OnePin Peptide Library · Weight
CagriSema
Cagrilintide + Semaglutide
CagriSema is the Novo Nordisk fixed-dose combination of Cagrilintide (long-acting amylin analog) and Semaglutide (GLP-1 receptor agonist) developed for chronic weight management. The two compounds are co-formulated in a single weekly subcutaneous injection. The REDEFINE program is the Phase 3 clinical development pathway, with REDEFINE 1 and REDEFINE 2 trials evaluating efficacy in obesity and obesity with type 2 diabetes respectively.
Same day each week. Inject into abdomen, thigh, or upper arm. Rotate sites. Pen device formulation expected at approval. Take with a meal during titration.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
CagriSema's mechanism combines two complementary appetite-regulating pathways:
Semaglutide (GLP-1 RA)
Same mechanism as standalone Wegovy/Ozempic. GLP-1 receptor agonism in pancreas (glucose-dependent insulin secretion), GI tract (delayed gastric emptying), and hypothalamus (appetite reduction). Lipidated peptide with weekly half-life.
Cagrilintide (Amylin Analog)
Long-acting analog of pancreatic amylin (also called islet amyloid polypeptide / IAPP). Acts at amylin receptors (combinations of calcitonin receptor + RAMP1/2/3 accessory proteins) in brainstem area postrema. Slows gastric emptying, suppresses glucagon, and produces meal-termination signaling distinct from but complementary to GLP-1.
Dual Axis Synergy
GLP-1 + amylin agonism activates two independent appetite-regulation circuits. REDEFINE Phase 3 data show this produces larger weight loss than GLP-1 alone (~22% body weight reduction at higher doses, vs ~15% for semaglutide monotherapy in comparable populations).
Single Weekly Injection
Both components co-formulated for weekly SubQ administration. Convenience similar to single-component GLP-1 RAs.
Lipidation Strategy
Both peptides use fatty-acid albumin-binding for extended half-life - shared with semaglutide and other long-acting GLP-1 RAs.
NEVER Stack with Other GLP-1 or Amylin Drugs
Already a combination - additional GLP-1 RAs (Tirzepatide, Liraglutide, etc.) or amylin analogs would be redundant + additive risk.
What to expect
Week 1-4: appetite suppression begins, GI side effects most prominent.
Month 2-6: peak weight loss velocity. Sustained 8-15% reduction typical at maintenance.
Month 12-18: -22% peak weight loss at 2.4/2.4 mg per REDEFINE 68-week data.
Evidence
Interactions & stacking
What's safe to combine, and what belongs in a separate pin.
Keep separate
Side effects & safety
Commonly reported
- Nausea (most common, dose-dependent, often improves)
- Vomiting (more common at higher tiers)
- Diarrhea or constipation
- Decreased appetite (intended)
- Injection site reactions
- Headache
- Fatigue (early dose tiers)
- Mild gallbladder symptoms
Less common & notes
- Pancreatitis (class warning - personal/family history is contraindication).
- Gallbladder disease, cholelithiasis - rapid weight loss is itself a gallstone risk factor.
- Acute kidney injury secondary to dehydration.
- Diabetic retinopathy worsening with rapid glucose lowering (rare).
- Medullary thyroid carcinoma class signal from rodent studies.
- Hypoglycemia in patients on insulin or sulfonylureas.
- Long-term safety beyond Phase 3 trial duration not yet established.
- Cagrilintide-specific: muscle/lean mass preservation appears comparable to semaglutide alone but ongoing analysis.
- Oral contraceptives may be less reliable during dose initiation and escalation: delayed gastric emptying (GLP-1 / amylin) can reduce oral drug absorption - Tirzepatide carries an FDA label warning to use a backup or non-oral method for 4 weeks after starting and after each dose increase.
Pharmacokinetics
Storage. Refrigerate. Pen device formulations have specific post-loading expiration windows. Lyophilized research-grade reconstituted: 28 days refrigerated. Light-sensitive.
Regulatory status
Investigational - not yet FDA-approved or EMA-approved as of this writing. Phase 3 REDEFINE program completed; regulatory submissions in progress. Outside approved jurisdictions, sale of research-grade CagriSema follows the standard research-chemical legal framework. WADA prohibition applies to peptide hormones generally.
Put it to work
Calculate, log & track
Open CagriSema straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
Open CagriSema in the app →Go deeper
The guide & community
The complete CagriSema walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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