Atlas/ Metabolic / Weight Peptides/ Amylin Analogues/ Cagrilintide
Reading depth · audience layer
Class 01 · Metabolic / weight peptides · Long-acting amylin analogue · Dual amylin + calcitonin receptor agonist · Once-weekly SC

Cagrilintidethe long-acting amylin analogue behind CagriSema

Cagrilintide is an experimental, long-acting version of the natural hormone amylin, which the pancreas releases with insulin to signal fullness after eating. It is being studied for weight management — most prominently paired with semaglutide as CagriSema — and produced strong weight loss in trials. But it is not FDA-approved, and the FDA has stated plainly that cagrilintide is not part of any approved drug, has not been found safe and effective for any condition, and cannot legally be used in compounding. It is not a legal compounded medication, despite being sold online as one.

A lipidated, long-acting amylin analogue (a dual amylin/calcitonin receptor agonist) engineered by Novo Nordisk for once-weekly subcutaneous dosing, with a human half-life of ~159–195 hours. It produces dose-dependent weight loss as monotherapy (phase 2) and larger reductions in the fixed-dose CagriSema combination with semaglutide (phase 3 REDEFINE). Per the FDA, cagrilintide is not a component of an approved drug, has not been found safe/effective for any condition, and cannot be used in compounding under federal law — strong trial data and non-approval coexist here.

Cagrilintide (AM833 / NNC0174-0833 / NN9838; CAS 1415456-99-3; C₁₉₄H₃₁₂N₅₄O₅₉S₂, MW ≈ 4409 Da; PubChem CID 167312356; DrugBank DB18887) is built on a pramlintide-like 37-residue backbone (chosen over native h-amylin to limit amyloid-fibril formation) with substitutions and an N-terminal C20 eicosanedioic fatty-diacid acylation via a γ-glutamyl spacer. This albumin-binding lipidation gives the long half-life enabling weekly dosing; it is a nonselective agonist of amylin receptors (AMY1/2/3R) and the calcitonin receptor.

~7 days Half-life (159–195 h) · once-weekly SC
~22.7% CagriSema weight loss · REDEFINE 1, 68 wk
Phase 3 REDEFINE program · investigational
Not approved FDA: not compoundable · S0 (WADA)
Status
Investigational · not FDA-approved · not compoundable
Read the FDA position & safety
Targets
Amylin receptors (AMY1/2/3R) + CTR
Combination
CagriSema (+ semaglutide 2.4 mg)
Developer
Novo Nordisk · Kruse et al. 2021
01 · At a glance

Strong trial data — and an unambiguous non-approval.

Cagrilintide is unusual in this atlas: it has genuine phase 3 evidence behind it, yet it is explicitly not approved and explicitly not legal to compound. Both facts matter. It represents a real new drug class — the first amylin-pathway agent reaching late-stage obesity development — but the gray-market "research cagrilintide" sold online is unapproved, often mislabeled as compoundable, and unverified. Below, the trial reality and the regulatory reality are kept side by side.

🍽️
Primary use case
Weight loss
Investigational anti-obesity peptide, studied as once-weekly SC monotherapy and as CagriSema with semaglutide. Grade A/B.
🔑
Mechanism headline
Amylin agonist
Mimics amylin via calcitonin-family amylin receptors to increase satiety and reduce energy intake. Grade B/P.
📊
Strongest evidence
Phase 3 (combo)
Phase 3 RCT evidence for cagrilintide + semaglutide; standalone cagrilintide has phase 2 data. Grade A/B.
⚖️
Studied doses
0.16–4.5 mg/wk
Once-weekly SC cagrilintide 0.16–4.5 mg; CagriSema uses 2.4 mg cagrilintide + 2.4 mg semaglutide. Grade B.
🤢
Key risk
GI effects
Main tolerability issue is GI adverse events — nausea, vomiting, diarrhea, constipation; dehydration and diabetes-med interactions matter. Grade B/D.
📉
Trial nuance
Below hype
CagriSema's phase 3 results, while significant, came in below the headline expectations set for the program. Grade A.
🏛️
Regulatory status
Not compoundable
FDA: not approved, not found safe/effective for any condition, and cannot be used in compounding under federal law. Grade D.
⏱️
Pharmacokinetics
~7-day t½
Half-life 159–195 h via fatty-diacid albumin binding — enabling once-weekly dosing. Grade B.
02 · Mechanism of action

How cagrilintide recreates amylin signaling.

Cagrilintide is engineered to do what the pancreatic hormone amylin does — tell the brain you're full — but for a week at a time. It engages calcitonin-family amylin receptors in the hindbrain and hypothalamus to reduce hunger and meal size, slows gastric emptying, and (in the amylin class) supports post-meal glucose control. Its design solves amylin's two problems: a tendency to clump into amyloid fibrils (fixed with a pramlintide-like backbone) and a very short half-life (fixed with fatty-acid lipidation). The receptor biology is established for the amylin class (Grade B); cagrilintide-specific human detail is partly inferred.

Grade B/P
🔑

1 · Amylin-receptor agonism & satiety

Cagrilintide copies natural amylin's appetite-regulating effect, helping the brain register fullness.
Clinical significance: Amylin analogues reduce food intake and body weight by engaging central satiety networks. Cagrilintide is a nonselective agonist of amylin receptors (AMY1/2/3R) and the calcitonin receptor — the molecular basis for its appetite suppression.
Molecular detail: Amylin receptors are calcitonin-receptor (CTR) cores complexed with RAMP proteins (RAMP1/2/3 → AMY1/2/3R). Structural and dynamic work shows cagrilintide's amylin-like binding with distinct calcitonin-family receptor conformational dynamics, distinguishing it from native amylin and pramlintide.
Grade B/P
🧠

2 · Area postrema / hindbrain control

Cagrilintide reduces hunger through brainstem regions that sense metabolic signals.
Clinical significance: Amylin biology strongly implicates the area postrema and nucleus tractus solitarius in satiety and meal-size regulation. Amylin acts on these hindbrain circuits to influence satiety and gastric emptying — the entry point for cagrilintide's central effect.
Molecular detail: The area postrema lies outside the blood-brain barrier, giving circulating amylin agonists direct access. Acylation position was tuned partly to control access to amylin receptors and the brain; hindbrain activation propagates to hypothalamic and reward feeding pathways.
Grade P/C
⚖️

3 · Hypothalamic energy-balance modulation

Cagrilintide helps shift the body toward lower energy intake.
Clinical significance: Appetite, satiety, and energy balance are regulated through hypothalamic networks, and amylin analogues reduce meal size and total intake. Amylin integrates with other appetite signals to lower energy intake.
Molecular detail: Downstream effects likely involve hypothalamic integration of amylin-receptor signaling with leptin, insulin, and GLP-1 tone. Amylin can enhance leptin sensitivity in preclinical models — a proposed basis for combination synergy. Partly inferred from amylin-class biology.
Grade B/P

4 · Gastric-emptying modulation

Amylin-type drugs slow how quickly food leaves the stomach, supporting fullness.
Clinical significance: Delayed gastric emptying can reduce post-meal glucose excursions and contribute to early satiety, though the magnitude can attenuate over time. CagriSema programs include dedicated appetite and gastric-emptying studies.
Molecular detail: Amylin-receptor signaling interacts with vagal/autonomic control of gastric motility. The gastric-slowing effect is a class feature of amylin; its durability and contribution to long-term weight loss vs the central satiety effect remain under study for cagrilintide specifically.
Grade C/P
🍬

5 · Glucagon suppression / post-prandial glucose

Amylin analogues help control post-meal glucose by reducing inappropriate glucagon.
Clinical significance: In diabetes physiology, amylin replacement (pramlintide) has been used as an insulin adjunct to improve post-prandial control. Amylin suppresses post-prandial glucagon and slows gastric emptying, smoothing glucose curves. Cagrilintide's own glycemic role is still investigational.
Molecular detail: Glucagon suppression plus delayed nutrient delivery reduces post-meal hyperglycemia. REDEFINE 2 evaluated glycemic outcomes in type 2 diabetes; the effect in cagrilintide arms is intertwined with weight loss and semaglutide co-therapy.
Grade A/B
🤝

6 · GLP-1 synergy (with semaglutide)

Cagrilintide pairs with GLP-1 drugs because they curb appetite through overlapping but distinct pathways.
Clinical significance: CagriSema combines amylin-analogue signaling with GLP-1 receptor agonism, producing greater weight loss than placebo in phase 3. In REDEFINE 1, CagriSema outperformed placebo and each component alone.
Molecular detail: GLP-1 and amylin receptor signaling converge on appetite, gastric, and metabolic circuits with additive/synergistic satiety effects. REDEFINE 1 reported CagriSema ≈ −22.7% vs cagrilintide alone ≈ −11.8% and semaglutide alone ≈ −16.1% — evidence the combination adds beyond either alone.
L3 · Cascade
From weekly injection to weight loss
💉 SC cagrilintide
weekly · long t½
🔑 Amylin / CTR
receptor complex
🧠 Satiety circuits
hindbrain + hypothalamus
🍽️ ↓ Intake
+ slowed emptying
⚖️ Weight loss
↑ with semaglutide
L3 · Molecular design
How cagrilintide fixes amylin's two problems
Amylin problemCagrilintide solutionResult
Forms amyloid fibrilsPramlintide-like backbone (not h-amylin)Reduced fibrillation
Very short half-lifeC20 eicosanedioic diacid via γ-glutamyl spacerAlbumin binding → ~7-day t½
Receptor potencyAmino-acid substitutionsEnhanced amylin/CTR activity
Dosing burden (pramlintide = 3×/day)Long-acting designOnce-weekly SC
L3 · Receptor family
The amylin / calcitonin receptor system
ReceptorCompositionRole
CTR (calcitonin receptor)Core GPCRCalcitonin signaling; amylin-receptor core
AMY1RCTR + RAMP1Amylin satiety signaling
AMY2RCTR + RAMP2Amylin signaling
AMY3RCTR + RAMP3Amylin signaling
CagrilintideNonselective agonistEngages all of the above
03 · Dosing models (trial-anchored, research-only)

Real trial doses — but no approved, no compoundable protocol.

Cagrilintide has well-defined doses from human trials (phase 2 dose-finding and the CagriSema phase 3 program), so the numbers below are real exposure data rather than guesses. But they are not a prescribing protocol: cagrilintide has no approved label, and the FDA states it cannot be used in compounding under federal law. Protocol cards display the trial-reported mg/week amounts; the calculator handles µg reconstitution arithmetic only. None of this is medical guidance.

FDA: not approved and not compoundable Per the FDA (content current February 4, 2026), cagrilintide cannot be used in compounding under federal law; it is not a component of an FDA-approved drug and has not been found safe and effective for any condition. Online "research" or "compounded" cagrilintide is unapproved, frequently mislabeled, and of unverified quality. Weight management should be pursued with a qualified clinician and FDA-approved options.
Pharmacokinetics Phase 1b reported a half-life of 159–195 h after once-weekly SC dosing (0.16–4.5 mg), with median Tmax 24–72 h; Cmax ranged ~6.1–170 nmol/L and AUC₀–₁₆₈h ~926–24,271 nmol·h/L across the dose range. The ~7-day half-life is why cagrilintide is dosed weekly and why washout takes weeks, not days.
Subcutaneous weekly — standalone (trial model)
Phase 2 dose-finding exposure · not a prescription
Grade B/D
Trial doses
Phase 2 used 0.3, 0.6, 1.2, 2.4, and 4.5 mg once weekly; 4.5 mg produced ~10.8% weight loss over 26 weeks.
Escalation
Trials escalated no faster than ~every 4 weeks, gated on GI tolerability and hydration.
Dose ladder
0.3 → 0.6 → 1.2 → 2.4 mg/wk; 4.5 mg/wk is a high trial-exposure reference, not a default.
Window / washout
Trial treatment windows ~16–68 weeks; ~7-day half-life means multi-week washout.
Monitoring
GI symptoms, hydration, weight, appetite, BP, glucose/HbA1c if diabetic, drug interactions.
Not approved; not compoundable. Avoid in pregnancy, severe GI-motility disease, active eating disorder, or unexplained weight loss; not for self-administration. Grade B/D.
Dose bands · trial-derived
Global dose-band table (trial exposure, not prescribing)
BandWeekly dose≈ µg/weekBasis
Low0.3–0.6 mg300–600 µgPhase 2 lower arms
Standard1.2–2.4 mg1200–2400 µgPhase 2/3 target exposure
High4.5 mg4500 µgPhase 1b/2 high exposure
Weight-band · conversion only
Weekly dose → approximate µg/kg/week (not a prescribing table)
Body weight0.3 mg0.6 mg1.2 mg2.4 mg4.5 mg
55 kg5.510.921.843.681.8
65 kg4.69.218.536.969.2
75 kg4.08.016.032.060.0
85 kg3.57.114.128.252.9
95 kg3.26.312.625.347.4
105 kg2.95.711.422.942.9

Units = µg/kg/week. Conversion for trial literacy only — cagrilintide is dosed as a fixed weekly amount, not by body weight.

Titration logic
Titration / safety decision logic
TriggerActionRationale
Mild nausea, stable intake/hydrationHold dose longer; don't escalateGI AEs are common with amylin/GLP-1 agents
Persistent vomiting, dehydration, orthostasisHold; clinical evaluationDehydration worsens renal risk
Rapid unintended / excessive weight lossDe-escalate or holdPrevent undernutrition / lean-mass loss
Severe abdominal pain radiating to backHard stop; urgent evaluationPancreatitis / gallbladder differential
Hypoglycemia (on insulin/sulfonylurea)Hold escalation; med reviewFalling intake + unchanged hypoglycemics
Pregnancy or planned pregnancyHard stopNo established pregnancy safety
Biomarker scaffold
Monitoring scaffold
MetricPurposeCadence
Body weightEfficacy (trial endpoint)Weekly–monthly
Waist circumferenceCardiometabolic trendMonthly
Blood pressureSafety / effectBaseline + monthly
HbA1c / fasting glucoseGlycemia (if diabetic)Baseline + 3 mo
CMP / creatinineDehydration / renalIf vomiting/dehydration
Body composition / lean massMuscle preservationEvery 8–12 wk
CagriSema combination (trial model)
Cagrilintide + semaglutide · phase 3 REDEFINE
Grade A/B
Trial composition
Phase 3 CagriSema used 2.4 mg cagrilintide + 2.4 mg semaglutide once weekly; phase 1b paired cagrilintide 0.16–4.5 mg with semaglutide 2.4 mg.
Titration
Both components titrated slowly to target, since GI AEs are dose/titration-sensitive; do not start at full target.
Trial window
REDEFINE phase 3 trials ran 68 weeks.
Efficacy
REDEFINE 1: ~22.7% weight loss at 68 weeks vs ~2.3% placebo; REDEFINE 2 (T2D): ~13.7%.
Monitoring
GI AEs, dehydration, gallbladder/pancreatitis symptoms, glycemia if diabetic, body composition, renal function.
Additive GI intolerance; diabetes meds may need adjustment. Investigational fixed-dose combination — not an approved product to assemble independently. Grade A/B (trial) · D (extrapolated use).
REDEFINE results
CagriSema vs components (REDEFINE 1, 68 wk)
ArmWeight changevs placebo
Placebo≈ −2.3%
Cagrilintide 2.4 mg alone≈ −11.8%−9.5 pp
Semaglutide 2.4 mg alone≈ −16.1%−13.8 pp
CagriSema 2.4/2.4 mg≈ −22.7%−20.4 pp
Daily / frequent microdosing
Not the trial basis
Grade D/P
Rationale
Cagrilintide was engineered for once-weekly dosing via its long half-life — splitting into daily doses contradicts the design.
Evidence
No validated escalation, ladder, or maintenance for microdosing.
Higher dosing-error and exposure-variability risk; should not be presented as a validated protocol. Grade D/P.
Why weekly
The long half-life is the point
FeatureImplication
~159–195 h half-lifeSteady exposure across a week
Albumin-binding depotSmooth absorption from SC site
Daily splittingNo benefit; adds error
Oral route
Not established
Grade P/D
Evidence
No established oral cagrilintide protocol in human clinical evidence.
Note
Oral peptide delivery needs specialized formulation; do not convert injectable mg doses to oral use.
Not modeled. Grade P/D.
Oral barrier
Why oral isn't a route here
BarrierDetail
ProteolysisGI degradation of the peptide
AbsorptionLow oral bioavailability
DesignBuilt for SC depot delivery
Intranasal / IV / IM
Not established
Grade D/P
Evidence
Human obesity development is subcutaneous weekly; no reliable intranasal, IV, or IM cagrilintide protocol exists.
Note
Do not infer from unrelated peptides or unregulated marketplace patterns.
Avoid — no trial basis, unknown exposure, sterility/safety risk. Grade D/P.
Route reality
SC is the only studied therapeutic route
RouteStatus
Subcutaneous weeklyTrial-studied
Intranasal / IV / IMNot established
OralNot established
L2 · Reconstitution math (research only)

Reconstitution & Dose Calculator

This calculator validates concentration and draw-volume arithmetic only — the same mg→mL math used throughout the atlas. It is not a prescribing tool. Cagrilintide is not FDA-approved and, per the FDA, cannot be used in compounding under federal law; there is no approved commercial vial, so the sizes below are configuration examples only. Weight management belongs with a clinician and approved options, not self-administered unapproved peptide.

Concentration
Draw volume
Units (U-100)
Doses/vial
Basis
04 · Combinations

Combinations — one defines the molecule.

Cagrilintide's most important combination isn't a "stack" — it's the entire reason much of the development happened: pairing it with semaglutide as the fixed-dose investigational product CagriSema. That combination has phase 3 evidence. The others below are context (lifestyle, background diabetes therapy) or cautionary (other incretins). Because both cagrilintide and semaglutide are long-acting and GI-active, the dominant theme is additive gastrointestinal intolerance and the need for slow, supervised titration.

Cagrilintide + Semaglutide (CagriSema)
Phase 3 evidence
Cagrilintide 2.4 mg Semaglutide 2.4 mg Weekly SC
The defining combination: amylin-analogue satiety plus GLP-1 receptor agonism. CagriSema 2.4/2.4 mg weekly produced ~22.7% weight loss at 68 weeks in REDEFINE 1 — beyond either component alone. This is an investigational fixed-dose product, not a DIY stack, and still not FDA-approved. Grade A.
ComponentMechanismGrade
CagrilintideAmylin/CTR agonistA
SemaglutideGLP-1 receptor agonistA
Cagrilintide + Lifestyle Intervention
Trial foundation
Cagrilintide Diet Physical activity
Every major trial layered the drug on top of reduced-calorie diet and increased activity. All cagrilintide obesity trials included lifestyle support. The drug effect should not be interpreted outside that context — lifestyle is the foundation, not an optional add-on. Grade A/B.
ElementRole
Diet + activityTrial backbone
CagrilintideAdd-on in that context
Cagrilintide + Diabetes Background Therapy
Trial context (T2D)
Cagrilintide Metformin ± SGLT2i
In the type 2 diabetes program, cagrilintide/CagriSema was studied alongside background glucose-lowering therapy. REDEFINE 2 studied adults with T2D on standard background regimens. Hypoglycemia risk rises if appetite/intake falls while insulin or sulfonylurea doses stay fixed — medication review is essential. Grade A/B.
Co-therapyConcern
Insulin / sulfonylureaHypoglycemia as intake falls
Metformin / SGLT2iGenerally lower hypo risk
Cagrilintide + Tirzepatide / other incretins
Caution · not established
Cagrilintide Tirzepatide / GLP-1 / GIP
A competitive/comparison landscape exists, but routine stacking of cagrilintide with other potent incretins is not established. Comparative development context exists, but co-use is not validated. Overlapping GI and metabolic effects raise intolerance and safety risk — avoid casual stacking. Grade D.
ComboStatus
+ TirzepatideNot established · caution
+ other amylin/GLP-1Additive GI risk
Hard-constraint clinical note — Do not stack cagrilintide with other potent appetite/incretin/amylin agents in anyone with severe gastroparesis, active eating disorder, pregnancy, uncontrolled vomiting/dehydration, or unexplained abdominal pain. The only evidence-backed combination is the investigational CagriSema fixed-dose product studied under trial supervision — and even that is not FDA-approved. Obesity and diabetes are managed conditions; an unapproved, non-compoundable peptide is not a substitute for supervised, approved care.
05 · Safety & contraindications

Predictable GI tolerability — plus a hard regulatory line.

In trials, cagrilintide's safety profile is dominated by gastrointestinal effects — nausea, vomiting, diarrhea, constipation — the same class signature seen with amylin and GLP-1 agents, and the main reason for slow titration. Beyond the molecule, the larger real-world risks are regulatory and practical: cagrilintide is not approved and not legally compoundable, so gray-market product carries quality, sterility, and dosing-error hazards on top of the pharmacology.

Safety signals & risks
NauseaThe most common GI tolerability signal in cagrilintide/CagriSema studies. Grade B.
VomitingClinically relevant for dehydration risk; reported in incretin/amylin contexts. Grade B.
Diarrhea / constipationGI AEs reported across obesity trials. Grade B.
Excessive appetite suppressionThe intended effect can become undernutrition/lean-mass loss if unchecked. Grade B/D.
Pancreatitis / gallbladder differentialSevere abdominal pain needs urgent evaluation, especially with incretin co-therapy and rapid weight loss. Grade D.
Hypoglycemia (in T2D)Mainly with insulin/sulfonylureas or falling intake. Grade D.
Unverified gray-market productNot approved or compoundable — quality, sterility, and dosing-error risk. Grade D.
Pregnancy / fetal riskNo established pregnancy safety — avoid. Grade D.

Practical safety framework

GI tolerability drives titration

Most adverse effects are dose- and titration-dependent GI symptoms. Slow escalation, adequate hydration, and holding (not pushing) the dose when nausea appears are the core tolerability levers — exactly as in the trials.

Watch the high-acuity differentials

Severe abdominal pain (pancreatitis/gallbladder), persistent vomiting with dehydration, and hypoglycemia in insulin/sulfonylurea users are the events that warrant stopping and urgent evaluation rather than dose adjustment.

The regulatory line is a safety line

Because cagrilintide is not approved and not compoundable, gray-market product is unverified. The safest path for weight management is a clinician and FDA-approved options — not self-sourced unapproved peptide.

Contraindications & cautions

Condition / scenarioConcernSeverity
Pregnancy / breastfeedingNo established safetyHigh
Active eating disorderAppetite suppression may worsen harmHigh
Severe gastroparesisMechanistic worsening of motilityHigh
Recurrent vomiting / dehydrationRenal / electrolyte riskHigh
Unexplained severe abdominal painPancreatitis / gallbladder differentialHigh
Hypersensitivity to componentAllergy riskHigh
Unverified "research" productQuality / sterility / dosing uncertainty; not compoundableHigh
Diabetes on insulin/sulfonylurea (unmonitored)Hypoglycemia riskModerate–High
Advanced renal disease + poor intakeDehydration sensitivityModerate–High
Competitive athlete (WADA)S0 non-approved substanceHigh
Rapid / excessive weight lossLean-mass loss, malnutritionMonitor
Casual stacking with other incretinsAdditive GI / metabolic effectsAvoid
06 · Evidence base

Phase 3 evidence — with an honest asterisk.

Cagrilintide has the strongest clinical evidence of any unapproved peptide in this atlas: a published phase 1b PK study, a phase 2 dose-finding trial, and the phase 3 REDEFINE program for CagriSema. The asterisk matters too — CagriSema's headline weight-loss numbers, while significant and clinically meaningful, came in below the expectations the program had set, which moved markets and tempered the "next big thing" narrative. The honest read: real, high-quality evidence for a real effect, on a drug that is still investigational and not approved.

Phase 1b · 2021
t½ 159–195 h
Enebo et al.: cagrilintide + semaglutide PK/safety supported once-weekly dosing. Lancet.
Phase 2 · 2021
~10.8% (4.5 mg)
Lau et al.: dose-dependent weight loss; 4.5 mg over 26 wk beat liraglutide 3.0 mg. Lancet.
Phase 3 · REDEFINE 1
~22.7%
CagriSema in obesity without diabetes, 68 wk vs placebo/components. NEJM 2025.
Phase 3 · REDEFINE 2
~13.7%
CagriSema in obesity + type 2 diabetes; weight + glycemic outcomes. NEJM 2025.
APhase 3 · obesity without diabetes

REDEFINE 1 (Garvey et al. 2025) — coadministered cagrilintide + semaglutide

The pivotal obesity trial: CagriSema 2.4/2.4 mg weekly over 68 weeks produced ~22.7% mean weight loss vs ~2.3% placebo, exceeding cagrilintide alone (~11.8%) and semaglutide alone (~16.1%) — clear evidence of additive benefit, though below the program's most optimistic projections.

APhase 3 · obesity + type 2 diabetes

REDEFINE 2 (Davies et al. 2025) — CagriSema in T2D

The diabetes companion trial: CagriSema produced significant weight reduction (~13.7%) and improved glycemic outcomes vs placebo in adults with overweight/obesity and type 2 diabetes — extending the evidence into the harder-to-treat diabetic population, with the characteristic lower weight-loss magnitude seen in T2D.

BPhase 2 · dose finding

Lau et al. 2021 — once-weekly cagrilintide dose-finding

The standalone dose-finding trial across 0.3–4.5 mg weekly showed dose-dependent body-weight reduction vs placebo, with 4.5 mg producing ~10.8% loss over 26 weeks and outperforming liraglutide 3.0 mg — the basis for selecting cagrilintide doses and the strongest standalone evidence.

BPhase 1b · PK / safety

Enebo et al. 2021 — cagrilintide + semaglutide phase 1b

Established cagrilintide's human PK: half-life 159–195 h and Tmax 24–72 h after weekly SC dosing (0.16–4.5 mg with semaglutide 2.4 mg), generally tolerated — the data that confirmed once-weekly dosing was feasible and seeded the CagriSema program.

PMedicinal chemistry · development

Kruse et al. 2021 — development of cagrilintide

The design paper: selection of a stable, lipidated long-acting amylin analogue built on a pramlintide-like backbone (to limit amyloid-fibril formation) with C20 fatty-diacid acylation for albumin binding and weekly dosing — the molecular story behind the molecule.

PReceptor pharmacology · DACRA

Fletcher et al. 2021 — AM833 at calcitonin-family GPCRs

Pharmacologically characterized AM833 (cagrilintide) as a novel agonist across calcitonin-family G-protein-coupled receptors, comparing it with selective and nonselective agonists — establishing its nonselective amylin/calcitonin receptor profile. DACRA characterization.

PStructural biology · receptor dynamics

Cagrilintide binding to calcitonin-family receptors (2025)

Structural and dynamic work characterizing how cagrilintide engages calcitonin-family receptors with amylin-like binding but distinct conformational dynamics — refining the molecular basis of its receptor activity beyond native amylin and pramlintide.

C/PReview · amylin biology

Amylin: from mode of action to clinical potential (2025 review)

Reviews amylin physiology — satiety, gastric emptying, glucagon suppression, and metabolic control — providing the class context for cagrilintide's mechanism and the rationale for amylin-pathway obesity drugs. amylin biology review.

ASecondary analysis · cardiometabolic

REDEFINE cardiometabolic markers — blood pressure & hs-CRP

Secondary analyses reported CagriSema lowered systolic blood pressure and hs-CRP alongside weight loss — supportive cardiometabolic signals, though these are exploratory and not dosing-decision biomarkers. cardiometabolic analysis.

DRegulatory · FDA position

FDA — cagrilintide not approved, not compoundable

FDA's statement on unapproved GLP-1 drugs (content current Feb 4, 2026): retatrutide and cagrilintide cannot be used in compounding under federal law, are not components of FDA-approved drugs, and have not been found safe and effective for any condition — the central compliance fact for this entry.

DSponsor / regulatory status

Novo Nordisk CagriSema filing & status

Novo Nordisk filed for FDA approval of CagriSema as a once-weekly GLP-1 + amylin combination for weight management; as of the cited sources it remains in the approval process, not yet approved — an important distinction from "available." filing status.

GRADE summary — Evidence strength is high (Grade A) for the CagriSema combination via the phase 3 REDEFINE program and solid (Grade B) for standalone cagrilintide via phase 2 dose-finding and phase 1b PK; mechanism is biologically coherent but partly extrapolated from amylin-class biology (Grade P/C). The honest caveats: CagriSema's efficacy, while significant, landed below headline expectations; long-term real-world outcomes and independent post-marketing safety data don't yet exist; and the drug is not FDA-approved and not legally compoundable. Positioning: "a genuinely promising, well-studied investigational amylin analogue — not an approved or compoundable medicine, and not a self-administration peptide."
07 · Compare & contrast

Cagrilintide among the metabolic peptides.

Cagrilintide opens a distinct lane in the obesity-drug landscape: the amylin pathway, complementary to the GLP-1 (semaglutide) and GIP/GLP-1 (tirzepatide) agents that dominate today. Its closest relative is pramlintide — the only approved amylin analogue — but pramlintide is short-acting and used as a diabetes adjunct, whereas cagrilintide is long-acting and built for obesity. The table separates approved agents from cagrilintide's investigational status.

AgentMechanism classPrimary useEvidence tierRouteRegulatory status
CagrilintideLong-acting amylin/calcitonin agonistObesity (investigational)Phase 2 (solo); phase 3 (CagriSema)SC weeklyNot approved; not compoundable
PramlintideAmylin analogue (short-acting)Diabetes insulin adjunctApproved RCT evidenceSC at meals (3×/day)FDA-approved
SemaglutideGLP-1 receptor agonistT2D / obesity / CV riskLarge approved RCTsSC weekly / oralFDA-approved
TirzepatideGIP/GLP-1 receptor agonistT2D / obesityLarge approved RCTsSC weeklyFDA-approved
CagriSemaAmylin + GLP-1 (fixed-dose)Obesity / T2D (investigational)Phase 3 RCTsSC weeklyFiled; not approved

Related peptides.

09 · Reading-layer ledes

The same molecule, three depths.

L1 · Consumer — Cagrilintide is an experimental long-acting version of amylin, a natural hormone that helps you feel full after eating. It's studied for weight management, especially combined with semaglutide as CagriSema, and produced strong weight loss in trials. But it is not FDA-approved, and the FDA says it cannot legally be used in compounding — so the "research" or "compounded" cagrilintide sold online is unapproved and unverified. Weight management should go through a doctor and approved options.
L2 · Clinical — Cagrilintide is a lipidated, long-acting amylin analogue (dual amylin/calcitonin receptor agonist) for once-weekly SC dosing, with phase 2 monotherapy evidence and phase 3 REDEFINE evidence for the cagrilintide–semaglutide combination (CagriSema). It reduces appetite, energy intake, and possibly gastric emptying. It is not FDA-approved, not legally compoundable, and its phase 3 efficacy — while significant — came in below the program's headline expectations.
L3 · Research — Cagrilintide (AM833) engages calcitonin-family amylin receptors (AMY1/2/3R + CTR), built on a pramlintide-like backbone with C20 fatty-diacid acylation giving a ~159–195 h half-life. Open research questions: receptor-subtype pharmacology, the additive map of amylin + GLP-1 signaling, long-term safety and lean-mass effects, cardiometabolic outcomes, and how much of CagriSema's benefit derives from cagrilintide itself versus semaglutide — a question sharpened by the REDEFINE component-arm data.
08 · References & evidence

Source register.

Evidence grades reflect the strength of support for the specific claim cited, not the prestige of the journal. For cagrilintide, the firmest sources are the phase 3 REDEFINE NEJM papers (Grade A), the phase 2 and phase 1b Lancet trials (Grade B), the medicinal-chemistry and receptor-pharmacology work (Grade P), and the FDA regulatory statement (Grade D). This is the highest-evidence unapproved peptide in the atlas — which is exactly why the not-approved, not-compoundable status deserves equal prominence.

A · Phase 3 RCT / approval
B · Phase 1b/2 clinical
C · Review / observational
D · Regulatory / database
P · Preclinical / mechanistic
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