10.8% weight loss at 4.5 mg over 26 weeks (monotherapy) [1]
Phase 2 randomised, double-blind, placebo- and active-controlled dose-finding trial. Dose-ordered effect across 0.3–4.5 mg arms; the 4.5 mg arm outperformed liraglutide 3.0 mg.
PrecisePep/Peptide Library/Cagrilintide
Metabolic & Adipose Regulation
Cagrilintide
AM833 · Cagri · long-acting amylin analogue
A once-weekly amylin and calcitonin receptor agonist that works on satiety circuits incretins do not touch — which is precisely why it is being developed as a partner molecule rather than a solo drug.
00 Overview
Amylin is the other pancreatic beta-cell hormone. It is co-secreted with insulin and signals meal termination through the area postrema — a hindbrain satiety pathway anatomically and pharmacologically distinct from the GLP-1 route. Native amylin is useless as a drug: it aggregates, and its half-life is minutes. Cagrilintide is the engineered answer, an acylated analogue with a half-life long enough for weekly dosing and non-selective activity across amylin and calcitonin receptors.
As monotherapy in the phase 2 dose-finding trial, once-weekly cagrilintide produced roughly 10.8% weight loss at 4.5 mg over 26 weeks, versus 3.0% on placebo and 9.4% on liraglutide 3.0 mg.[1] Respectable — but the reason the molecule matters is combination. Because it acts on a separate satiety pathway, adding it to a GLP-1 agonist is additive rather than redundant, which is the entire premise of CagriSema.[2][3]
In the research-chemical market cagrilintide is almost never used alone. It appears as the junior partner to retatrutide or semaglutide, at doses well below those trialled, on the stated logic that a small amount of amylin agonism buys disproportionate appetite control and therefore permits a lower — and better tolerated — dose of the incretin.
// Mechanism of action
Amylin receptor agonism. Amylin receptors are calcitonin receptors dimerised with receptor activity-modifying proteins (RAMP1–3). Agonism in the area postrema and nucleus tractus solitarius produces satiation — the signal that a meal is finished — and slows gastric emptying. Critically, this is meal-termination signalling, not the appetite-and-reward suppression GLP-1 produces. The two act on different neurons and their effects add.
Calcitonin receptor agonism. Cagrilintide is deliberately non-selective and also activates the calcitonin receptor directly. This is thought to contribute additional and more durable weight effect, and it is also the source of the theoretical bone-turnover questions attached to the molecule.
Leptin re-sensitisation. Amylin agonism has been shown in pre-clinical work to restore leptin responsiveness in diet-induced obesity — one of the more interesting mechanistic claims in the class, and the historical basis for combination amylin/leptin programmes.
Why the combination is more than additive arithmetic. GLP-1 agonism reduces hunger; amylin agonism accelerates fullness. Suppressing intake from both ends is why CagriSema was designed as a fixed-dose combination rather than a dose escalation of either component.
01 Reported benefits
Effects that have been reported. A study-tier entry means a result was published — not that the effect is established, reproducible, or transferable from a rodent to a person.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Additive weight effect combined with semaglutide [2]
Phase 1b multiple-dose work established that cagrilintide co-administered with semaglutide 2.4 mg is tolerable and produces greater weight reduction than semaglutide alone — the finding that launched the CagriSema programme.
Phase 3 combination results (CagriSema, REDEFINE programme) [3][4]
The fixed-dose combination has been evaluated in a large phase 3 programme in obesity and in type 2 diabetes, producing weight reductions substantially exceeding semaglutide alone.
Nausea attenuates over time [1]
Gastrointestinal adverse events in the phase 2 trial were mostly mild to moderate and declined with continued exposure — a tolerability profile that is part of why it works as a combination partner.
Improved glycaemic parameters in the diabetes programme [4]
In type 2 diabetes, amylin analogue co-administration contributes to postprandial glucose control through slowed gastric emptying and glucagon suppression.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Preferential preservation of lean mass
A frequently repeated claim that amylin-driven loss is more fat-selective than incretin-driven loss. Body-composition sub-study data in the combination programme is the place to test it; treat it as an open hypothesis rather than an established advantage.
Reduced hedonic and binge-type eating [5]
Amylin signalling influences meal size and meal termination, and pre-clinical work links amylin pathways to reward-driven feeding. Extrapolation to clinical binge-eating outcomes is untested.
Lower incretin dose requirement, therefore fewer incretin side effects
The dose-sparing argument is the core rationale for community use of cagrilintide. It follows from additivity but has not been formally studied as a dose-reduction strategy for retatrutide specifically.
PCOS — weight-mediated only
Amylin agonism produces satiety and weight loss, and weight loss improves PCOS. The route runs entirely through weight rather than through a direct effect on insulin signalling, which makes it a longer chain than the incretin case — and the randomised PCOS evidence is for GLP-1 receptor agonists, a different class acting on a different receptor.
Leptin re-sensitisation as an anti-plateau mechanism [5]
Pre-clinical amylin work supports restored leptin sensitivity in diet-induced obesity. Whether this translates into resistance to the weight-loss plateau in humans is unresolved.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Strong early satiety at 0.5–1 mg weekly
The characteristic community report is a sharply reduced meal size — feeling full quickly rather than never feeling hungry. This maps precisely onto the meal-termination mechanism and is one of the more mechanistically coherent anecdotal reports on this site.
Allows a lower retatrutide dose for the same appetite control
The single most cited reason for community use. Uncontrolled, but consistent across reports.
Smoother appetite curve than GLP-1 alone
Users describe less of the "wave" of appetite return late in the dosing week. Consistent with the long half-life; unmeasured.
Less "food noise" reduction than expected
A useful counter-report: some users find cagrilintide reduces how much they eat without reducing how much they think about food, which is exactly what the mechanism predicts and what distinguishes it from GLP-1 agonism.
02 Adverse effects & risks
Adverse effects, contraindications and unknowns. The grey-market tier is where under-reporting is worst: uncontrolled use produces no systematic safety surveillance at all, so absence of a reported harm is not evidence of safety.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Gastrointestinal adverse events [1]
Nausea, vomiting, constipation and dyspepsia were the most common adverse events, dose-dependent, mostly mild to moderate, and declining with continued exposure.
Injection-site reactions [1]
Reported at rates typical for acylated subcutaneous peptides.
Additive GI burden in combination [2][3]
Combining cagrilintide with a GLP-1 agonist increases total gastrointestinal adverse-event rates relative to either alone. The combination is better tolerated than an equivalent dose escalation of the incretin, which is not the same as being well tolerated.
Immunogenicity and anti-drug antibodies [6]
Amylin analogues have a history here — pramlintide, the first approved amylin analogue, is meaningfully immunogenic. Analogue-specific antibody formation is a standard monitored endpoint in the cagrilintide programme.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Hypoglycaemia risk with insulin or secretagogues [6]
Pramlintide carries a boxed warning for severe insulin-induced hypoglycaemia and mandates insulin dose reduction on initiation. Anyone extrapolating amylin pharmacology to an insulin-treated context should start from that warning.
Bone-turnover effects from calcitonin receptor agonism
Calcitonin inhibits osteoclast activity. Chronic non-selective calcitonin receptor agonism has theoretical bone-remodelling consequences, and long-term calcitonin exposure has historically carried a malignancy signal in regulatory review. Unresolved for cagrilintide.
Delayed gastric emptying and oral drug absorption
Slowed emptying alters absorption kinetics of concomitant oral medication — clinically relevant for narrow-therapeutic-index drugs.
Altered levothyroxine absorption — additive in a stack
Amylin agonism slows gastric emptying in its own right, so this is not an interaction cagrilintide avoids by being a different class — it contributes to it. In a reta+cagri or sema+cagri stack two compounds are delaying gastric emptying simultaneously, against a narrow-therapeutic-index drug.
Compounded gastroparesis risk in combination
Both amylin and GLP-1 agonism slow emptying. Stacking them stacks that effect, including any associated anaesthesia aspiration risk.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Nausea disproportionate to dose when added on top of an incretin
Community reports frequently describe adding cagrilintide to an existing GLP-1 or triple agonist and getting a larger GI hit than the small dose suggests. Consistent with additive mechanism.
Marked constipation
Reported more prominently than nausea in long-run community logs, and the usual reason for adding fibre and magnesium.
Early satiety leading to under-eating protein
A recurring practical complaint: total intake falls so sharply that protein targets become difficult, which directly undercuts the lean-mass-preservation rationale for the stack.
Product identity uncertainty
Cagrilintide is chemically demanding to synthesise. Community third-party testing threads report variable content in grey-market vials more often than for simpler peptides.
03 Dosing ranges
Figures below are documented, not recommended. Study ranges come from published protocols in the stated model; grey-market ranges are what the research community reports using and carry no safety validation of any kind.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Phase 2 monotherapy dose range [1]
Once-weekly subcutaneous doses of 0.3, 0.6, 1.2, 2.4 and 4.5 mg were evaluated against placebo and liraglutide 3.0 mg over 26 weeks, with protocol-driven escalation.
Combination dosing with semaglutide [2][3]
The CagriSema programme pairs cagrilintide 2.4 mg with semaglutide 2.4 mg once weekly as a fixed-dose combination, reached by co-escalation.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Sub-milligram partner dosing
If the objective is dose-sparing an incretin rather than maximal monotherapy weight loss, a fraction of the trial dose is a defensible inference. There is no dose-response data below 0.3 mg.
Match the incretin injection day
Both compounds have half-lives of roughly a week, so same-day administration keeps exposure profiles aligned. Convenience-driven reasoning; unstudied.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
0.5 mg weekly alongside retatrutide
The dose specified in the Gold Standard protocol — roughly one-fifth of the top monotherapy trial dose, used purely as an appetite-suppression partner.
1–2 mg weekly for stronger satiety
Reported by users who escalate the cagrilintide side rather than the incretin side when weight loss stalls, on the argument that amylin-side escalation costs fewer side effects. Untested claim.
Same-syringe co-administration with retatrutide
Frequently reported for convenience. Mixing two separately reconstituted peptides in one syringe introduces compatibility, pH and stability questions nobody in that setting is testing for.
| Community use | Weekly dose | Stated intent |
|---|---|---|
| Partner dose | 0.25 – 0.5 mg | Dose-spare the incretin; minimal added GI burden |
| Standard partner | 0.5 – 1 mg | Meaningful early satiety alongside reta/sema |
| Escalated partner | 1 – 2.4 mg | Break a plateau without raising the incretin |
| Monotherapy (rare) | 2.4 – 4.5 mg | Trial-equivalent; seldom used in the community |
04 Synergy & interactions
Combination effects. Almost no peptide combination has been studied as a combination in humans; stack logic is overwhelmingly mechanistic inference and community practice. Each linked compound has its own page.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Cagrilintide + semaglutide (CagriSema) [2][3]
The only amylin + incretin combination with human trial data at scale. Phase 1b established tolerability and additive effect; phase 3 confirmed weight reduction substantially beyond semaglutide alone. This is the evidentiary anchor for every amylin-plus-incretin stack in circulation.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Cagrilintide + retatrutide
Direct extrapolation from CagriSema: separate satiety pathways, additive effect, dose-sparing on the incretin side. Never studied as this pair. The transferability assumption is that retatrutide behaves like semaglutide as a combination partner, which is not a given — retatrutide carries a glucagon arm semaglutide does not.
Cagrilintide + GH secretagogue for lean-mass retention
Same rationale as for any aggressive fat-loss agent. Unstudied in combination.
Interaction caution: insulin and sulfonylureas [6]
By class precedent (pramlintide), amylin agonism added to insulin therapy raises severe hypoglycaemia risk and requires insulin dose reduction. Nothing in the grey-market literature accounts for this.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Reta + Cagri as the standard metabolic pairing
By far the most common community use of cagrilintide. Both once-weekly, frequently co-administered on the same day.
Cagri added late to break a plateau
Reported as an alternative to escalating the incretin. Coherent with the dose-sparing argument; no data.
Cagri with tesamorelin during a cut
Reported in visceral-fat-focused stacks. Untested combination.
05 Protocols
Whole schedules — dosing, titration, cycle length, and off-time — as documented in trials, as proposed from mechanism, and as circulated in the research community. Reproduced for study and comparison only.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Phase 2 monotherapy protocol [1]
26-week randomised design with fixed escalation to target dose, against placebo and an active comparator, with defined GI-tolerability management rules.
REDEFINE phase 3 combination protocols [4]
Registered protocols for the fixed-dose combination in obesity and type 2 diabetes, including escalation schedules, monitoring and stopping rules.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Escalate the amylin side before the incretin side
If the goal is minimising total adverse-event burden, raising the better-tolerated partner first is a defensible inference. It is not how either trial programme was run.
Hold both at the lowest effective pair
Given that both components have dose-ordered GI effects, the minimum-exposure position is to stop escalating either once appetite control is adequate.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Gold Standard Protocol — 0.5 mg weekly, fixed
Cagrilintide is held at a fixed 0.5 mg weekly while retatrutide is the titrated variable. Reproduced as circulated.
15-Compound Matrix — Q1 metabolic phase
Introduced with retatrutide in the opening quarter, before regenerative and neuro compounds are layered in.
05b Condition-specific interest: type 2 diabetes, PCOS & hypothyroidism
Cagrilintide is an amylin analogue, not an incretin. The PCOS evidence people cite for this class is not evidence about this compound, and the mechanism it works by is a different one.
No approval, no trial
Cagrilintide is investigational and not approved as a single agent anywhere. It has never been studied in PCOS or hypothyroidism. The randomised PCOS evidence in this space is for GLP-1 receptor agonists — a different drug class acting on a different receptor.
Not studied as a single agent
Type 2 diabetes — only as half of CagriSema
Pathophysiology
Amylin is co-secreted with insulin and is deficient in diabetes alongside it. Replacing it slows gastric emptying, suppresses glucagon after meals and increases satiety — a genuine physiological gap, and the reason pramlintide exists at all.
Mechanistic rationale
Cagrilintide has no standalone type 2 diabetes indication and no standalone phase 3 programme. Its diabetes evidence exists only as part of CagriSema: REDEFINE-2 reported 13.7% weight loss and a 2.0 percentage point HbA1c reduction, and the REIMAGINE programme then beat semaglutide head-to-head. Those results belong to the combination, at the trialled 2.4/2.4 mg ratio, co-escalated — not to cagrilintide assembled alongside whatever incretin someone already has. An NDA for the combination was filed in December 2025 with a decision expected in late 2026, which would still leave cagrilintide unapproved as a single agent.
Community reports
Community use is almost entirely as a partner compound. The amylin-class precedent that matters here is pramlintide, which carries a boxed warning for severe insulin-induced hypoglycaemia and requires prandial insulin to be halved when it is started. Nobody adding grey-market cagrilintide to an insulin regimen is halving anything.
Components carrying the argument: Amylin / calcitonin receptors — gastric emptying, glucagon suppression, satiety
Theorized — weaker than the incretin case
PCOS — indirect at best
Pathophysiology
Insulin resistance drives hyperinsulinaemia, which stimulates ovarian androgen production and suppresses SHBG. Weight loss improves insulin sensitivity and, through it, the hormonal picture.
Mechanistic rationale
Amylin agonism produces satiety and weight loss, and weight loss improves PCOS — so the pathway to benefit runs entirely through weight rather than through a direct metabolic action on insulin signalling. That is a longer route than the incretin case, which improves insulin sensitivity directly as well as via weight. In practice cagrilintide is used as a dose-sparing partner rather than alone, so its contribution in PCOS is difficult to separate from whatever incretin it accompanies.
Community reports
No meaningful PCOS-specific reporting exists for cagrilintide alone, because it is almost never used alone.
Components carrying the argument: Amylin / calcitonin receptors — weight-mediated only
Actionable
Hypothyroidism — the levothyroxine interaction still applies
Pathophysiology
Levothyroxine is narrow-therapeutic-index, fasting-dependent and highly sensitive to gastric conditions and timing.
Mechanistic rationale
Amylin agonism slows gastric emptying independently of any incretin — it is part of how the compound produces satiety. So the levothyroxine absorption interaction is not something cagrilintide avoids by being a different class; it contributes to it. In a reta+cagri or sema+cagri stack, two compounds are slowing gastric emptying at once, which is worth knowing before attributing a thyroid drift to one of them.
Community reports
Community reports of disproportionate GI effects when adding cagrilintide to an established incretin are consistent with additive gastric-emptying delay.
Components carrying the argument: Amylin-mediated gastric emptying delay
| Question | Position |
|---|---|
| Approved for type 2 diabetes? | No — no standalone programme |
| Diabetes evidence | Only within CagriSema — REDEFINE-2 and REIMAGINE |
| Amylin + insulin | Hypoglycaemia — pramlintide carries a boxed warning |
| Approved as a single agent? | No — investigational |
| Studied in PCOS? | No |
| Does GLP-1 PCOS evidence apply? | No — different class, different receptor |
| Route to PCOS benefit | Weight loss only — indirect |
| Thyroid interaction | Yes — slows gastric emptying in its own right |
| In a stack | Two compounds delaying gastric emptying at once |
| Serious interaction | Amylin class + insulin — hypoglycaemia (pramlintide precedent) |
What actually has evidence for these conditions
PCOS has treatments that work. Metformin is first-line for the metabolic phenotype; combined hormonal contraceptives address hyperandrogenism and cycle regulation; letrozole is first-line for ovulation induction; inositol has reasonable evidence and an excellent safety profile; approved GLP-1 receptor agonists now have randomised evidence in this population. Weight loss of 5–10% alone restores ovulation in a meaningful proportion.
Levothyroxine is inexpensive, once daily, titrated against a reliable blood test, and restores euthyroid status in most people. Nothing here treats the thyroid. The unglamorous first move in someone still gaining weight is confirming replacement is adequate and correctly taken — fasting, away from calcium, iron, coffee and proton pump inhibitors.
06 Handling, reconstitution & storage
Physical-chemistry reference for laboratory handling of the lyophilised material. Reproduced so that stability and concentration mathematics can be studied — see the calculator for the arithmetic and the reconstitution guide for sterile technique.
Reconstitution
Supplied lyophilised, commonly 5 or 10 mg per vial. Reconstituted with bacteriostatic water. At a 0.5 mg weekly partner dose a 5 mg vial represents ten weeks of use, so the practical stability question is a long one.
Storage
Lyophilised: −20 °C. Reconstituted: 2–8 °C, protected from light. Amylin analogues are aggregation-prone by nature — native amylin is the archetypal amyloidogenic peptide — so agitation and temperature cycling matter more here than for most compounds.
Common vial sizes
Most commonly 5 mg and 10 mg lyophilised vials.
Stability notes
Any visible haze, fibril or particulate should be treated as aggregation. Amylin family peptides form amyloid fibrils readily; a cloudy vial is not a cosmetic issue.
07 Legal & regulatory status
Regulatory status changes and differs by country. This is a summary for orientation, not legal advice — check your own jurisdiction.
Investigational as a single agent. Cagrilintide is not approved anywhere on its own, though the CagriSema combination is under FDA review with a decision expected in the fourth quarter of 2026. The fixed-dose combination with semaglutide has progressed through phase 3 and is subject to regulatory review in various territories; that does not confer any approval on standalone grey-market cagrilintide.
Note the distinction between cagrilintide and pramlintide: pramlintide is an approved amylin analogue with a defined label, a boxed hypoglycaemia warning and decades of post-marketing data. Cagrilintide has none of that.
Regulatory and trial claims re-checked against primary sources on 16 August 2026. Checked: REDEFINE-2 and REIMAGINE figures; CagriSema NDA status. Approvals, trial readouts and compounding decisions move faster than anything else on this page — a date here means someone looked, not that nothing has changed since.
Anti-doping
Athletes subject to WADA, USADA, UKAD, NCAA or military testing should assume any peptide is prohibited unless they have verified otherwise against the current WADA Prohibited List. Several classes here (growth-hormone secretagogues, TB-4 analogues, metabolic modulators) are explicitly named. Check the current list — it is republished annually.
§ Sources & further reading
Links resolve to PubMed records, trial registries, publisher pages or primary documents. Where a body of work rather than a single paper is cited, the link opens a PubMed query so the full result set — including newer papers than this page — can be reviewed. Verify every claim against the primary source before relying on it.
- Lau DCW, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo- and active-controlled, dose-finding phase 2 trial. Lancet. 2021;398(10317):2160–2172.Registered clinical trial
- Enebo LB, et al. 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. 2021;397(10286):1736–1748.Registered clinical trial
- Efficacy and safety of cagrilintide alone and in combination with semaglutide (CagriSema): systematic review and meta-analysis.Review or meta-analysis
- ClinicalTrials.gov: registered cagrilintide and CagriSema trials (REDEFINE programme)Registered clinical trial
- PubMed: amylin analogue pharmacology, satiety signalling and leptin sensitivity (live query)Database or literature search
- FDA label: pramlintide (Symlin) — approved amylin analogue, boxed hypoglycaemia warningRegulatory / official document
Reminder
For educational and research reference only. Nothing on this site is medical advice, a recommendation, or an instruction to administer any substance to a human being. Every figure on this page is a record of what has been reported, not a recommendation. Full disclaimer.