CagriSema
Quick Facts
- Full Name: Cagrilintide + Semaglutide Fixed-Dose Combination
- Aliases: CagriSema, Cagri-Sema
- Category: Weight Management / Metabolic Health / Type 2 Diabetes
- Components: Cagrilintide 2.4 mg (amylin analogue) + Semaglutide 2.4 mg
- Administration: Subcutaneous (once weekly; single co-formulated injection)
- Status: Phase 3 (REDEFINE program); NDA filed with FDA
- Titration: 16-week titration to maintenance doses
What It Does
CagriSema combines two complementary mechanisms in a single weekly injection: semaglutide's GLP-1 receptor agonism (satiety via hypothalamic signaling) with cagrilintide's amylin receptor agonism (gastric emptying delay, hepatic glucose regulation, satiety via hindbrain). The dual amylin + GLP-1 pathway produces additive weight loss exceeding either agent alone โ up to 22.7% body weight reduction.
Mechanism of Action
- Semaglutide (GLP-1R agonist): Reduces appetite via hypothalamic GLP-1 receptors; delays gastric emptying; improves insulin secretion; reduces glucagon
- Cagrilintide (amylin analogue): Activates amylin (IAPP) receptors in area postrema and nucleus accumbens โ reduces meal size; delays gastric emptying via complementary pathway; suppresses postprandial glucagon
- Complementary mechanisms: GLP-1 acts primarily via hypothalamus/reward centers; amylin acts primarily via hindbrain (NTS/AP) โ non-overlapping satiety pathways = additive effect
- Enhanced durability: Dual mechanism may reduce GLP-1 tolerance/plateau seen with semaglutide monotherapy
Dosing Protocols
16-Week Titration Schedule
| Week | Cagrilintide | Semaglutide |
|---|---|---|
| 1โ4 | 0.3 mg | 0.25 mg |
| 5โ8 | 0.6 mg | 0.5 mg |
| 9โ12 | 1.2 mg | 1.0 mg |
| 13โ16 | 1.8 mg | 1.7 mg |
| 17+ (Maintenance) | 2.4 mg | 2.4 mg |
- Once-weekly SubQ injection
- Rotate sites: abdomen, thigh, upper arm
Stacks Well With
- Typically used as standalone comprehensive therapy
- Previous Semaglutide or Tirzepatide users may transition for enhanced effect
Use Cases
- Obesity / Weight Management (up to 22.7% body weight reduction in trials)
- Type 2 Diabetes management
- Cardiovascular Risk Reduction
- Metabolic Syndrome
- GLP-1 plateau-breaking
Contraindications & Safety
- Medullary Thyroid Carcinoma or family history (absolute) โ GLP-1R agonist component
- MEN-2 (absolute)
- Type 1 Diabetes (absolute)
- History of pancreatitis โ relative contraindication
- Gallbladder disease โ rapid weight loss risk
- Common: Nausea, vomiting, diarrhea (mitigated by slow titration)
- Heart rate increase (GLP-1 component)
Storage
- Refrigerate 2โ8ยฐC; protect from light; single-use pen device
PubMed Research
Phase 3 REDEFINE Program โ June 2025 (NEJM simultaneous publications)
| Trial | Population | Comparator | Primary Weight Loss | Reference |
|---|---|---|---|---|
| REDEFINE-1 | BMI โฅ27 without T2D (n=3,417) | Placebo | -22.7% vs -2.3% (ฮ โ20.4 pp, P<0.001); ~40% achieved โฅ25% loss | DOI-10-1056-NEJMoa2502081 – REDEFINE-1 CagriSema Obesity (Garvey WT et al., NEJM 2025;392(25):2445-2456) |
| REDEFINE-2 | BMI โฅ27 + T2D (n=1,206) | Semaglutide 2.4 mg | -13.7% vs -10.6% (ฮ โ3.1 pp, P<0.001) โ superiority over active standard of care | PMID-40544432 – REDEFINE-2 CagriSema vs Semaglutide (Davies MJ et al., NEJM 2025) |
Key synthesis:
- REDEFINE-1 establishes CagriSema's ceiling weight-loss effect in non-T2D obesity โ competitive with tirzepatide 15 mg cross-trial (~22.5% in SURMOUNT-1, PMID-35658024 – SURMOUNT-1 Tirzepatide for Obesity).
- REDEFINE-2 demonstrates incremental superiority over semaglutide 2.4 mg monotherapy in T2D + obesity โ the clinically meaningful comparator showing cagrilintide adds real value beyond GLP-1 alone.
- Authorship note: REDEFINE-1 first author is Garvey WT; REDEFINE-2 first author is Davies MJ. Prior manifests that conflated the two should be corrected.
Regulatory positioning: NDA filed; FDA approval pending as of April 2026. If approved, positions as next-generation option in the "maximum-weight-loss" tier alongside tirzepatide 15 mg and Wegovy HD 7.2 mg.
Conference presentation context: The REDEFINE program was presented at two conferences in 2025 โ ADA 85th Scientific Sessions (June 22, 2025; Garvey + Davies joint session) with simultaneous NEJM publication, and subsequently at ObesityWeek 2025 (November 4-7, Atlanta) with REDEFINE-5 (East Asian population) and additional REDEFINE-1 post-hoc analyses. Full conference context: CONF-2025-ObesityWeek-REDEFINE-Sessions.
Sources
#weight-loss #metabolic-health #glp1 #amylin #peptide