📚 Wiki Weight Loss & Metabolic CagriSema

CagriSema

◉ Phase III (Novo Nordisk)
Cagrilintide + Semaglutide Combination (2.4 mg / 2.4 mg)
Also known as: CagriSema 2.4, REDEFINE-1 protocol, Cagrilintide-Semaglutide
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Quick Summary

9%) and representing one of the strongest obesity pharmacotherapy results in clinical history. The combination works through complementary mechanisms: GLP-1 suppresses appetite centrally while amylin slows gastric emptying and promotes satiety signaling.

Metabolic & Mitochondrial Phase III
CagriSema is the research name for the combination of cagrilintide (an amylin/" class="wiki-internal-link">amylin analog) and semaglutide (a GLP-1 receptor agonist), both at 2.4 mg weekly. Developed by Novo Nordisk, the Phase III REDEFINE-1 trial showed ~22.7% mean body weight reduction at 68 weeks, exceeding semaglutide alone (~14.9%) and representing one of the strongest obesity pharmacotherapy results in clinical history. The combination works through complementary mechanisms: GLP-1 suppresses appetite centrally while amylin slows gastric emptying and promotes satiety signaling.
Storage Stability
Lyophilized
6–12 months (2–8°C)
Reconstituted
~30 days (2–8°C)
Room temp
Avoid

Mechanism of Action

GLP-1 Component (Semaglutide)

Semaglutide activates GLP-1 receptors in the hypothalamus, reducing hunger signals and increasing satiety. It also slows gastric emptying and reduces glucagon secretion, improving glycemic control.

Amylin Component (Cagrilintide)

Cagrilintide is a long-acting amylin/" class="wiki-internal-link">amylin analog that activates amylin receptors in the brainstem, independently reducing food intake and body weight. Amylin also modulates gastric emptying and glucagon secretion through mechanisms distinct from GLP-1.

Complementary Dual Pathway

The combination achieves greater weight loss than either component alone because the two peptides act on different receptor systems and brain regions. There is no pharmacodynamic overlap, the effects are additive, not redundant.

Research Summary

REDEFINE-1 Phase III Trial

In 3,417 adults with obesity (no diabetes), once-weekly CagriSema 2.4/2.4 mg for 68 weeks produced 22.7% mean body weight loss vs. 2.3% with placebo. This exceeds the ~14.9% seen with semaglutide 2.4 mg alone in the STEP-1 trial.

Responder Rates

~75% of CagriSema participants lost ≥15% body weight; ~40% lost ≥25%. These responder rates are substantially higher than single-agent GLP-1 therapies.

Safety Profile

GI side effects (nausea, vomiting, diarrhea) were the primary adverse events, consistent with the GLP-1 component. No new safety signals beyond what is known for semaglutide.

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Research Protocols

Titration Schedule

Both components are titrated upward over 16 weeks to reach the 2.4/2.4 mg maintenance dose. Rapid titration increases GI side effects.

Injection

Subcutaneous injection once weekly, same day each week. Rotate injection sites (abdomen, thigh, upper arm).

Note

CagriSema is not commercially available as of mid-2026. Research access requires sourcing each component separately and combining per protocol.

Storage & Handling

Store both components at 2–8°C. Do not freeze. Both are peptide solutions, protect from light and heat. Can be held at room temperature (<30°C) for up to 28 days once in use (per semaglutide labeling; confirm for cagrilintide per source).


References

  • [1]Novo Nordisk. "REDEFINE 1: CagriSema phase 3 trial results." NEJM, 2025.
  • [2]Lau J, et al. "Discovery of cagrilintide, a long-acting amylin analog." J Med Chem, 2021.
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Data Sources & External References
Source: peer-reviewed literature  ·  Domain: ascendpeptide.org
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