CagriSema is Novo Nordisk's fixed-combination cagrilintide + semaglutide obesity drug — the company's bid to push the GLP-1 efficacy ceiling higher by adding amylin biology on top of the GLP-1 backbone.
The REDEFINE-1 and REDEFINE-2 Phase 3 trials read out across 2025 and 2026. The February 23, 2026 head-to-head readout against tirzepatide was the inflection point: 23% mean weight loss on CagriSema 2.4/2.4 mg vs 25.5% on tirzepatide 15 mg over 84 weeks, missing the non-inferiority primary endpoint and dropping NVO 15% intraday. Novo's Q1 2026 disclosures (May 6) confirmed a higher-dose CagriSema Phase 3 trial will start in H2 2026, but also disclosed that the company has discontinued the single-chamber co-formulation device project 'due to portfolio considerations' — the dual-chamber injectable system continues, the original FDA filing has been submitted, and a decision is expected late 2026. ECO 2026 in Istanbul (May 12–15) will deliver additional CagriSema data alongside Wegovy 7.2 mg and the Wegovy pill.
Stories here cover the REDEFINE readouts, the regulatory path, and the broader amylin-add-on field. See #cagrilintide for the amylin component and #amylin for class context.
Industry commentary May 22 framed Novo Nordisk's strategic response to retatrutide's TRIUMPH-1 readout as a two-track amylin strategy. CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) is the near-term play — Phase 3 REDEFINE-1 and REDEFINE-2 complete, FDA filing under review with decision expected late 2026, and Novo positioning the safety profile as the competitive edge after REDEFINE-4 missed non-inferiority versus tirzepatide 15 mg in February 2026. Amycretin (dual GLP-1/amylin agonist) is the long-term bet — AMAZE-12 Phase 3 began recruiting May 18 testing the dual agonist for weight maintenance, with Phase 1 results showing 22% weight loss at 36 weeks weekly subcutaneous and 13.1% at 12 weeks oral. The CagriSema higher-dose Phase 3 starts H2 2026; REDEFINE-11 reads out H1 2027. Combined, the amylin axis is structurally Novo's most direct response to Lilly's triple-agonist mechanism — adding amylin tone (slower gastric emptying, satiety persistence, weight-maintenance) rather than competing on glucagon-driven energy expenditure.
Novo Nordisk's CagriSema REDEFINE 1 cardiovascular sub-analyses, presented at ECO 2026 on Thursday May 14, layered onto the May 12 body-composition data. At week 68, CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) reduced systolic blood pressure by 10.9 mmHg vs 8.8 with semaglutide alone and 2.1 with placebo. High-sensitivity C-reactive protein dropped 68.9% vs 55.4% (semaglutide) and 16.0% (placebo). The 10-year predicted atherosclerotic cardiovascular disease risk decreased meaningfully on CagriSema versus all comparators, with fewer participants on CagriSema falling into the intermediate-to-high-risk category. The sub-analyses sharpen the combination-therapy case beyond the 22.7% mean weight-loss headline.
A second body-composition substudy from REDEFINE 1 presented May 14 at ECO 2026 broke out the DXA subgroup by treatment arm. At week 68, CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) produced -23.9% weight reduction in the DXA subgroup, compared with -16.6% on semaglutide 2.4 mg alone, -15.0% on cagrilintide 2.4 mg alone, and -2.8% on placebo. The fat-mass-to-lean-tissue ratios were favorable across all active arms: 66.9% fat-mass contribution on CagriSema, 69.7% on semaglutide, 62.9% on cagrilintide. The cagrilintide monotherapy arm is the first head-to-head body-composition signal for amylin-only therapy at clinically meaningful weight-loss levels — relevant to Zealand and Roche's petrelintide Phase 3 program and the broader amylin-versus-incretin debate.
Novo Nordisk's CagriSema REDEFINE 1 treatment-target analysis presented as an oral presentation at ECO 2026 on May 12 reported that the cagrilintide + semaglutide combination drove a higher percentage of participants to clinically meaningful BMI and waist-to-height ratio (WHtR) targets than any monotherapy or placebo arm. 50.7% of CagriSema-treated participants reached BMI <30 at week 68 vs 10.2% on placebo, and participants reaching BMI <27 plus WHtR <0.53 showed normalization of cardiometabolic parameters at higher rates than non-achievers. A companion REDEFINE 1 cardiovascular risk analysis scheduled for May 14 ECO presentation tracks predicted atherosclerotic CVD risk reduction. The data complements the May 12 body-composition substudy (35.7% fat-mass loss vs 14.4% lean tissue loss).
A prespecified body-composition substudy of REDEFINE 1 presented at ECO 2026 reported that 252 participants on CagriSema 2.4 mg/2.4 mg (semaglutide + cagrilintide) achieved a 35.7% relative reduction in fat mass and a 14.4% reduction in lean soft-tissue mass at week 68 — compared with 5.7% and 4.3% on placebo. The headline 22.7% mean weight reduction in REDEFINE 1 (NEJM publication June 2025) thus broke down with a fat-mass-to-lean-tissue ratio of roughly 2.5:1, a more favorable body-composition profile than the typical 1.5-2:1 ratio reported for GLP-1 monotherapy. The data builds the case for combination amylin-GLP-1 therapy as preferentially fat-selective.
Novo Nordisk CEO Mike Doustdar told CNBC May 6 that the Wegovy brand now holds 65% of all new US GLP-1 prescriptions and characterized the moment as a 'turnaround situation' for the franchise. The Q1 print also disclosed that Novo has terminated the single-chamber CagriSema co-formulation project 'due to portfolio considerations' — the dual-chamber injectable system continues, with the original FDA filing already submitted and a decision expected late 2026. The CEO insisted plans for the CagriSema launch remain on track despite the device change. CNBC also documented LifeMD's new-patient volume jumping from 300–400/day before the Wegovy pill launch to 600–1,000/day after.
Novo Nordisk confirmed in its Q1 2026 commentary that a higher-dose CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) Phase 3 trial will start in the second half of 2026, in response to the February 23 readout where the lower-dose 2.4/2.4 mg arm achieved 23% mean weight loss vs. 25.5% on tirzepatide 15 mg over 84 weeks — failing the non-inferiority primary endpoint. The original CagriSema FDA filing is already submitted with a decision expected in late 2026; the higher-dose program is meant to position Novo for a more competitive head-to-head against tirzepatide before the retatrutide TRIUMPH readouts arrive. ECO 2026 in Istanbul (May 12–15) will deliver additional CagriSema data alongside Wegovy 7.2 mg.
Novo Nordisk announced April 28 that it will present 52 abstracts at the European Congress on Obesity (ECO 2026, Istanbul, May 12–15), including new data from the REDEFINE 1 trial of CagriSema (cagrilintide 2.4 mg/semaglutide 2.4 mg): body composition and muscle strength, achievement of BMI/waist-to-height ratio targets, and cardiovascular risk reduction. Additional presentations will cover higher-dose Wegovy (semaglutide 7.2 mg), the Wegovy pill (oral semaglutide 25 mg) from OASIS 4 and ORION trials, and obesity treatment outcomes in women. The disclosure sets up a significant amylin/GLP-1 combination data event exactly as Zealand and Roche's amylin-only petrelintide moves into Phase 3.
C&EN published a comprehensive April 2026 feature examining whether amylin analogs — Novo's cagrilintide, Lilly's eloralintide, and Roche/Zealand's petrelintide — can carve meaningful share in a market dominated by semaglutide and tirzepatide. Wall Street initially expected amylin candidates to differentiate on muscle preservation and reduced GI side effects, but as Phase 2 readouts arrive investor enthusiasm has cooled. CagriSema Phase 3 head-to-head against tirzepatide is the make-or-break readout for Novo Nordisk's amylin strategy.
The FLOW trial showed semaglutide reduced major kidney events by 24%, and retatrutide demonstrated up to 28.7% weight loss in TRIUMPH-4. The full pipeline including CagriSema, MariTide, and survodutide was presented.
Novo Nordisk's long-acting amylin analog produced significant weight loss as standalone treatment in a 68-week double-blind trial, strengthening its profile ahead of the CagriSema FDA decision.
Industry analysis highlights CagriSema (cagrilintide + semaglutide) Phase 3 data showing 14.2% weight loss in type 2 diabetes adults, positioning it as a major Novo Nordisk pipeline asset.