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CagriSema (Cagrilintide + Semaglutide Combination)
Also known as: Cagrilintide/Semaglutide, Cagri/Sema
Confidence
Updated 2026-03-20
CagriSema is a fixed-ratio combination of cagrilintide (a long-acting amylin analog) and semaglutide (a GLP-1 receptor agonist) developed by Novo Nordisk. It represents the next evolution of incretin-based obesity therapy, targeting two complementary appetite-regulation pathways. The REDEFINE Phase III trial program demonstrated up to 22.7% mean weight loss, and Novo Nordisk filed for FDA approval in 2026.
Class
Amylin Analog + GLP-1 Receptor Agonist (Combination)
Routes
Subcutaneous
Half-Life
Cagrilintide: ~7 days; Semaglutide: ~7 days (enabling co-formulated once-weekly injection)
CagriSema combines two distinct mechanisms: Cagrilintide is a long-acting analog of amylin, which is co-secreted with insulin from pancreatic beta cells. It activates amylin receptors (calcitonin receptor + RAMP complexes) in the area postrema and hindbrain to reduce appetite, slow gastric emptying, and suppress glucagon. Semaglutide activates GLP-1 receptors to stimulate insulin secretion, suppress glucagon, and reduce appetite centrally. The combination targets complementary satiety pathways for additive weight loss.
Half-Life
Cagrilintide: ~7 days; Semaglutide: ~7 days (enabling co-formulated once-weekly injection)
Bioavailability
Subcutaneous: ~80% (estimated, based on individual components)
Filed indication: chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity. Type 2 diabetes indication expected to follow.
REDEFINE 1 (Phase III): 22.7% mean weight loss at 68 weeks vs. 15.6% for semaglutide alone and 8.1% for cagrilintide alone. REDEFINE 2 (T2D): superior HbA1c reduction and weight loss vs. semaglutide. Over 8,000 participants across the REDEFINE program. Statistically significant superiority over individual components demonstrates additive benefit of dual pathway approach.
Human Studies
15
Animal Studies
20
GI adverse effects (nausea, vomiting, diarrhea) are the most common, consistent with both drug classes. Rates of GI events modestly higher than semaglutide alone in some analyses. Same class warnings as semaglutide: pancreatitis risk, medullary thyroid carcinoma (rodent signal), gallbladder events. Injection site reactions. Hypoglycemia risk when combined with insulin.
FDA filing accepted early 2026. PDUFA date pending. EMA filing also underway. If approved, would be the first amylin/GLP-1 combination product. Expected to be a branded product only — no compounding expected.
Drug Interactions: Same profile as semaglutide — caution with insulin, sulfonylureas, oral contraceptives. Delays gastric emptying (affects oral drug absorption). Monitoring: Weight, A1C, renal function, lipase/amylase, heart rate, GI symptom assessment. Research Gaps: Long-term cardiovascular outcomes data not yet available. Durability of weight loss maintenance. Comparison with tirzepatide. Effects in patients with heart failure (amylin effects on cardiac function).
Subcutaneous
Common Range
Cagrilintide 2.4 mg + Semaglutide 2.4 mg (fixed-ratio combination)
Timing
Once weekly, any time of day
Frequency
Weekly
Cycling
Dose escalation over ~16 weeks (similar to semaglutide titration schedule)
Storage
Refrigerated before first use
Important Note
Single injection combining both agents. Dose escalation schedule to minimize GI side effects. Expected to be available as prefilled pen.
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GLP-1 Receptor Agonist
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for type 2 diabetes and chronic weight management. It represents the leading edge of the incretin-based therapy revolution and has become one of the most widely prescribed peptide therapeutics globally. Available in both injectable (Ozempic, Wegovy) and oral (Rybelsus) formulations.
Dual GIP/GLP-1 Receptor Agonist
Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist approved for type 2 diabetes and chronic weight management. It represents a novel dual-incretin approach that has demonstrated superior weight loss and glycemic control compared to selective GLP-1 agonists in multiple Phase III trials.
Triple Incretin Receptor Agonist (GLP-1/GIP/Glucagon)
Retatrutide is a novel triple-agonist peptide developed by Eli Lilly that activates GLP-1, GIP, and glucagon receptors simultaneously. In Phase II trials, it produced the largest weight loss ever observed with a drug therapy — up to 24.2% body weight reduction at 48 weeks. The addition of glucagon receptor agonism to the dual GLP-1/GIP mechanism (tirzepatide) is theorized to enhance energy expenditure and hepatic fat reduction.
Disclaimer: This content is for educational and informational purposes only and does not constitute medical advice. Always consult with a licensed healthcare provider before starting, stopping, or modifying any peptide therapy. PeptideSupplierMatch does not prescribe, sell, or distribute peptides.
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