What it is
Cagrilintide is a lab-made copy of amylin. Amylin is a hormone. The pancreas releases it along with insulin after meals. Amylin slows how fast the stomach empties. It also tells the brain you are full. It does this by a different route than GLP-1 drugs. Novo Nordisk designed cagrilintide to last a week. They also made it so it does not clump. Clumping is a known problem with natural amylin.
On its own, it caused slightly more weight loss than liraglutide in a mid-stage trial. It has also been combined with semaglutide in one pen. That combination is called CagriSema. In the main Phase 3 trial, CagriSema caused about 20% weight loss. Neither cagrilintide nor CagriSema is approved yet. CagriSema is under FDA review.
Cagrilintide (NNC0174-0833) is a 37-residue amylin analogue with substitutions at residues prone to β-sheet aggregation and a C20 fatty diacid attached through a linker for albumin binding. It is a dual amylin and calcitonin receptor agonist (DACRA), acting on calcitonin receptor and RAMP-associated amylin receptor complexes in the area postrema and hypothalamus. In a Phase 1b study its half-life was 159–195 hours, against 145–165 hours for co-administered semaglutide. The combination rationale is additive appetite suppression through non-overlapping central pathways, with the amylin component possibly offsetting some GLP-1 receptor agonist tolerance.
Who made it and when
Novo Nordisk made it in the mid-2010s. The company published the chemistry in 2021. It then tested the drug alone and with semaglutide. The large Phase 3 trials are called REDEFINE. They started in 2022. The first results came out in December 2024. Novo Nordisk asked the FDA to approve CagriSema in December 2025. In September 2026 the company said it expects the US decision in the last 3 months of 2026.
Kruse and colleagues at Novo Nordisk described the medicinal chemistry in 2021. Phase 2 monotherapy (n=706) reported in 2021; Phase 2 CagriSema in T2D reported in 2023. The REDEFINE program includes REDEFINE 1 (obesity), REDEFINE 2 (obesity with T2D), REDEFINE 3 (cardiovascular outcomes, event-driven) and REDEFINE 4 (head-to-head vs tirzepatide). Novo Nordisk announced on 2025-12-18 that it had submitted a New Drug Application for once-weekly CagriSema (cagrilintide 2.4 mg and semaglutide 2.4 mg) for weight management in adults with obesity, or overweight with comorbidities. No FDA approval had been announced as of 2026-11-01; the company stated on 2026-10-29 that CagriSema is not approved in the United States or anywhere else, and its 2026-09-21 Capital Markets Day deck guided to a US decision in the fourth quarter of 2026. Patents are held by Novo Nordisk.
What the data say
Alone, the highest dose of cagrilintide caused about 11% weight loss in 26 weeks. That was slightly more than liraglutide.
With semaglutide, the Phase 3 REDEFINE 1 trial showed about 20% weight loss over 68 weeks. Semaglutide alone gave 15%. A dummy treatment (placebo) gave 3%. If everyone had stayed on treatment, the figure was about 23%. Many people did not stay on the full dose.
In people with diabetes, CagriSema caused about 14% weight loss. In a head-to-head trial, it did not do as well as tirzepatide.
Three more trials were published in 2026. In people with type 2 diabetes on metformin, CagriSema lowered long-term blood sugar (HbA1c) a little more than semaglutide alone. In people on insulin, it lowered HbA1c by 2.3 points versus 0.7 with placebo. In Japan and Taiwan, it gave about 18% weight loss versus 12% with semaglutide. Stomach and gut side effects were about twice as common as with placebo across the diabetes trials.
Phase 2 monotherapy: 4.5 mg gave −10.8% at 26 weeks vs −3.0% placebo. REDEFINE 1 (n=3,417): CagriSema −20.4% vs semaglutide 2.4 mg −14.9%, cagrilintide 2.4 mg −11.5%, placebo −3.0% at 68 weeks (treatment-policy); −22.7% vs −2.3% by trial-product estimand. The flexible-dosing protocol meant only 57.3% of CagriSema participants were on the full 2.4/2.4 mg dose at the end of treatment. REDEFINE 2 (T2D, n=1,206): −13.7% vs −3.4%. REDEFINE 4 (n=809, open-label, 84 weeks) did not show non-inferiority to tirzepatide 15 mg (−23.0% vs −25.5% if all adhered). Gastrointestinal adverse events were the main tolerability issue, reported in 79.6% vs 39.9% on placebo in REDEFINE 1. A post hoc analysis of REDEFINE 1 reported systolic blood pressure −10.9 mmHg with CagriSema vs −2.8 mmHg with placebo (Verma et al., Hypertension 2026;83(2):e26055).
Phase 3a publications in 2026: REIMAGINE 2 (Buse et al., Lancet Diabetes Endocrinol 2026;14(8):662–677; n=2,713 with T2D on metformin ± SGLT2 inhibitor, 68 weeks) reported HbA1c −1.91 vs −1.75 percentage points for CagriSema 2.4/2.4 mg vs semaglutide 2.4 mg (ETD −0.16, 95% CI −0.27 to −0.05, efficacy estimand) with adverse events in 86.9% vs 81.2%; REIMAGINE 3 (Rosenstock et al., Lancet 2026;408:38–51; n=274 on basal insulin, 40 weeks) reported HbA1c −2.33% vs −0.66% with placebo (ETD −1.68, −1.95 to −1.41) and no severe hypoglycaemia; REDEFINE 5 (Yamauchi et al., Lancet Diabetes Endocrinol 2026;14(6):450–462; n=331, Japan and Taiwan, 68 weeks) reported −18.4% vs −11.9% body weight with semaglutide (ETD −6.5 points, −8.4 to −4.6, trial-product estimand). A meta-analysis of 6 RCTs in T2D (Kow et al., Diabetes Obes Metab 2026, doi 10.1111/dom.71485) put the relative risk of gastrointestinal adverse events at 2.27 vs placebo. Company data, not peer reviewed: Novo Nordisk’s September 2026 deck gives REDEFINE 9 weight loss at 68 weeks as 20.95% (1.0/1.0 mg) and 20.75% (1.7/1.7 mg) by the efficacy estimand, with discontinuation for adverse events in 4.9%, 2.9% and 4.9% (placebo); primary results are due as a poster at ObesityWeek on 2026-11-15.
Regulatory picture
Cagrilintide is not approved anywhere. CagriSema was sent to the FDA for review in December 2025. It was still under review on 1 November 2026. Novo Nordisk said on 29 October 2026 that CagriSema is not approved in the United States or anywhere else, and expects the US decision in the last 3 months of 2026. Cagrilintide on its own is in late-stage (Phase 3) trials called RENEW; the company says it expects to launch it in 2028 if approved. The FDA says cagrilintide cannot legally be used in compounding in the United States. It is not one of the 6 peptides covered by the US health department’s draft policy of October 2026 that eases enforcement on some compounded peptides. Compounding means pharmacies mixing their own versions. Cagrilintide is not part of any FDA-approved drug. Anything sold online under this name is an unapproved drug.
Cagrilintide is investigational under IND. It is not a component of an approved product and has no USP monograph. FDA’s guidance page on unapproved GLP-1 drugs states that cagrilintide cannot be used in compounding under federal law, so neither the 503A nor the 503B pathway is available. FDA’s page carried a “current as of 10/01/2026” date when checked for this update, with that wording unchanged, and no FDA warning letter in the 2026-08-24 round to “research use” sellers named cagrilintide as a product. Cagrilintide is also not among the six peptides covered by the HHS draft enforcement-discretion policy of 2026-10-30 (docket HHS-OASH-2026-0496). The CagriSema NDA was submitted to the FDA in December 2025. As of 2026-11-01 no decision had been announced: Novo Nordisk’s 2026-09-21 Capital Markets Day deck expects the “CagriSema US decision for weight management” in the fourth quarter of 2026, the REDEFINE 11 readout in the first quarter of 2027 and the CagriSema HD readout in the first half of 2028, and lists the cagrilintide monotherapy programme RENEW as “Phase 3 ongoing, Expected launch 2028”; on 2026-10-29 the company stated that “CagriSema is not approved in the United States or anywhere else”. Registered since 2025–2026: RENEW 1 and RENEW 2 (NCT07220642, NCT07220759; cagrilintide vs placebo, 64 weeks), NCT07564414 (CagriSema at two dose levels vs semaglutide, Phase 3, recruiting, 2,500 planned, 72 weeks) and NCT07745504 (RENEW 4, cagrilintide in two presentations vs placebo, recruiting, 285 planned). Any approval would cover the fixed-dose combination product, not cagrilintide as a stand-alone drug.
