aug 4, 2026: Novo’s half-year report said the Phase 3 AMAZE program for zenagamtide had been initiated, that REDEFINE 9 (lower CagriSema doses, 68 weeks) was completed with both doses beating placebo, and that a high-dose CagriSema Phase 3 had started. (Novo Nordisk 6-K)
• Jun 5, 2026: At ADA, Novo reported a 36-week Phase 2 trial of once-weekly injectable zenagamtide in 262 adults with type 2 diabetes: HbA1c fell by up to 1.71% (40 mg) vs 0.14% for placebo, and weight by up to 14.6% vs 2.1%. Adverse events were mostly mild to moderate and gastrointestinal. (Novo Nordisk via BioSpace)
• Feb 23, 2026: Novo reported REDEFINE 4: CagriSema 23.0% vs tirzepatide 25.5% weight loss at 84 weeks; the primary endpoint of non-inferiority was not met. (Novo Nordisk)
• Dec 18, 2025: Novo announced the US NDA submission for CagriSema. (Novo Nordisk via BioSpace)
• Jun 2025: Novo said it would advance subcutaneous and oral amycretin into Phase 3 after a Phase 1b/2a study showed up to 24.3% weight loss at 36 weeks. (BioSpace)

Upcoming catalysts

• Late 2026 (Novo guidance): FDA decision on CagriSema; no PDUFA date has been publicly stated in sources we reviewed.
• Q1 2027: Lilly’s planned retatrutide submission to the FDA.
• First half of 2027: REDEFINE 11 readout.
• First half of 2028: high-dose CagriSema Phase 3 readout.

Bottom line

CagriSema has produced weight loss in the low 20s percent in its pivotal trial, but the one head-to-head comparison with tirzepatide did not show non-inferiority, so the FDA decision and label will define where it sits. Zenagamtide is the longer-dated bet, with Phase 3 only recently started.

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This article is for informational and competitive-intelligence purposes only and is not medical advice. Approvals, labels and trial results change; verify details against current prescribing information and primary sources.