Peptide Schedule
CagriSema37 residues (approx.)KCNTATCATQRLANFLVHSSNNFGPILPPTNVGSNTYEach bubble = one amino acid. Size = residue mass. Color = chemical class.Uses closest standard amino acids for non-standard residues.CagriSema
Benefits
About CagriSema
CagriSema is a first-in-class, fixed-dose combination of cagrilintide (a long-acting amylin analog) and semaglutide (a GLP-1 receptor agonist) developed by Novo Nordisk. By targeting two distinct appetite-regulating pathways — amylin and GLP-1 — in a single weekly injection, CagriSema produces greater weight loss than either component alone. In the Phase 3 REDEFINE 1 trial, participants without diabetes lost an average of 22.7% of their body weight over 68 weeks, with roughly 40% achieving at least 25% weight loss. REDEFINE 2 demonstrated 15.7% weight loss in adults with type 2 diabetes. Novo Nordisk has submitted an NDA to the FDA, positioning CagriSema as the next generation of obesity treatment.
Who Should Consider CagriSema
- Adults with BMI ≥30 (obesity)
- Adults with BMI ≥27 with at least one weight-related comorbidity
- Adults with obesity or overweight and type 2 diabetes
- Patients who have plateaued on GLP-1 monotherapy
- Individuals seeking greater weight loss than single-agent options
How CagriSema Works
CagriSema combines two complementary appetite-regulating mechanisms in a fixed-dose formulation. Cagrilintide is a long-acting analog of amylin, a hormone co-secreted with insulin from pancreatic beta cells. It activates amylin receptors (calcitonin receptor + RAMP complexes) in the area postrema and hypothalamus, reducing food intake by promoting early satiety and slowing gastric emptying. Semaglutide is a GLP-1 receptor agonist that mimics incretin signaling — it enhances glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and activates hypothalamic satiety centers. Together, these two pathways produce additive appetite suppression and greater weight loss than either agent alone, as confirmed by the REDEFINE 1 head-to-head comparison arms.
What to Expect
Initial titration phase. GI side effects (nausea, constipation) most common early. Mild appetite reduction may begin. Body adapts to dual amylin + GLP-1 activation.
Appetite suppression becomes more noticeable. Early weight loss of 2-5% expected. Nausea typically starts to subside as the dose stabilizes.
Continued titration with progressive appetite and hunger reduction. Steady weight loss accelerates. Blood glucose and insulin sensitivity improve in those with type 2 diabetes.
Full therapeutic dose. REDEFINE 1 showed 22.7% mean weight loss by week 68 (treatment-policy: 20.4%). About 40% of patients reached ≥25% loss and 23% reached ≥30%. GI side effects largely resolved.
Long-term maintenance at reduced body weight. Continued metabolic and cardiometabolic benefits expected while on therapy. Weight regain likely if treatment is stopped.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 0.5mg | Weekly |
| Moderate | 1.7mg | Weekly |
| Aggressive | 2.4mg | Weekly |
Note: Fixed-ratio combination of cagrilintide 2.4 mg + semaglutide 2.4 mg in a single pre-filled pen. Titrate over 16 weeks: 0.25 mg each (wk 1-4), 0.5 mg (wk 5-8), 1.0 mg (wk 9-12), 1.7 mg (wk 13-16), then 2.4 mg maintenance. Not yet FDA-approved — Phase 3 REDEFINE program ongoing. NDA submitted to FDA.
How to Inject CagriSema
Inject subcutaneously once weekly using the pre-filled pen, on the same day each week. Injection sites include the abdomen, thigh, or upper arm — rotate sites between injections. Can be taken at any time of day, with or without food. Follow the 16-week titration schedule: 0.25 mg/0.25 mg (weeks 1-4), 0.5 mg/0.5 mg (weeks 5-8), 1.0 mg/1.0 mg (weeks 9-12), 1.7 mg/1.7 mg (weeks 13-16), and 2.4 mg/2.4 mg maintenance from week 17 onward.
Cycling Protocol
Based on 68-week REDEFINE Phase 3 trial design. Intended for long-term use. Weight regain expected upon discontinuation, consistent with GLP-1 agonist class. Titrate over 16 weeks before reaching maintenance dose.
Pharmacokinetics
Source: Phase 1b trial (Enebo et al., Lancet 2021, PMID 33894838): semaglutide t½ 145-165h, cagrilintide t½ 159-195h
Loading the interactive decay curve.
Side Effects
Gastrointestinal events are the most common side effects, occurring in ~80% of participants (vs ~40% placebo). Nausea (55%), constipation (31%), vomiting (26%), and diarrhea are typical. Most GI effects are mild to moderate and diminish over time, especially with proper titration. Discontinuation due to adverse events was ~6% in REDEFINE 1. Injection site reactions may occur.
Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
- History of pancreatitis
- Pregnancy or breastfeeding
- Known hypersensitivity to cagrilintide, semaglutide, or any excipients
- Severe gastrointestinal disease (e.g., gastroparesis)
- End-stage renal disease (insufficient data)
Drug Interactions
- Insulin and sulfonylureas — increased hypoglycemia risk; dose adjustment may be needed
- Oral medications — absorption may be delayed due to slowed gastric emptying from both components
- Levothyroxine — monitor thyroid levels; GLP-1 agonists may alter exposure
- Warfarin — monitor INR more frequently during initiation and dose changes
- Oral contraceptives — delayed absorption possible due to gastric emptying effects; no confirmed clinical interaction but caution is advised
Storage & Stability
Molecular Profile
Related Peptides
References
- REDEFINE 1: Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (NEJM 2025)PubMed 40544433
- REDEFINE 2: Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (NEJM 2025)PubMed 40544432
- Phase 2 Trial: Cagrilintide 2.4 mg + Semaglutide 2.4 mg in Type 2 Diabetes (Lancet 2023)PubMed 37364590
- Phase 1b PK/PD: Cagrilintide + Semaglutide for Weight Management (Lancet 2021)PubMed 33894838
- Systematic Review and Meta-Analysis: Cagrilintide Alone and as CagriSema (Indian J Endocrinol Metab 2024)Review