Cagrilintide
Investigational long-acting amylin analog · once-weekly (SC) · not FDA-approved
Cagrilintide is an investigational long-acting amylin analog — a copy of amylin, a hormone the pancreas releases alongside insulin that signals fullness and slows the stomach. It is a different class from the GLP-1 drugs (Ozempic/Wegovy): amylin and GLP-1 work through separate but converging appetite pathways, which is the whole rationale for pairing them. It is NOT FDA-approved in any form. Only the combination product CagriSema (cagrilintide plus semaglutide) has been filed with the FDA (December 2025), and most of the impressive weight-loss data comes from that combination, not from cagrilintide alone: the phase 3 REDEFINE-1 trial reported about 22.7% mean weight loss for CagriSema versus about 11.8% for cagrilintide on its own. Honest framing matters here — this is an experimental drug with no real-world safety record, its strongest numbers depend on semaglutide, and its development path is contested (2026 reporting describes a head-to-head loss to tirzepatide).
The short version
Cagrilintide is a man-made, long-lasting copy of amylin. Amylin is a hormone your pancreas releases together with insulin after you eat; it tells your brain you are full, slows how fast your stomach empties, and dials down the post-meal sugar release from the liver. Natural amylin breaks down quickly and clumps easily, so cagrilintide is re-engineered to be stable and to stick to a blood protein (albumin), giving it a once-a-week action.
It is important to be clear about its status: cagrilintide is investigational. It is not approved by the FDA as a medicine, on its own or in combination. The only product based on it that has been filed for approval is CagriSema, which pairs cagrilintide with semaglutide (the drug in Ozempic and Wegovy).
Why combine the two? Amylin and GLP-1 are different hormones that reduce appetite through different brain pathways, so together they add up to more weight loss than either alone. That is why nearly all the eye-catching numbers you see for cagrilintide actually come from the combination — by itself it is meaningfully weaker.
Molecular identity
Specs
- Molecular weight
- 4409 g/mol
- Molecular formula
- C194H312N54O59S2
- Monoisotopic mass
- 4406.25 Da
- Amino acids
- 37-residue pramlintide-like backbone
- Structure / class
- Acylated long-acting amylin analog; 14E/17R, 25P/28P/29P, C-terminal Pro; C20 diacid via γ-Glu linkerPMID 34288673 (J Med Chem 2021)
- CAS / UNII
- 1415456-99-3 · AO43BIF1U8PubChem CID 171397054; FDA UNII
- Molecular target
- Amylin receptors (AMY1R/AMY3R) + calcitonin receptor (agonist)PMID 34288673
- Half-life
- ~7 days (~159–195 h; secondary PK aggregation)PMID 33894838 (phase 1b PK)Half-life curve →
- Regulatory status
- Investigational; not FDA-approved (only the CagriSema combination has an NDA on file)Novo Nordisk filing
Plain English
Mechanism
Cagrilintide is an amylin receptor agonist — "agonist" means a molecule that switches a receptor on, and amylin (also called islet amyloid polypeptide) is a hormone co-released with insulin from the pancreas. This is a different pathway from the GLP-1 drugs: GLP-1 is an incretin made in the gut, while amylin is made in the pancreas, and that distinction is the entire reason the two are combined.
It activates the amylin receptors known as AMY1R and AMY3R (these are calcitonin receptors paired with helper proteins called RAMP1 and RAMP3), and it also engages the calcitonin receptor itself. Animal work shows that removing RAMP1/RAMP3 abolishes its weight effect, confirming those receptors are essential to how it works.
It acts mainly in the brainstem — first in the area postrema (a satiety and nausea center that sits outside the blood–brain barrier), then through the nucleus of the solitary tract and the parabrachial nucleus, plus the hypothalamus. The practical result is increased satiety (feeling full) and slower gastric emptying, which cuts food intake. Interestingly, the research suggests sustained weight loss is partly independent of long-term appetite suppression, hinting at additional metabolic effects, and the trials report it tends to preserve lean mass while reducing fat.
Sources:PMID 40609154PMID 34288673
Why people reach for it
Potential benefits
Cagrilintide is the amylin half of the most talked-about combination in obesity research — here's what draws interest to it, with its investigational status front and center.
- A different appetite lever than the GLP-1 drugs — Its core appeal: amylin is a separate satiety hormone working through its own receptor, so it adds a brake the GLP-1 agonists don't have — the whole reason it's paired with them rather than swapped in.
- Additive weight loss when paired — In the Phase 3 REDEFINE-1 trial, the CagriSema combination (Semaglutide + cagrilintide) produced about 22.7% mean weight loss — meaningfully more than either component alone, the headline result the program is built on.
- Meaningful loss even on its own — As monotherapy it produced up to about 11.8% weight loss over 68 weeks — and in a Phase 2 head-to-head it edged out Liraglutide, so it carries real standalone signal.
- May spare more lean mass — The trials report amylin analogs tend to preserve lean mass while reducing fat better than GLP-1 alone — an appealing body-composition edge, though "tends to" is not a guarantee.
- A convenient once-weekly schedule — Its ~7-day half-life (from albumin binding) supports one injection a week, and it can ride on the same day as a weekly GLP-1 partner.
Sources:DOI 10.1056/NEJMoa2502081PMID 34798060PMID 33894838PMID 40609154
What draws interest to Cagrilintide, based on what its trials report and how it's used — not approved outcomes or medical claims. It is investigational, not FDA-approved in any form, and its strongest numbers depend on semaglutide.
Implied timing
Best time to dose
Implied best time
Anytime (consistent, weekly)
Cagrilintide is taken on one fixed day each week — the day you hold it matters, the hour does not.
- Its half-life is about 7 days, so blood levels stay broadly steady across the week — there is no daily peak to align with a clock. Picking one weekday and holding it is what keeps exposure even.
- Effects build over weeks: satiety deepens through the slow titration and weight loss accrues over months, so the timing of any single dose does not change the outcome — week-to-week consistency does.
- It is commonly run alongside Semaglutide in the CagriSema pairing, where both injections are usually given on the same day — so aligning cagrilintide's day with its GLP-1 partner is the practical convention.
- The main day-to-day variable is nausea, so many people pick a low-activity day for the dose so any transient queasiness doesn't collide with training.
No study establishes an ideal time of day for Cagrilintide — this is reasoned from its ~7-day half-life and how it's used in trials. The usual peptide-dosing default is the midday-to-evening window, but for a once-weekly agent the real lever is the same weekday each week, not the hour.
Sources:PMID 33894838
How to run it
Dosing & protocol
Cagrilintide is injected subcutaneously once weekly — the ~7-day half-life comes from the C20 fatty-diacid chain binding albumin in the blood, which makes weekly dosing practical. There is no approved dosing label; the anchor below is the 2.4 mg/week carried into the CagriSema Phase 3 program. The critical insight for this class: titrate slowly. The GI side effects (nausea, constipation) are dose-dependent and front-loaded; a gradual ramp is the only lever you control.
Investigational: no approved dose exists. All figures are trial doses (primarily the CagriSema Phase 2/3 program); this is NOT a prescription or a regulatory titration schedule. WADA: not explicitly named on the 2026 Prohibited List, but plausibly falls under S2 by class inference — confirm before competition.
Tiered / trial-anchored dose
No approved dose exists. The only credible anchor is the Phase 2/3 CagriSema trial dose.
- Starting / low dose:
- 0.3–0.6 mg SC once weekly — the lowest doses tested in the phase 2 monotherapy trial. Where most protocols begin, held for 4 weeks before escalating, to let GI side effects settle.
- Escalation ladder:
- Increase by ~0.3–0.6 mg every 4 weeks as tolerated. The phase 2 dose-finding range ran from 0.3 mg to 4.5 mg; the practical ceiling for most users is the 2.4 mg anchor.
- Target / trial dose:
- 2.4 mg SC once weekly — the dose carried into the REDEFINE-1 Phase 3 CagriSema trial and the FDA filing. As monotherapy this arm produced ~11.8% weight loss at 68 weeks; in CagriSema (with semaglutide 2.4 mg) it produced ~22.7%.
- Monotherapy vs combination:
- The headline numbers belong to CagriSema, not cagrilintide alone. Always check which arm a figure comes from before quoting it.
Subcutaneous administration
Weekly SC injection — site, rotation, and a small food-timing note are the actionable choices.
- Injection site:
- Abdomen (2–3 cm clear of the navel), outer thigh, or upper-arm fat. Rotate injection sites weekly so no single spot is repeatedly loaded — this prevents lipohypertrophy and maintains consistent absorption.
- Day and time of week:
- Pick one day per week and hold it. Consistency matters more than which day. Many users align it with a low-activity day so that any transient nausea does not hit a training session.
- Food window:
- Injecting after a light, low-fat meal reduces peak nausea during titration — gastric emptying is already slowed by the drug, so a heavy meal on injection day amplifies GI discomfort. Keep early doses in particular away from large high-fat meals.
Cycle / duration
Long-acting metabolic peptides are typically run in sustained courses, not short cycles — weight loss is cumulative and benefit tracks with duration.
- Minimum useful duration:
- 16–26 weeks. The phase 2 trial ran 26 weeks; meaningful weight loss trajectories in the phase 3 program extended to 68 weeks. Short cycles below 12 weeks produce limited metabolic effect.
- Ongoing maintenance:
- Weight loss with amylin analogs, like GLP-1s, is largely maintained only while the drug is active. Discontinuation in trials typically led to weight regain. A maintenance dose (commonly a lower weekly amount once target is reached) is the approach used in the trial setting.
- Washout:
- Given the ~7-day half-life, a 4-week period is sufficient to clear the compound. Recheck fasting glucose, lipids, and body composition at the end of a course to assess effect.
Reconstitution at a glance
The on-page calculator runs this live. Quick reference for the default 5 mg vial / 2 mL BAC water fill:
- Mixing:
- 5 mg vial + 2 mL bacteriostatic water = 2,500 mcg per mL. On a 100-unit (1 mL) insulin syringe: 300 mcg = 12 IU · 600 mcg = 24 IU · 1,200 mcg = 48 IU · 2,400 mcg = 96 IU.
- Dose unit conversion:
- Note: cagrilintide is dosed in mg in trials, not mcg. 2.4 mg = 2,400 mcg = 96 IU at this mix. Use the calculator for any vial size or dose.
Substrate the signal needs
Nutritional cofactor precision
Cagrilintide slows gastric emptying and crushes appetite — the two biggest trade-offs are GI side effects during titration and the risk of losing lean mass on a large caloric deficit. Every useful cofactor answers one of those two problems, or fills the micronutrient gaps that a much smaller food volume inevitably creates.
Reasoned from amylin physiology and weight-loss nutrition — not a cagrilintide supplement trial. Supplement doses are standard community ranges, not cagrilintide-specific findings.
MITIGATE nausea — Ginger + Vitamin B6
The two most-used GI comfort tools during amylin / GLP-1 titration.
- Ginger:
- 1–2 g standardized ginger extract (or 1–2 cups fresh ginger tea) 20–30 minutes before injection day's first meal. Ginger antagonizes the 5-HT3 receptor in the gut — the same receptor ondansetron (a prescription anti-nausea drug) targets. For the weeks of active titration, daily use is typical; taper once the stable dose is tolerated.
- Vitamin B6 (pyridoxine):
- 25–50 mg B6 daily. The ginger + B6 combination is the standard non-prescription anti-nausea stack; B6 is thought to lower prostaglandin-driven nausea signaling. Keep at the lower end — doses above 100 mg/day chronically carry peripheral neuropathy risk.
MITIGATE constipation — Magnesium + Fiber + Hydration
Slowed gastric emptying plus dramatically reduced food volume creates constipation in a large fraction of users. Manage it proactively rather than after onset.
- Magnesium glycinate or citrate:
- 300–400 mg elemental magnesium in the evening. Magnesium draws water into the colon, softening stool; the glycinate form avoids the loose-stool overshoot of magnesium oxide at the same dose. Start at 200 mg and titrate up over 1–2 weeks.
- Soluble fiber (psyllium):
- 5–10 g psyllium husk in 250–300 mL water once daily, at a different time than injection. Soluble fiber forms a gel that bulks and softens stool; it also feeds short-chain fatty acid–producing bacteria (butyrate), which supports the gut lining that slowed motility stresses.
- Hydration:
- Target at least 2.5–3 L water daily, more in hot weather or with exercise. Eating less means less water from food; constipation severity tracks directly with hydration status in this class.
MITIGATE electrolyte depletion — Sodium / Potassium / Magnesium
Eating far less plus any nausea or diarrhea episodes depletes electrolytes faster than most users expect.
- Sodium:
- Do not aggressively restrict sodium while on a GLP-1/amylin-class drug. Reduced food intake already drops sodium; add a small pinch of salt to water or meals if you notice fatigue, headaches, or light-headedness — these are hyponatremia warning signs.
- Potassium:
- Target potassium-rich foods (avocado, leafy greens, salmon) daily. If diet is very restricted, a low-dose potassium supplement (100–200 mg/day as potassium citrate) covers the gap; avoid high-dose single-dose supplementation.
- Magnesium:
- Covered by the constipation card above — one dose handles both jobs.
SUPPLY lean mass — Protein + Creatine + Resistance training
Amylin tends to preserve lean mass better than GLP-1 alone in trials — but 'tends to preserve' is not the same as 'automatically preserves.' A large caloric deficit without active defense loses muscle. This is the most important cofactor group.
- Protein:
- 1.6–2.0 g per kg of body weight per day (0.7–0.9 g per lb). With appetite suppressed, hitting this number requires deliberate protein-first meals: protein at every meal before carbohydrates or fat, using high-density sources (Greek yogurt, eggs, cottage cheese, lean meat, whey). The target applies to current body weight, not goal weight.
- Creatine monohydrate:
- 3–5 g daily, any time. Creatine does not add lean mass on its own, but it preserves muscle cell water content, reduces muscle protein breakdown markers, and improves resistance training output on a caloric deficit — all documented in weight-loss contexts. No loading phase required at 3–5 g/day.
- Resistance training:
- 2–4 sessions per week is the minimum to meaningfully counter muscle loss during a significant caloric deficit. Without the mechanical signal of resistance training, neither protein nor creatine can fully prevent lean mass erosion. This is the non-negotiable element — the supplements support it, they do not replace it.
SUPPLY micronutrient density — Multivitamin + Vitamin D
A much smaller food volume means micronutrient intake drops proportionally. A baseline safety net matters more on this class than on most.
- Broad-spectrum multivitamin:
- One daily comprehensive multivitamin with food. Priority nutrients to verify coverage: iron (if menstruating), B12 (especially if plant-based), zinc, folate. On a very low calorie intake, a multivitamin is not optional.
- Vitamin D3 + K2:
- 2,000–4,000 IU vitamin D3 with K2 (100 mcg MK-7) daily with a fat-containing meal. Vitamin D is fat-soluble and absorption tracks fat intake; on a reduced-fat diet, active supplementation is the reliable source. D3 supports immune function, muscle strength, and insulin sensitivity — all relevant on a metabolic compound.
Combinations + timing
Stacking notes + timing windows
Cagrilintide is an amylin analog. Its defining combination is with a GLP-1 agonist — two entirely different appetite pathways converging on the same outcome. Pairing amylin with more amylin would be redundant; every useful combination adds a lever cagrilintide does not have.
CagriSema is the one trial-tested combination in this entire family — cite it accordingly. All other pairings are reasoned from mechanism and community convention, not tested as combinations. Investigational compound throughout; no approved dose.
Cagrilintide + Semaglutide (CagriSema) — the defining combination
This is the only stack in this catalog with Phase 3 trial data behind it. Amylin and GLP-1 are different hormones acting through different brain circuits — the additive weight loss is mechanistically expected and trial-confirmed.
- Why it works:
- Amylin acts mainly in the brainstem area postrema (satiety + gastric braking); GLP-1 acts on hypothalamic and vagal circuits (insulin secretion + satiety via a different route). The two signals converge on appetite suppression without competing for the same receptor — true complementary mechanisms, not redundancy.
- The protocol:
- Cagrilintide 2.4 mg SC weekly + Semaglutide 2.4 mg SC weekly, co-titrated slowly. Both are escalated in parallel on the same weekly schedule — the trial started each at a low dose and escalated together to limit additive GI load. Do not rush to full dose on either.
- Outcome:
- REDEFINE-1 (n=3,417, 68 weeks): CagriSema −22.7% body weight (trial-product estimand) vs cagrilintide monotherapy −11.8% and semaglutide monotherapy −16.1%. The combination is meaningfully better than either alone. GI side effects are also additive (~79.6% incidence vs ~39.9% placebo) — slow titration is the most important protocol choice.
Cagrilintide + Tirzepatide (dual GIP/GLP-1 extension)
The same amylin-plus-incretin rationale applied to a dual incretin agonist. Tirzepatide covers both GIP and GLP-1; cagrilintide adds the amylin axis tirzepatide lacks.
- Why it works:
- Tirzepatide activates GIP and GLP-1 receptors simultaneously but has no amylin pathway activity. Adding an amylin analog adds a third distinct satiety mechanism — area postrema gastric braking — on top of the dual incretin signal. Active investigational direction, not yet a filed combination.
- The protocol:
- Cagrilintide (titrating from 0.3 mg to 2.4 mg SC weekly) alongside Tirzepatide at its own titration schedule (starting at 2.5 mg SC weekly, escalating to target dose). Both require their own slow ramps; GI tolerance is the rate-limiting factor. Not a combination with published safety data — approach with caution and slower escalation than either alone.
- Outcome:
- Theoretical maximum-breadth appetite-pathway coverage: GIP + GLP-1 + amylin. No head-to-head trial data yet; this is the investigational frontier of the drug class.
Cagrilintide + Creatine + GH secretagogue (lean mass defense)
On a large caloric deficit, protecting lean mass requires active intervention. This is not a weight-loss stack — it is the defensive layer that runs alongside whichever amylin or GLP-1 protocol is primary.
- Why it works:
- Cagrilintide suppresses appetite deeply; without a counter-signal, the body catabolizes muscle alongside fat. Creatine (3–5 g/day) reduces muscle protein breakdown markers and preserves training output on a deficit. A Ipamorelin or CJC-1295/Ipamorelin stack adds endogenous GH pulsatility, which has independent lean-mass-sparing and fat-oxidation effects through a different axis (GH/IGF-1 signaling), not competing with amylin pathways at all.
- The protocol:
- Creatine monohydrate 3–5 g daily (any time, with food or water). Ipamorelin 200–300 mcg SC at bedtime, 5-on/2-off weekly — the classic lean-phase schedule. Resistance training 3–4 days/week is the non-negotiable anchor; neither compound replaces the mechanical stimulus.
- Outcome:
- Leans the weight-loss composition toward fat loss and away from lean mass loss — the primary failure mode of aggressive caloric restriction via appetite suppression. The GH secretagogue adds an independent metabolic lever; the creatine protects training quality while in deficit.
Reconstitution math
Reconstitution calculator
Reconstitution calculator
Calculated for a 1 mL U-100 insulin syringe (100 units/mL).
Units per dose
96
Draw to this mark on a U-100 syringe
- Volume per dose
- 0.96 mL
- Doses per vial
- 2
- Concentration
- 2.5 mg/mL
One vial lasts
- Daily
- 2 days
- Every other day
- 4 days
- 5×/week
- 2 days
- Large draw (96 units). Double-check the vial size and dose — a mcg/mg mix-up produces values like this.
Research use only. Not for human consumption. Outputs are reference values based on research literature — verify all measurements independently.
From the studies
Side effects from research
All safety information for cagrilintide comes from clinical trials only — there is no post-approval or long-term real-world surveillance, because the drug is not approved. That gap is itself a key caveat: rare events and long-term cardiovascular safety are simply not yet known.
The predominant side effects are gastrointestinal: nausea, constipation, and diarrhea lead the adverse-event lists across all trials. In the phase 2 monotherapy study, nausea occurred in roughly 20–47% of cagrilintide arms versus about 18% on placebo. In the CagriSema combination the GI burden is higher still — around 79.6% in REDEFINE-1 versus 39.9% on placebo.
A dedicated thorough-QT study found no clinically relevant effect on the heart's QT interval at the maximum 4.5 mg dose. Standard incretin- and amylin-class concerns apply by analogy, but because the drug is investigational, the honest position is that its full safety profile is not yet established.
As reported in literature
Research dosing ranges
These are doses tested in published clinical trials, shown separately so the trial evidence is never mistaken for a recommended or approved regimen. All were given subcutaneously (under the skin) once weekly under medical supervision in investigational studies. Note which rows are cagrilintide alone versus the CagriSema combination — the headline numbers depend on it. REDEFINE-1 weight loss is the trial-product estimand; a treatment-policy estimand (~−20.4%) also exists.
| Dose | Route | Model | Outcome | Sources: |
|---|---|---|---|---|
| 0.16–4.5 mg | SC weekly (20 wk) | Human (Phase 1b, + semaglutide 2.4 mg, no diabetes, single center) | Combination −17.1% at top dose vs semaglutide alone; well tolerated | PMID 33894838 |
| 0.3–4.5 mg | SC weekly (26 wk) | Human (Phase 2 monotherapy, n=706, obesity, no diabetes) | Weight −6.0% to −10.8% vs −3.0% placebo; 4.5 mg −10.8% vs liraglutide −9.0% (p=0.03) | PMID 34798060 |
| 2.4 mg | SC weekly | Human (CagriSema Phase 2, type 2 diabetes) | CagriSema −15.6% vs cagrilintide −8.1% vs semaglutide −5.1% | PMID 37364590 |
| 2.4 mg | SC weekly (68 wk) | Human (REDEFINE-1 Phase 3, n=3,417, obesity, no diabetes) | CagriSema −22.7% vs cagrilintide −11.8%, semaglutide −16.1%, placebo −2.3% (trial-product estimand) | DOI 10.1056/NEJMoa2502081 |
| up to 4.5 mg | SC weekly | Human (Thorough QT study, n=105 healthy) | No clinically relevant QTcF prolongation at 4.5 mg | PMID 39279639 |
Quick answers
Frequently asked
What is cagrilintide?
It is an investigational long-acting amylin analog — a stable copy of amylin, a pancreatic hormone that signals fullness and slows the stomach. It is given as a once-weekly injection in trials and is being developed mainly in combination with semaglutide (as CagriSema). It is a different drug class from the GLP-1 agonists.
Is cagrilintide FDA-approved?
No. As of 2026 it is not approved in any form. Only the combination product CagriSema (cagrilintide plus semaglutide) has been filed with the FDA, in December 2025, with a decision expected late 2026. Cagrilintide on its own has no disclosed regulatory path.
How is it different from Ozempic or Wegovy?
Those are GLP-1 agonists, which mimic an incretin hormone made in the gut. Cagrilintide mimics amylin, a hormone made in the pancreas, working through a separate appetite pathway. Because the two pathways converge, combining an amylin analog with a GLP-1 agonist produces more weight loss than either alone — which is the rationale for CagriSema.
How much weight loss does cagrilintide produce?
On its own, up to about 10.8% over 26 weeks in a phase 2 trial. The larger figures — about 17% in early combination work and 22.7% in the phase 3 REDEFINE-1 trial — all come from combining it with semaglutide, not from cagrilintide alone.
Is cagrilintide banned in sport?
It is not explicitly named on the 2026 WADA Prohibited List in the sources reviewed. As a peptide hormone it would plausibly fall under WADA Category S2 (peptide hormones and mimetics), which is banned at all times — but that is an inference from its class, not a confirmed listing, so it should not be stated as settled.
Why is its development described as contested?
Although REDEFINE-1 showed strong weight loss, 2026 reporting described the CagriSema program as underperforming some expectations and losing a head-to-head comparison to tirzepatide (Zepbound). The drug remains under active, contested development, so its competitive positioning is not settled.
Primary sources
References
- PubChem CID 171397054PubChem CID 171397054 (Cagrilintide)
- PMID 34288673Kruse et al., J Med Chem 2021 (development of cagrilintide)
- PMID 40609154Brain amylin receptors 1 and 3 mediate cagrilintide weight loss (2025)
- PMID 33894838Enebo et al., Lancet 2021 (phase 1b cagrilintide + semaglutide)
- PMID 34798060Lau et al., Lancet 2021 (phase 2 cagrilintide monotherapy)
- PMID 37364590Frias et al., Lancet 2023 (CagriSema phase 2, type 2 diabetes)
- DOI 10.1056/NEJMoa2502081REDEFINE-1, NEJM 2025 (CagriSema phase 3)
- PMID 39279639Thorough QT study, cagrilintide up to 4.5 mg (2024)
- WADA 2026WADA 2026 Prohibited List (cagrilintide not named; S2 by class inference)
Research use only · Not medical advice · Updated 2026-06-01