Compound reference
CagriSema
Also known as Cagrilintide/Semaglutide
Novo Nordisk's fixed-dose once-weekly combination of cagrilintide (a long-acting amylin analogue) and semaglutide (a GLP-1 agonist), pairing two satiety pathways. It posts roughly 20% weight loss in pivotal phase 3 and was filed for FDA approval in December 2025 — but it missed non-inferiority against tirzepatide in a head-to-head trial, and long-term cardiovascular data are still maturing.
- Half-life
- Once-weekly subcutaneous; both components have ~7-day half-lives
Investigational fixed-dose combination; not approved in the United States or European Union based on current source review.
Mode of action
CagriSema is a fixed-dose, once-weekly subcutaneous combination of two peptides that suppress appetite through different routes: cagrilintide, a long-acting analogue of the satiety hormone amylin (an agonist at amylin and calcitonin receptors that acts in the hindbrain, slows gastric emptying and blunts post-meal glucagon), and semaglutide, a GLP-1 receptor agonist. Pairing an amylin pathway with a GLP-1 pathway is the whole design rationale — two complementary satiety signals rather than one — and because both components have roughly week-long half-lives, the product is given as a single weekly injection at a fixed 2.4 mg / 2.4 mg dose.
Main intended effect
Chronic weight management in obesity or overweight, with glycemic control as a major secondary benefit in type 2 diabetes.
Areas of interest
Obesity is the lead indication and the basis of the FDA filing. Type 2 diabetes is the second major track, and a dedicated cardiovascular-outcomes trial (REDEFINE 3) plus head-to-head studies against tirzepatide round out a large phase 3 programme.
Evidence for intended effects
CagriSema has one of the larger, more recent controlled evidence bases in obesity — with an important nuance about expectations. A phase 1b study (Lancet 2021) first showed ~17% weight loss at 20 weeks, and a phase 2 type-2-diabetes trial (Lancet 2023) showed ~15.6% weight loss versus ~5.1% for semaglutide alone. The pivotal phase 3 REDEFINE 1 (NEJM 2025; 3,417 adults with obesity, without diabetes) reported about 20% mean weight loss versus 3% with placebo at 68 weeks, and REDEFINE 2 (NEJM 2025) showed ~13.7% in type 2 diabetes with 73.5% of patients reaching HbA1c ≤6.5%. But the open-label head-to-head REDEFINE 4 (2026 topline) did not meet its non-inferiority goal against tirzepatide 15 mg (23.0% vs 25.5%). Meta-analyses confirm CagriSema outperforms semaglutide alone, while the cardiovascular-outcomes trial (REDEFINE 3) is still running.
| Setting | Strongest evidence | Result |
|---|---|---|
| Obesity (no diabetes) | Phase 3 REDEFINE 1 (NEJM 2025) | ~20% mean weight loss vs ~3% placebo |
| Type 2 diabetes | Phase 3 REDEFINE 2 (NEJM 2025) | ~13.7% weight loss; 73.5% to HbA1c ≤6.5% |
| Head-to-head vs tirzepatide | REDEFINE 4 (2026 topline, open-label) | 23.0% vs 25.5% — non-inferiority not met |
| Cardiovascular outcomes | REDEFINE 3 | Ongoing |
Studied amounts (literature dosing context)
CagriSema is studied as a fixed once-weekly subcutaneous dose of cagrilintide 2.4 mg plus semaglutide 2.4 mg, reached by titrating both components over roughly 16 weeks. These are trial figures, not recommendations; the combination is not yet approved, there is no established prescribing dose, and this page does not provide dosing guidance.
Safety and regulatory status
Across the programme the safety pattern is the incretin-class norm: predominantly mild-to-moderate gastrointestinal effects (nausea, vomiting, diarrhea, constipation) plus injection-site reactions, more frequent than with semaglutide alone but generally manageable with titration; long-term and cardiovascular-outcome data are still maturing. Regulatorily, CagriSema is investigational: Novo Nordisk filed a New Drug Application with the FDA in December 2025 — the first GLP-1/amylin combination submitted for weight management, supported by the REDEFINE 1 trial — with review expected in 2026, but no approval has been granted. Its component semaglutide is separately approved, while cagrilintide remains investigational; any CagriSema obtained outside a clinical trial is unauthorised and of unverified content.
Sources
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)
Phase 3a randomized, double-blind, placebo-controlled trial (REDEFINE 1; Garvey and colleagues) enrolled 3,417 adults with obesity or overweight without diabetes across multiple countries; participants received once-weekly cagrilintide-semaglutide 2.4/2.4 mg (n=2,108), semaglutide 2.4 mg (n=302), cagrilintide 2.4 mg (n=302), or placebo (n=705) over 68 weeks. The combination achieved mean body-weight reduction of −20.4% versus −3.0% with placebo (difference −17.3 percentage points; 95% CI −18.1 to −16.6; p<0.001), significantly exceeding both monotherapy arms. Proportions achieving weight loss ≥5%, ≥20%, ≥25%, and ≥30% were all significantly higher with the combination versus placebo (p<0.001). Gastrointestinal adverse events occurred in 79.6% of combination-treated patients versus 39.9% on placebo, predominantly transient and mild-to-moderate.
Research Study of How Well CagriSema Works Compared to Semaglutide and Cagrilintide Alone in People With Overweight or Obesity (REDEFINE 1)
ClinicalTrials.gov registry record (NCT05567796; Novo Nordisk) for the Phase 3a REDEFINE 1 trial evaluating once-weekly CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) versus semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, and placebo in 3,417 adults with obesity or overweight without diabetes over 68 weeks. The trial is randomized, double-blind, and placebo-controlled with co-primary endpoints of percentage body-weight change and proportion achieving ≥5% weight loss. Results were subsequently published in the New England Journal of Medicine (2025) and are captured in the companion REDEFINE 1 NEJM source file.
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)
Phase 3a randomized, double-blind, placebo-controlled trial (REDEFINE 2; Davies and colleagues) enrolled 1,206 adults with overweight or obesity and type 2 diabetes (HbA1c 7–10%) across 12 countries; 904 received once-weekly cagrilintide-semaglutide 2.4/2.4 mg and 302 received placebo, with lifestyle intervention in both arms, over 68 weeks. Mean body-weight change was −13.7% with the combination versus −3.4% with placebo (difference −10.4 percentage points; 95% CI −11.2 to −9.5; p<0.001). A key secondary endpoint showed 73.5% of combination-treated patients achieved HbA1c ≤6.5% versus 15.9% on placebo. Gastrointestinal adverse events were reported by 72.5% of the combination group, mostly transient and mild-to-moderate; the trial demonstrated clinically meaningful weight and glycaemic benefit in a T2DM population where weight-loss responses are typically attenuated.
Cardiovascular Safety and Efficacy of Cagrilintide-Semaglutide (CagriSema 2.4/2.4 mg) in Participants With Established Cardiovascular Disease (REDEFINE 3)
Phase 3, randomized, double-blind, placebo-controlled event-driven cardiovascular outcomes trial (REDEFINE 3; NCT05669755; Novo Nordisk) of once-weekly cagrilintide-semaglutide 2.4/2.4 mg in participants with established cardiovascular disease. The primary endpoint is time to first three-point major adverse cardiovascular event (3P-MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), designed to test whether the combination's substantial weight-reduction effects translate into reduced cardiovascular event rates. The trial is ongoing; no results are yet available. This is the definitive cardiovascular safety and efficacy study required for potential broad cardiometabolic labeling of CagriSema.
Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial
Multicentre, randomized, double-blind, active-controlled Phase 2 trial (Frias and colleagues) conducted at 17 US sites enrolled 92 adults with type 2 diabetes (BMI ≥27 kg/m², on metformin ± SGLT2 inhibitor) over 32 weeks. Participants were randomized to once-weekly subcutaneous CagriSema 2.4/2.4 mg (n=31), semaglutide 2.4 mg (n=31), or cagrilintide 2.4 mg (n=30). The primary endpoint, HbA1c change, was −2.2 percentage points with CagriSema versus −0.9 with cagrilintide (difference −1.3; 95% CI −1.7 to −0.8; p<0.0001), though not significantly different from semaglutide (−1.8 pp; p=0.075). Secondary weight-loss endpoint strongly favoured CagriSema (−15.6% vs. −5.1% semaglutide and −8.1% cagrilintide; both p<0.0001). Adverse events were mostly mild-to-moderate gastrointestinal; no severe hypoglycaemia or fatal events were reported.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial
Phase 1b randomized, placebo-controlled, multiple-ascending-dose trial (Enebo and colleagues; Novo Nordisk) enrolled 95 adults with overweight or obesity (BMI 27–39.9 kg/m²) across six sequential cohorts receiving once-weekly cagrilintide 0.16–4.5 mg co-escalated with semaglutide 2.4 mg, or placebo plus semaglutide 2.4 mg, over 20 weeks. At week 20, weight loss with cagrilintide 2.4 mg + semaglutide was 17.1% versus 9.8% with semaglutide alone (difference −7.4%; 95% CI −11.2 to −3.5%), and with cagrilintide 4.5 mg was 15.4% versus 8.0% (difference −7.4%; 95% CI −12.8 to −2.1%). Adverse events, predominantly mild-to-moderate gastrointestinal in nature, occurred in 97% of cagrilintide-treated and 96% of placebo participants; no serious safety signals were identified, supporting CagriSema Phase 2 advancement.
Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis
Systematic review and meta-analysis pooling data from three randomized controlled trials enrolling 430 participants to compare cagrilintide monotherapy and the fixed combination of cagrilintide with semaglutide (CagriSema) against semaglutide or liraglutide monotherapy for obesity treatment. CagriSema produced significantly greater weight loss than semaglutide alone at 20–32 weeks, with a mean difference of approximately −9.1% body weight and −9.1 kg in absolute terms; by contrast, cagrilintide monotherapy achieved weight loss comparable to semaglutide or liraglutide (mean difference −1.8% and −1.9 kg), with significantly lower vomiting rates. Treatment-emergent and serious adverse events were broadly comparable between arms, although gastrointestinal events and vomiting were more frequent with CagriSema. The authors conclude that CagriSema outperforms semaglutide for weight reduction while cagrilintide monotherapy offers a similar weight-loss profile with a more tolerable gastrointestinal burden; notable limitations include high statistical heterogeneity (I² of 96–98%), a small number of included trials, and follow-up durations of 20–32 weeks that preclude conclusions about long-term durability.
https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.15859
Cagrilintide and CagriSema for weight reduction and metabolic risk modification in overweight or obesity: a systematic review and meta-analysis
Systematic review and meta-analysis published in a Springer endocrinology journal pooling data from randomized controlled trials of cagrilintide as monotherapy and in combination with semaglutide (CagriSema) in overweight or obese participants. The analysis examined effects on percentage and absolute body weight reduction alongside cardiometabolic risk markers including glycemic parameters. Results supported meaningful weight reduction with the CagriSema combination relative to semaglutide alone, while the cagrilintide monotherapy arm showed a more modest weight-loss profile; both regimens demonstrated a generally manageable safety profile with gastrointestinal events as the predominant adverse effect class. The authors conclude that cagrilintide and CagriSema represent clinically meaningful options for weight reduction and metabolic risk modification, acknowledging that the trial evidence base remains limited in size and follow-up duration, and that longer-term cardiovascular outcome data are needed.
https://link.springer.com/article/10.1007/s40200-024-01529-w
CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity; the primary endpoint was not achieved
Press release (Novo Nordisk) reporting topline results from REDEFINE 4, an 84-week open-label, head-to-head phase 3 trial randomizing 809 adults with obesity (mean baseline weight 114.2 kg) to once-weekly subcutaneous CagriSema 2.4/2.4 mg or tirzepatide 15 mg. The primary endpoint — non-inferiority of CagriSema on weight loss — was not met: weight loss was 23.0% vs 25.5% (efficacy estimand) and 20.2% vs 23.6% (treatment-regimen estimand) for CagriSema and tirzepatide, respectively. Gastrointestinal adverse events were the most common finding in both arms, were predominantly mild-to-moderate, and diminished over time. Novo Nordisk characterized CagriSema as the first GLP-1/amylin combination for obesity and announced follow-on trials (REDEFINE 11 and higher-dose studies) to pursue greater weight-loss potential; full peer-reviewed publication is pending.
https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916501
CagriSema demonstrated superior HbA1c reduction of 1.91%-points and weight loss of 14.2% in adults with type 2 diabetes in the REIMAGINE 2 trial
Press release (Novo Nordisk) reporting topline results from REIMAGINE 2, a 68-week phase 3 trial enrolling 2,728 adults with type 2 diabetes inadequately controlled on metformin ± SGLT2 inhibitor (approximately 40% using an SGLT2 inhibitor; mean baseline HbA1c 8.2%, body weight 101 kg). CagriSema 2.4/2.4 mg reduced HbA1c by 1.91 percentage points versus 1.76 points for semaglutide 2.4 mg (statistically significant), and reduced body weight by 14.2% versus 10.2% (statistically significant); 43% of CagriSema recipients achieved ≥15% weight loss and 24% achieved ≥20%, with no plateau observed at 68 weeks. Gastrointestinal adverse events were the most common finding and were predominantly mild-to-moderate. These are sponsor-reported topline results; full peer-reviewed publication is pending.
https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916481
Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP‑1 and amylin analogues for weight management
Novo Nordisk press release (December 18, 2025) announcing the New Drug Application submission to the FDA for CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg), a once-weekly subcutaneous combination representing the first co-formulation of a GLP-1 receptor agonist and a novel amylin analog. The proposed indication is chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity, as an adjunct to reduced-calorie diet and increased physical activity. Phase 3 REDEFINE 1 data (n=3,417) showed 22.7% mean weight loss at 68 weeks versus 2.3% on placebo; REDEFINE 2 evaluated the combination in adults with type 2 diabetes and excess weight. FDA review is expected in 2026.
Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP‑1 and amylin analogues for weight management
Novo Nordisk press release (December 18, 2025) announcing the submission of a New Drug Application to the FDA for CagriSema — a fixed-ratio once-weekly subcutaneous combination of cagrilintide 2.4 mg (a long-acting amylin analog) and semaglutide 2.4 mg — for chronic weight management in adults with obesity or overweight and at least one weight-related comorbidity. The NDA is supported by the REDEFINE 1 trial (n=3,417), in which CagriSema produced 22.7% mean body weight loss versus 2.3% with placebo at 68 weeks, with 91.9% of participants achieving at least 5% weight reduction. Cagrilintide as a monotherapy remains investigational; its regulatory status is contingent on the outcome of this combination NDA.