{"id":"cagrisema","name":"CagriSema","aliases":["cagrilintide/semaglutide","cagrilintide-semaglutide","NN9838"],"url":"https://lyoresearch.com/compounds/cagrisema","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"CagriSema is a once-weekly co-injection of cagrilintide, an amylin analogue, with semaglutide 2.4 mg. In REDEFINE 1, a 3,417-person phase 3 trial published in 2025, it produced 20.4% average weight loss at 68 weeks against 3.0% on placebo; in people with type 2 diabetes the figure was 13.7%. Both trials are peer-reviewed. It is not yet approved anywhere, and anything sold under the name is not the trial product.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"2 phase 3 RCTs published (n=3,417; n=1,206); 2 further phase 3 topline (Sep 2026)","regulatory_status":"Investigational (filed)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A co-formulation of two molecules: see cagrilintide and semaglutide"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly (two injections)","half_life":"A combination: cagrilintide about 7–8 days, semaglutide about 1 week","licensed_regimen":null,"product":null,"source":{"title":"Enebo LB, et al. Lancet 2021 (cagrilintide with semaglutide 2.4 mg, phase 1b)","url":"https://www.sciencedirect.com/science/article/abs/pii/S014067362100845X"}},"outcomes":[{"outcome":"Body weight (obesity without diabetes)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (n=3,417, 68 wk)","evidence":"REDEFINE 1 randomised 2,108 people to the combination, 302 to semaglutide alone, 302 to cagrilintide alone and 705 to placebo. The combination lost 20.4% against 3.0% on placebo; the single agents landed in between. Published in the New England Journal of Medicine.","references":[{"citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"}],"verbatim":{"text":"The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points; 95% confidence interval, -18.1 to -16.6; P<0.001).","citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"}},{"outcome":"Body weight (obesity with type 2 diabetes)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (n=1,206, 68 wk)","evidence":"REDEFINE 2: 13.7% loss against 3.4% on placebo — the usual smaller effect in people with diabetes. Nearly three-quarters reached an HbA1c of 6.5% or below.","references":[{"citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}],"verbatim":{"text":"The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points; 95% confidence interval, -11.2 to -9.5; P<0.001).","citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}},{"outcome":"Blood glucose (HbA1c) in type 2 diabetes","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (n=1,206)","evidence":"In REDEFINE 2, 73.5% of people on the combination reached an HbA1c of 6.5% or less against 15.9% on placebo.","references":[{"citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}],"verbatim":{"text":"The percentage of patients who had a glycated hemoglobin level of 6.5% or less was 73.5% in the cagrilintide-semaglutide group and 15.9% in the placebo group.","citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}},{"outcome":"Body weight (vs tirzepatide 5 mg, type 2 diabetes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT topline (REIMAGINE 5, 60 wk)","evidence":"Novo Nordisk press release, 21 September 2026: in adults with type 2 diabetes not controlled on metformin, an SGLT2 inhibitor or both, CagriSema 1.0 mg/1.0 mg produced 12.4% weight loss at 60 weeks against 9.1% on tirzepatide 5 mg, with HbA1c reductions of 1.71 and 1.67 points (non-inferior). Both arms were low doses: tirzepatide's lowest maintenance dose, and less than half the 2.4 mg/2.4 mg of CagriSema used in REDEFINE 1. Efficacy estimand; enrolment not stated; not peer-reviewed, so B. The same release reports 21.0% against 2.0% on placebo at 68 weeks for the 1.0 mg/1.0 mg dose in obesity (REDEFINE 9).","references":[{"citation":"Novo Nordisk. CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (with REDEFINE 9 topline).","where":"Press release, 21 Sep 2026","url":"https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916774"}]},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"Both phase 3 RCTs","evidence":"Four in five people on the combination had gastrointestinal events in REDEFINE 1, against two in five on placebo; the same pattern in REDEFINE 2 (72.5% vs 34.4%). Mostly transient and mild to moderate, as with the parent drugs.","references":[{"citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"},{"citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}],"verbatim":{"text":"Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity.","citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational; no EMA authorisation at review."},{"region":"United States","status":"Not approved","note":"Novo Nordisk filed a New Drug Application for weight management in December 2025 and says it expects an FDA decision in the fourth quarter of 2026. Not approved at review; products sold under the name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Cagrilintide is unapproved, so the combination falls under S0 (non-approved substances) even though semaglutide is not banned."}],"faq":[{"q":"How much weight do people lose on CagriSema?","a":"20.4% on average at 68 weeks in adults with obesity and without diabetes, against 3.0% on placebo; 13.7% in adults with type 2 diabetes. Both figures are from published phase 3 trials."},{"q":"Is CagriSema better than tirzepatide?","a":"Unknown at full dose. Its 20.4% is close to tirzepatide's 20.9% in SURMOUNT-1, but cross-trial numbers are unreliable, and the direct comparison in obesity (REDEFINE 4) has not reported. In REIMAGINE 5, announced by press release in September 2026, low-dose CagriSema beat tirzepatide's lowest maintenance dose in people with type 2 diabetes: 12.4% against 9.1% at 60 weeks."},{"q":"Is CagriSema available?","a":"No. It is not approved anywhere. Vials sold online under the name are unlicensed and not the trial product."},{"q":"Why did the result disappoint?","a":"Novo Nordisk had projected about 25% weight loss from its phase 2 data. The phase 3 delivered 20.4% — still the best published combination result, but the gap moved the company's share price more than it moved the science."}],"references":[{"cite":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/","note":"3,417 randomised, 68 weeks. NCT05567796."},{"cite":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/","note":"1,206 randomised, 68 weeks. NCT05394519."},{"cite":"Novo Nordisk. CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (with REDEFINE 9 topline).","where":"Press release, 21 Sep 2026","url":"https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916774","note":"REIMAGINE 5: 60 weeks, type 2 diabetes, vs tirzepatide 5 mg. REDEFINE 9: 68 weeks, obesity, vs placebo. Topline, efficacy estimand; not peer-reviewed. States the US filing of December 2025 and a decision expected in Q4 2026."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"REIMAGINE 5 and REDEFINE 9 topline results (press release, 21 Sep 2026) added as a new row against tirzepatide 5 mg, graded B; US filing status updated (filed December 2025, decision expected Q4 2026). Overall grade unchanged."},{"date":"2026-09-23","note":"Initial publication from the two published REDEFINE phase 3 trials. Overall grade B (investigational, unapproved); the trial rows are graded A on their own certainty."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}