Evidence Grade C — Moderate human evidence. 39 published studies, 28 human. 0 registered clinical trials.
Medically reviewed by a licensed medical professional
CagriSema is a single once-weekly injection combining cagrilintide (an amylin analogue) with semaglutide (a GLP-1 agonist), in Phase III development by Novo Nordisk. By targeting two different appetite-control pathways simultaneously, it aims to achieve greater weight loss than semaglutide alone. In the pivotal trial, it achieved 22.7% weight loss — comparable to tirzepatide's results.
CagriSema is also known by these brand and alternate names:
39 published studies: 28 human, 1 animal, 0 in-vitro, 25 reviews
CagriSema is in Phase III development (not yet approved). The pivotal REDEFINE-1 trial (3,417 patients, 68 weeks) reported 22.7% weight loss with CagriSema compared to 16.1% with semaglutide alone and 2.3% with placebo. The approximately 6 percentage point advantage over semaglutide alone demonstrates the additive benefit of the amylin component.
CagriSema represents the combination approach to obesity pharmacotherapy — targeting multiple pathways to achieve greater weight loss than monotherapy. Gastrointestinal side effects remain the most common adverse events. If approved, it would be the first injectable combination therapy for obesity.
CagriSema combines two complementary mechanisms: semaglutide's GLP-1 receptor-mediated appetite suppression with cagrilintide's amylin receptor-mediated satiety enhancement. The rationale is that simultaneously targeting two distinct brain pathways controlling food intake produces greater weight loss than either mechanism alone — similar to how combining different blood pressure medications produces greater effect than increasing the dose of one.
The REDEFINE-1 trial (3,417 patients) showed 22.7% weight loss with CagriSema compared to 16.1% with semaglutide alone — a roughly 6 percentage point advantage demonstrating the additive benefit of the amylin component. A regulatory filing was submitted in December 2025, with FDA review expected by approximately late 2026. Initial market expectations of approximately 25% weight loss were modestly overestimated. The actual 22.7% result is comparable to tirzepatide's 22.5% from its pivotal trial, though a head-to-head trial (REDEFINE-4) is ongoing and will provide the first direct comparison. Gastrointestinal side effects occurred in about 80% of patients (primarily nausea and diarrhoea), which is higher than semaglutide alone. If approved, CagriSema would be the first injectable combination therapy for obesity.
Health Canada Market Authorisation
CagriSema is a fixed-ratio combination of cagrilintide 2.4 mg and semaglutide 2.4 mg delivered in a single once-weekly subcutaneous injection, developed by Novo Nordisk. It represents the first injectable combination therapy targeting both amylin and GLP-1 receptor pathways for obesity treatment. The REDEFINE Phase 3 program is one of the largest obesity trial programs conducted to date, and the NDA was filed with the FDA on December 18, 2025, with regulatory review expected approximately Q4 2026.
CagriSema combines two complementary mechanisms: semaglutide's GLP-1 receptor-mediated appetite suppression (acting on hypothalamic GLP-1R neurons to reduce food intake and delay gastric emptying) with cagrilintide's amylin receptor-mediated satiety enhancement (acting on AMY1R and AMY3R receptors in the area postrema and hypothalamus). Phase 2 data demonstrated pharmacological synergy, with combination weight loss exceeding simple addition of individual components, likely through engagement of distinct but partially overlapping central satiety circuits.
The pivotal REDEFINE-1 trial (published in NEJM June 2025; NCT05567796; N=3,417) randomized patients 21:3:3:7 to CagriSema, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo over 68 weeks. Trial product estimand results: CagriSema -22.7%, semaglutide -16.1%, cagrilintide -11.8%, placebo -2.3%. Treatment policy estimand: CagriSema -20.4% versus placebo -3.0% (ETD -17.3 percentage points; P<0.001). Categorical outcomes (trial product): 97.6% achieved at least 5% weight loss, 60.2% achieved at least 20%, and 40.4% achieved at least 25%. REDEFINE-2 (NCT05394519; N=1,206 with T2D) showed -15.7% weight loss versus -3.1% placebo (P<0.001). REIMAGINE-2 (N=2,728 T2D) confirmed superiority over semaglutide alone for both HbA1c reduction (-1.91 percentage points) and weight loss (-14.2%). Gastrointestinal adverse events affected 79.6% of CagriSema patients versus 39.9% placebo; discontinuation due to adverse events was 6.0%.
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Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity. In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
