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Cagrilintide37 residuesKCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTYEach bubble = one amino acid. Size = residue mass. Color = chemical class.Also known as: NN9838, AM833
REDEFINE 1 enrolled 3,416 adults and settled the question: amylin receptor activation produces real weight loss. Cagrilintide (NN9838) is a long-acting amylin analog dosed once per week by subcutaneous injection. At 2.4 mg, monotherapy produced 11.5% mean body weight loss at 68 weeks. Paired with semaglutide as CagriSema, that jumped to 20.4%. The mechanism is entirely separate from GLP-1 signaling. Novo Nordisk filed the CagriSema NDA in December 2025 with a PDUFA target around October 2026. No standalone cagrilintide application exists; all current supply is research-grade and unregulated.
20.4% body weight gone at 68 weeks. That was the CagriSema arm of REDEFINE 1 [1], a Phase 3 trial of 3,416 adults with overweight or obesity. Cagrilintide (NN9838) is a long-acting acylated amylin analog. It binds AMY1, AMY2, AMY3, and calcitonin receptors in the area postrema and hypothalamus. Where GLP-1 drugs suppress homeostatic hunger, cagrilintide targets hedonic hunger: food-cue reactivity, cravings, reward-driven eating. The two pathways are additive, which is why the combination outperforms either agent alone. Fatty acid conjugation gives cagrilintide a 159 to 195 hour half-life (Enebo et al., Lancet 2021)[2]. One injection per week. Compare that to pramlintide, the only FDA-approved amylin analog, which requires three injections per day for roughly 2 to 3 kg total weight loss. The Phase 2 dose-finding trial (Lau et al., Lancet 2021)[3] showed the 4.5 mg dose outperformed liraglutide 3.0 mg. REDEFINE 1 confirmed monotherapy at 2.4 mg produces 11.5 to 11.8% weight loss. CagriSema reaches 20.4% (intent-to-treat) and 22.7% (on-treatment estimand) at 68 weeks. In the REDEFINE 2 T2D cohort [4], CagriSema delivered 13.7% weight loss with 73.5% of patients reaching HbA1c at or below 6.5%. Novo Nordisk filed the CagriSema NDA in December 2025. No standalone cagrilintide approval exists. All current supply is research-grade, with purity inconsistency flagged as the top community complaint.
Amylin is a 37-amino-acid hormone co-secreted with insulin from pancreatic beta cells after meals. It slows gastric emptying, suppresses postprandial glucagon, and sends satiety signals to the brainstem. Cagrilintide mimics this hormone but lasts roughly 100 times longer in circulation thanks to fatty acid acylation (a C18 diacid attached to a lysine residue). The primary targets are amylin receptors (AMY1, AMY2, AMY3) and calcitonin receptors concentrated in the area postrema. Activation there reduces hedonic hunger, the kind driven by food cues and reward pathways rather than caloric need. GLP-1 agonists suppress homeostatic hunger through hypothalamic circuits. The two mechanisms operate on parallel but distinct neurocircuitry. That separation is why CagriSema produces supra-additive weight loss. REDEFINE 1 showed 20.4% for the combination versus 14.9% for semaglutide alone and 11.5% for cagrilintide alone [1]. The arithmetic sum would predict roughly 26%; the actual 20.4% suggests some ceiling effect on shared downstream pathways like gastric emptying inhibition. Cagrilintide also suppresses postprandial glucagon secretion. In T2D patients (REDEFINE 2)[4], CagriSema improved HbA1c alongside weight, with 73.5% reaching the 6.5% threshold.
CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg/week) achieves ~20.4% mean body weight loss at 68 weeks in adults with overweight/obesity (REDEFINE 1, NEJM 2025). Cagrilintide monotherapy achieves ~11.5–11.8% at the same timepoint. In T2D patients (REDEFINE 2), CagriSema delivers ~13.7% weight loss with 73.5% achieving HbA1c ≤6.5%. Combination is supra-additive vs. either agent alone.
REDEFINE 1 Phase 3 RCT, NEJM June 2025 (PMID 40544433); n=3416 non-diabetic adults; 68-week follow-up; 1:1:1:1 randomization (CagriSema vs cagrilintide vs semaglutide vs placebo)
CagriSema NDA under FDA review (submitted Dec 18, 2025; PDUFA ~Oct 2026); no post-market pharmacovigilance; GI AEs in 72.5% of CagriSema participants; calcitonin receptor MTC signal unconfirmed in humans but mechanistically stronger than GLP-1 class; no data beyond 68 weeks; no standalone cagrilintide NDA filed
Viewed as the most promising non-GLP-1 weight mechanism for breaking GLP-1 plateaus or maximizing total weight loss. CagriSema equivalent stack is the dominant use case; monotherapy seen as a lower-priority option.
Science (REDEFINE 1 & 2) validates CagriSema combo and the 0.25 mg starting dose with controlled titration. Community has adopted CagriSema equivalent stacking but the 0.5 mg starting dose error persists widely, and GI management guidance is less structured than the trial protocol. Monotherapy is well-supported by Phase 3 data but underused in community due to lower weight loss ceiling vs. combo.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 250mcg | Weekly |
| Moderate | 1mg | Weekly |
| Aggressive | 2,400mcg | Weekly |
Most common mistake: starting at 0.5 mg instead of 0.25 mg. The seven-day half-life means each dose stacks on the previous one during accumulation. Starting at double the validated initiation dose makes the first month of GI effects far worse than necessary. Reconstitution math for a 5 mg vial: add 2 mL bacteriostatic water. That gives you 2,500 mcg per mL. On a U-100 insulin syringe, each IU mark equals 25 mcg. So 0.25 mg (250 mcg) is 10 IU; 0.5 mg is 20 IU; 1.0 mg is 40 IU; 1.7 mg is 68 IU; 2.4 mg is 96 IU. One 5 mg vial covers roughly the first two titration steps (about 3 mg total across 8 weeks). Use bacteriostatic water, not acetic acid. Amylin peptides form fibrils at low pH. If the reconstituted solution looks cloudy or shows particles, discard the vial. Refrigerate at 2 to 8 degrees C, protect from light and agitation, use within 4 weeks. If you're also running semaglutide, inject at separate anatomical sites. Separate days let you isolate which peptide is causing any GI issues.
Designed as continuous therapy. No cycling needed due to sustained amylin receptor responsiveness. Discontinuation leads to weight regain, so ongoing use is expected.
Cagrilintide is designed as continuous long-term therapy analogous to GLP-1 agonists. Amylin receptor responsiveness is maintained without tachyphylaxis at therapeutic doses: receptor desensitization is not a recognized mechanism of action loss. Discontinuation leads to rapid weight regain as appetite regulation reverts to baseline. The concept of "cycling" does not apply; ongoing use is the clinical and community standard.
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Expected: ~11.5–11.8% mean body weight loss at 68 weeks (REDEFINE 1 cagrilintide monotherapy arm)
Monitor: Monthly weight. Track GI symptoms during titration steps. Calcitonin/thyroid function at baseline if personal or family history of thyroid disease or MTC.
Insert the needle at the side of the vial and let the water run down the glass. Swirl gently; never shake. The solution should be clear and colorless.
At 2,500 mcg/mL concentration: 0.25 mg equals 10 units, 0.5 mg equals 20 units, 1.0 mg equals 40 units, 1.7 mg equals 68 units, 2.4 mg equals 96 units.
Recommended sites: abdomen (at least 2 inches from the navel), front of the thigh, or back of the upper arm.
Pinch a fold of skin and insert a 29 to 31 gauge needle at 45 to 90 degrees. Inject slowly. Hold for 5 to 10 seconds before withdrawing.
Morning is preferred but not required.
Follow the REDEFINE titration: 0.25 mg (10 IU) weeks 1 to 4, then 0.5 mg (20 IU) weeks 5 to 8, then 1.0 mg (40 IU) weeks 9 to 12, then 1.7 mg (68 IU) weeks 13 to 16, then 2.4 mg (96 IU) from week 17 onward. Escalate only after GI side effects from the current step have settled.
If combining with semaglutide, inject at a separate anatomical site. Separate days help you identify which peptide causes any side effects.
Use within 4 weeks. Discard if cloudy or discolored.
CagriSema equivalent: amylin hedonic suppression + GLP-1 homeostatic suppression; supra-additive weight loss (~20.4% combo vs 14.9% semaglutide alone). Best-studied cagrilintide combination with Phase 3 clinical data.
Cagrilintide 0.25→2.4 mg/week titration + semaglutide 2.4 mg/week (REDEFINE protocol)
Off-label community stack (CagriTirze): amylin pathway + dual GLP-1/GIP; theoretically additive via distinct receptor systems. No clinical trial data; increasing community interest post-REDEFINE.
Cagrilintide 0.25→2.4 mg/week + tirzepatide at tolerated dose; extra GI caution required
Amylin suppresses postprandial glucagon; combined with insulin or secretagogues raises hypoglycemia risk, especially at higher cagrilintide doses.
Directly antagonize cagrilintide's gastric emptying inhibition mechanism; pharmacodynamic opposition undermines therapeutic effect.
Pricing updated 2026-04-09
Calcitonin receptor activation carries a theoretical medullary thyroid carcinoma (MTC) concern that warrants attention first. Cagrilintide directly binds calcitonin receptors, making the mechanistic basis for this risk stronger than the indirect C-cell stimulation seen with GLP-1 drugs. No confirmed human MTC cases have appeared in clinical trials so far. Novo Nordisk lists personal or family history of MTC and MEN2 as contraindications. Baseline serum calcitonin testing is precautionary for anyone with thyroid disease history. GI side effects are the most common clinical issue. In REDEFINE 1 [1], 72.5% of CagriSema participants reported at least one GI adverse event versus 34.4% on placebo. Nausea tops the list. Diarrhea, vomiting, and decreased appetite follow. These effects peak during titration (weeks 1 through 16) and improve for most people at maintenance dose. The starting-dose error matters. Community forums show a persistent pattern of users beginning at 0.5 mg instead of the REDEFINE-validated 0.25 mg initiation dose. Cagrilintide has a seven-day half-life; each weekly dose stacks on the previous one during accumulation. Starting at double the recommended dose amplifies GI burden across the first month disproportionately. Vomiting becomes a particular concern when cagrilintide is added on top of an existing GLP-1 at full dose. Both agents slow gastric emptying. Without reducing the GLP-1 temporarily, the additive effect can trigger severe nausea and vomiting that pushes people off the protocol entirely. Injection site reactions (redness, mild swelling, itching) occur at typical rates for subcutaneous peptides. Rotating between abdomen, thigh, and upper arm reduces recurrence. Hypoglycemia risk rises when cagrilintide is combined with insulin or sulfonylureas. Amylin suppresses postprandial glucagon; layering that on top of exogenous insulin can push blood glucose dangerously low. Blood glucose monitoring is recommended for anyone on concurrent diabetes medications. Oral medications may absorb more slowly because cagrilintide delays gastric emptying. This matters for time-sensitive drugs like oral contraceptives and levothyroxine. Research-grade purity is its own safety concern. No regulatory manufacturing standards apply to currently available cagrilintide. Batch inconsistency is the number one community complaint. Amylin-class peptides are amyloidogenic; incorrect reconstitution pH promotes fibril formation. Use bacteriostatic water at pH 5.5 to 6.5 and avoid acetic acid solutions. When to stop: persistent severe GI symptoms that don't resolve with dose reduction; any signs of thyroid nodules or neck swelling (check calcitonin); confirmed or suspected pregnancy. If combining with insulin, any episode of symptomatic hypoglycemia needs immediate medical evaluation.
Verify Cagrilintide dosing and safety with a second opinion
No FDA-approved standalone form exists; all available cagrilintide is research-grade with no regulatory manufacturing standards. Significant batch-to-batch purity inconsistency is the #1 community complaint. Amyloidogenic potential (amylin peptide class) requires specific reconstitution pH to avoid fibril formation; incorrect solvent can render product partially inactive or create particulate matter.
| Test | When | Target |
|---|---|---|
| Body weight | Weekly during titration (weeks 1–16); monthly at maintenance | — |
| Fasting blood glucose / HbA1c | Baseline; every 3 months | FBG 70–99 mg/dL; HbA1c <5.7% (normal range) |
| Serum calcitonin | Baseline; at 6 months; if thyroid nodules or neck symptoms develop | <10 pg/mL (normal) |
| GI symptom log | Weekly during titration (weeks 1–16) | — |
| Lipid panel | Baseline; 3–6 months into maintenance | — |
Primary efficacy endpoint; tracks response to dose escalation steps
Amylin suppresses postprandial glucagon; increased hypoglycemia risk when combined with insulin or sulfonylureas; HbA1c confirms metabolic benefit in T2D or pre-diabetic patients
Cagrilintide directly activates calcitonin receptors: mechanistically stronger MTC signal than GLP-1 class (which acts indirectly via C-cell stimulation). No confirmed human cases; still precautionary per contraindication profile.
Dose-limiting nausea/vomiting is most common protocol failure cause; early tracking guides titration pace and identifies need to slow escalation
Weight loss typically improves lipid profile; confirms metabolic benefit alongside weight endpoints
Titration phase. Mild appetite reduction may begin. Nausea is most common during this period. Body adapts to amylin receptor activation.
Appetite suppression becomes noticeable. Early weight loss of 2-4%. GI side effects typically decrease as the body adjusts to dose escalation.
Steady weight loss continues. Phase 2 data showed ~6-9% body weight reduction at moderate doses by this point. Cravings and portion sizes decrease.
Full therapeutic dose. Monotherapy trials showed ~10.8% mean weight loss at 2.4mg. Metabolic markers improve. Weight loss rate stabilizes.
Continued maintenance of weight loss. In the REDEFINE 1 trial, cagrilintide monotherapy achieved ~11.8% weight loss at 68 weeks. Ongoing treatment is needed to sustain results.
Weeks 1 to 4 (0.25 mg), Titration Initiation: Plasma levels build gradually toward steady-state during the first month. Amylin receptor engagement begins at the area postrema and hypothalamus. Most people notice mild appetite reduction, particularly earlier satiety at meals. Nausea is the most common side effect at this step and is typically manageable at 0.25 mg. Injection site reactions can occur but usually resolve quickly. Don't expect visible weight change yet. Weeks 5 to 16 (0.5 to 1.7 mg), Escalation Phase: Appetite suppression strengthens with each dose increase across this 12-week window. Weight loss of 2 to 5% is common. Cravings drop noticeably, especially hedonic eating like snacking and food-reward behavior. GI side effects tend to ease for most users by weeks 9 to 12 as tolerance builds through the multi-step escalation. Escalate each four-week step only after the current dose feels settled. Weeks 17 to 32 (2.4 mg), Full Dose Established: Steady-state at the maximum maintenance dose. Weight loss continues at a steady pace. Metabolic markers (fasting glucose, lipids) start improving. Glucagon suppression peaks at postprandial windows. Monotherapy users may begin sensing plateau sensitivity around this phase; CagriSema users report a continued downward trajectory. GI side effects have mostly resolved. Weeks 33 to 68 (2.4 mg maintenance), Maintenance Plateau: Monotherapy reaches 11.5 to 11.8% mean body weight loss by week 68 (REDEFINE 1). CagriSema hits 20.4%. Weight loss rate slows as the body stabilizes at a new metabolic set-point. Most users report continued satisfaction with appetite control even as the scale moves less dramatically. Discontinuation, Weight Regain: Appetite returns to pre-treatment levels within 1 to 2 weeks of stopping. Measurable weight rebound follows within 2 to 4 weeks. The pattern mirrors GLP-1 discontinuation. Community consensus is direct: continuous use is required to sustain results. This is not a compound you cycle.
Gradual plasma accumulation toward steady-state. Amylin receptor engagement begins at area postrema and hypothalamus. Minimal weight loss expected at this stage.
Mild appetite reduction and early satiety, especially at meals. Nausea is most common: typically manageable at 0.25 mg. Most tolerate initiation dose well.
Appetite suppression strengthens progressively. Early weight loss 2–5%. GI side effects typically decrease as tolerance develops during multi-step escalation. Steady-state approached each step.
Noticeable reduction in food cravings, especially hedonic eating (snacking, food reward). Weight loss accelerates. GI side effects ease for most by weeks 9–12.
Steady-state at maximum maintenance dose. Continued weight loss and metabolic marker improvements (fasting glucose, lipids). Glucagon suppression at postprandial peak.
Consistent weekly weight loss. Cravings substantially reduced. Monotherapy users may begin to notice plateau sensitivity around this phase; CagriSema users report continued trajectory.
~11.5–11.8% mean body weight loss at 68 weeks for monotherapy; ~20.4% for CagriSema. Weight loss rate decelerates as new set-point established.
Monotherapy users report weight loss slowdown; most satisfied with appetite control maintenance. CagriSema users report continued loss through week 68.
Weight regain expected on cessation: amylin receptor activation no longer counteracting baseline appetite drive. Pattern mirrors GLP-1 discontinuation.
Significant appetite return and weight rebound reported within 2–4 weeks of stopping. Community consensus: continuous use required to sustain results.
Source: Phase 1b PK study (Enebo et al. Lancet 2021, PMID 33894838); t½ 159-195h (~7.3 days)
Loading the interactive decay curve.
Cagrilintide has no standalone FDA approval. Novo Nordisk submitted the CagriSema combination NDA (cagrilintide 2.4 mg plus semaglutide 2.4 mg) on December 18, 2025. The PDUFA target date falls around October 2026. If approved, only the fixed-dose combination pen would be commercially available. All currently available cagrilintide is research-grade, manufactured without FDA or EMA oversight. Quality varies between vendors, and no compounding pharmacy framework covers this peptide yet. Third-party HPLC certificates of analysis from independent labs (not vendor self-testing) are the best purity verification currently available. Cagrilintide is not a controlled substance. WADA has not formally addressed amylin analogs, but athletes subject to anti-doping testing should confirm status with their governing body before use. This content is for informational and educational purposes only. Nothing on Peptide Schedule constitutes medical advice. Consult a licensed healthcare provider before using any research compound.
Peptide Schedule Research TeamReviewed Apr 20267 Citations
