Weight GLP-1 + Amylin Fixed-Dose CombinationNot FDA-approved · investigational

CagriSema

Cagrilintide + Semaglutide

Evidence: Studied in humans. Example dose: finalize with a provider. Not a fact-check stamp.

0.25mg sema + 0.25mg cagri (titration start) – 0.25 mg Cagrilintide + 0.25 mg Semaglutide SubQ 1x weekly

Cagrilintide + Semaglutide Co-FormulationPhase 3 Investigational (REDEFINE)Weight Management Therapy

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.

Quick Start

Route

Subcutaneous injection

Start low

0.25mg sema + 0.25mg cagri… SubQ

Frequency

1x weekly

Timing

With food to mitigate GI side effects

Starting dose. 0.25mg sema + 0.25mg cagri (titration start)

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.

Tiered Protocols · lowest first

Conservative start

0.25mg sema + 0.25mg cagri (titration start) · Subcutaneous injection · 1x weekly

conservative starter

0.25mg sema + 0.25mg cagri (titration start)

1x weekly

Intermediate

Dual Amylin/GLP-1 Titration

0.25 mg Cagrilintide + 0.25 mg Semaglutide · SubQ · Weekly

human clinical trial · Frias JP et al. 2023 (Lancet, Vol 402)

Escalate both compounds simultaneously in 0.25mg/0.25mg increments every 4 weeks based on gastrointestinal tolerance.

0.25 mg Cagrilintide + 0.25 mg Semaglutide

Weekly

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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

Early

Days 1–7

Week 1-4: appetite suppression begins, GI side effects most prominent.

Mid

Weeks 2–4

Month 2-6: peak weight loss velocity. Sustained 8-15% reduction typical at maintenance.

Later

Weeks 4–12

Month 12-18: -22% peak weight loss at 2.4/2.4 mg per REDEFINE 68-week data.

Evidence

HumanPresent

AnimalPresent

In-vitroPresent

Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.

Route/frequency boundary: once-weekly subcutaneous CagriSema was studied with both components escalated to 2.4 mg; this does not establish the page’s 0.25 mg + 0.25 mg start.

Adults with type 2 diabetes and a BMI of 27 kg/m2 or higher on metformin with or without an SGLT2 inhibitor were randomly assigned (1:1:1) to once-weekly subcutaneous CagriSema, semaglutide, or cagrilintide (all escalated to 2·4 mg).

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. Lancet (London, England) · 2023 · PMID 37364590

Evidence scope. Human phase 2 trial in adults with type 2 diabetes and BMI at least 27 kg/m² on metformin with or without an SGLT2 inhibitor; all arms escalated to 2.4 mg.

Mechanism/class boundary: the exact coadministered combination pairs long-acting amylin analogue cagrilintide with GLP-1 analogue semaglutide.

Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management.

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. Lancet (London, England) · 2021 · PMID 33894838

Evidence scope. Human phase 1b combination trial in otherwise healthy adults with BMI 27.0-39.9 kg/m²; mechanism/class statement, not proof of every pathway detail on the page.

Primary safety at the 2.4 mg + 2.4 mg target: gastrointestinal adverse events were common and mainly transient and mild-to-moderate.

Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity.

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. The New England journal of medicine · 2025 · PMID 40544433

Evidence scope. Human phase 3a REDEFINE 1 trial in adults with overweight/obesity without diabetes; target dose 2.4 mg of each component, not the page’s starting dose.

Claims we could not support

No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.

Exact titration start: 0.25 mg semaglutide + 0.25 mg cagrilintide SubQ weekly, with food. No checked abstract stated this exact starting pair or the instruction to take it with a meal. Published abstracts reported target doses or different cagrilintide escalation steps.

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

Illustrative plasma concentration · 30 d

Half-life

~7 days

Both components

Peak · Tmax

1-3 days

Post-injection

Elimination

Weekly steady-state achieved after 4-5 weekly doses

Bioavailability

subQ ~75-80%

Duration of action

Weekly dosing maintains therapeutic exposure

Clearance

Hepatic and renal proteolysis

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.

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