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Protocol · Research Dosing Guide

Cagrilintide Dosing Protocol: Weekly Titration, Reconstitution Math & Research (2026)

A research reference for cagrilintide (AM833), a long-acting acylated amylin analog dosed once weekly, covering the escalation ladder used in its clinical program, the reconstitution math for the 10 mg vial, its dual amylin/calcitonin receptor mechanism, and the monitoring the literature attaches to it.

Cagrilintide Quick Start

Cagrilintide (AM833) is a 37-amino-acid analog of amylin, the pancreatic hormone co-secreted with insulin that signals satiety and slows gastric emptying. A C20 fatty-diacid side chain binds albumin and stretches its half-life to roughly a week, so it is dosed once weekly by subcutaneous injection. It is investigational: studied alone in a 26-week Phase 2 trial and, combined with semaglutide as CagriSema, through the Phase 3 REDEFINE program. It is the first long-acting amylin analog to reach late-stage development.

Quick reference Investigational · Phase 3 (CagriSema)
Class
Long-acting amylin analog
Formats
Vial (SubQ)
Research focus
Appetite, weight, metabolic
Schedule shape
Weekly, titrated
Vial size
10 mg

This guide is an educational research reference. It does not diagnose, treat, or prescribe, and is not medical advice. Consult a licensed clinician before considering any compound.

Cagrilintide Dosing Protocol

Every cagrilintide trial dosed it once weekly, subcutaneously, with stepwise escalation to manage gastrointestinal effects. The Phase 2 monotherapy study escalated to maintenance doses of 0.3 to 4.5 mg; the Phase 3 CagriSema program escalates cagrilintide over 16 weeks to a 2.4 mg maintenance dose (0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg, roughly four weeks per step). The ladder below follows that 2.4 mg pathway. The units column assumes the 2 mL reconstitution worked out in the next section (5 mg/mL, 1 mg = 20 units). These are research-planning references, not personal dosing recommendations.

Injection — Subcutaneous (U-100 units)

10 mg + 2 mL BAC → 5 mg/mL. One dose per week; ~4 weeks per step before escalating.
PhaseWeekly doseUnits (U-100)Duration
10.25 mg5 uWeeks 1–4
20.5 mg10 uWeeks 5–8
31.0 mg20 uWeeks 9–12
41.7 mg34 uWeeks 13–16
5 (maintenance)2.4 mg48 uWeek 17 onward
5 mg/mL · 1 mg = 20 units · 2.4 mg = 0.48 mL = 48 units · ~4 maintenance doses per 10 mg vial
The Phase 2 monotherapy trial also studied a 4.5 mg weekly arm (96 units at 5 mg/mL), which produced the largest weight reduction but the most gastrointestinal events. The 2.4 mg maintenance dose is the one carried into Phase 3, so it is the better-characterised reference point.

Cycle guidelines

ApproachDurationReview pointBest for
Escalation16 weeksEach step (~4 wks)Reaching the 2.4 mg maintenance dose with tolerable GI effects
Maintenance26–68 weeks (trial durations)MonthlyMirrors the Phase 2 (26 wk) and Phase 3 (68 wk) study lengths
Hold1–2 weeks at current stepNext scheduled doseNausea or vomiting at a new step; resume escalation once tolerated

Escalation, not the final dose, is where most GI events occur. The clinical program held a step rather than reduced the dose when tolerability was the issue.

Cagrilintide Reconstitution Guide

Cagrilintide ships as a lyophilized powder in a 10 mg vial. Because the early steps are small (0.25–0.5 mg), a 2 mL reconstitution gives a readable 5-to-10-unit draw and a round 5 mg/mL concentration. A 1 mL fill doubles the concentration for smaller draws at the maintenance dose; 3 mL fits the vial but gives non-round unit figures.

Injection

BACConc.2.4 mg
2 mL5 mg/mL0.48 mL · 48 u
1 mL10 mg/mL0.24 mL · 24 u
3 mL3.33 mg/mL0.72 mL · 72 u

Units are U-100 insulin-syringe units (100 u = 1.0 mL). At 1 mL the 0.25 mg starting step is a 2.5-unit draw — hard to read accurately; 2 mL is the practical fill for the escalation phase.

Milligrams, not IU

Cagrilintide is labeled by mass. Per-unit dose = vial mg ÷ (fill mL × 100). At 2 mL that is 0.05 mg (50 mcg) per unit. The reconstitution calculator works any other volume.

Reconstitution steps

  1. Inspect the vial. Confirm the label, the 10 mg strength, and that the powder looks dry and intact.
  2. Wipe the stoppers. Use an alcohol swab on both the bacteriostatic water and peptide vial stoppers.
  3. Draw the chosen volume. 2 mL (or 1 mL for a more concentrated solution) into the vial — this is the number that sets every concentration figure above.
  4. Inject down the wall. Release the water slowly down the inside wall, not directly onto the powder.
  5. Swirl, do not shake. Roll gently until dissolved. Shaking foams and can damage the peptide.
  6. Verify clarity. Solution should be clear and colorless. Discard if cloudy or particulate.
  7. Label and refrigerate. Note the date and volume added on the vial, then store at 2–8 °C. Do not freeze the reconstituted solution.

See the bacteriostatic water guide for diluent handling, or the reconstitution calculator to work any other volume.

How Cagrilintide Works

Amylin is co-released with insulin from pancreatic beta cells after a meal and acts on the area postrema and hypothalamus to signal fullness, slow gastric emptying, and suppress post-meal glucagon. Native amylin has a half-life of minutes and aggregates readily, which is why the first amylin analog, pramlintide, has to be injected before each meal. Cagrilintide solves both problems: sequence substitutions prevent aggregation, and a C20 diacid lipid side chain binds albumin so the peptide circulates for about a week. Pharmacologically it activates both the amylin receptors (calcitonin receptor + RAMP complexes) and the calcitonin receptor itself, which is why it is sometimes described as a dual amylin and calcitonin receptor agonist.

Amylin receptor agonism

Central satiety signalling via the area postrema; reduced food intake is the primary driver of weight reduction.

Calcitonin receptor activity

Additional receptor engagement thought to contribute to the sustained effect on appetite.

Slowed gastric emptying

Delays nutrient delivery and blunts post-meal glucose and glucagon rises.

Complementary to GLP-1

Works through a separate pathway, which is the rationale for the CagriSema combination and its additive weight effect.

Who Should Avoid Cagrilintide

Cagrilintide is investigational and has no approved labeling; the cautions below transfer from the amylin-analog class (pramlintide labeling) and from its trial exclusion criteria.

Insulin or sulfonylurea co-use

Pramlintide carries a boxed warning for severe hypoglycemia when combined with insulin; the same interaction concern applies to any amylin analog.

Gastroparesis

Amylin analogs slow gastric emptying; pre-existing gastroparesis or significant GI motility disease is a class contraindication.

Pregnancy & lactation

Not appropriate; no safety data in this context and trials excluded pregnancy.

Pancreatitis history

Excluded from the clinical program; a standing caution for incretin-adjacent metabolic agents.

Cagrilintide Side Effects & Safety

Gastrointestinal

Nausea, vomiting, constipation and decreased appetite are the most common events, mostly mild to moderate, concentrated during escalation.

Injection-site reactions

Redness, itching or bruising at the site; rotate sites. Reported more often than with semaglutide alone.

Hypoglycemia

No meaningful signal as monotherapy in non-diabetic participants; the risk rises with insulin or sulfonylureas.

Titration matters

Escalating faster than the ~4-week steps used in the trials increases nausea and discontinuation; hold a step rather than push through.

Long-term data

Exposure beyond 68 weeks and outcomes data are still being generated; approval status is pending.

Timeline & What to Monitor

TimeframeCommonly trackedNotes
Weeks 1–4GI tolerability at the starting stepHold or slow escalation if nausea or vomiting is strong.
Each step (~4 wks)Tolerability before escalatingOnly advance the ladder when the current step is tolerated.
Weeks 16–26Weight, waist, fasting glucoseMaintenance dose reached; the Phase 2 primary endpoint was read at week 26.
OngoingWeight, glucose, lipids, blood pressureTrack the metabolic endpoints reported in the trials.

Cagrilintide Evidence Context

Phase 2 monotherapy

26-week, 706-participant trial: dose-dependent weight reduction up to 10.8% at 4.5 mg weekly versus 3.0% with placebo and 9.0% with liraglutide 3.0 mg daily (Lau et al., Lancet 2021).

CagriSema Phase 1b / 2

Combined with semaglutide 2.4 mg, 20-week weight loss of 17.1% (Phase 1b); 15.6% at 32 weeks in type 2 diabetes versus 5.1% with semaglutide alone (Frias et al., Lancet 2023).

Phase 3 REDEFINE program

REDEFINE 1 reported 22.7% mean weight reduction at 68 weeks for CagriSema in obesity; REDEFINE 2 reported 13.7% in type 2 diabetes. Regulatory submissions followed in 2025–2026.

Boundary

Not approved as of this review; all data are from Novo Nordisk-sponsored trials. Monotherapy Phase 3 data are not yet published.

Storage & Handling

StateStorageNotes
Lyophilized (powder)−20 °C long-term; fridge short-termProtect from light. More stable than reconstituted solution.
Reconstituted (liquid)2–8 °CUse within ~3–4 weeks; do not freeze. Avoid repeated freeze–thaw.
AppearanceClear, colorlessDiscard cloudy or particulate solutions.

Cagrilintide vs Other Appetite-Pathway Compounds

FeatureCagrilintidePramlintideSemaglutide / Retatrutide
ReceptorAmylin + calcitoninAmylinGLP-1 (± GIP, glucagon)
CadenceWeekly, titratedBefore each meal (2–3×/day)Weekly, titrated
Half-life~7 days~48 minutes~7 days
StatusInvestigational (Phase 3 as CagriSema)Approved (adjunct to insulin)Approved / Phase 3

Frequently Asked Questions

What is cagrilintide?

An investigational long-acting analog of the hormone amylin (also coded AM833), developed by Novo Nordisk. It is dosed once weekly, studied alone and in combination with semaglutide as CagriSema, and is in Phase 3.

How is it dosed?

Once weekly by subcutaneous injection, escalated in ~4-week steps. The Phase 3 pathway is 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg; the Phase 2 monotherapy trial studied up to 4.5 mg.

How is a 10 mg vial reconstituted?

Add 2 mL of bacteriostatic water for 5 mg/mL. On a U-100 syringe 1 mg is 20 units, so 0.25 mg is 5 units and the 2.4 mg maintenance dose is 48 units. A 1 mL fill halves every unit figure.

How many doses are in a vial?

About four at the 2.4 mg maintenance dose. The full 16-week escalation ladder (0.25 + 0.5 + 1.0 + 1.7 mg, each for four weeks) uses 13.8 mg, so a single vial covers most but not all of it.

How does it differ from a GLP-1 agonist?

It works through amylin and calcitonin receptors rather than GLP-1 receptors, which is why the two classes are combined in CagriSema for an additive effect on weight.

Is this page medical advice?

No. It is an educational research reference and does not diagnose, treat, or prescribe. Consult a licensed clinician before considering any compound.

Cagrilintide Formats & Sourcing

Cagrilintide is supplied as a lyophilized powder in a single 10 mg vial. There is no pre-reconstituted pen or spray format. Batch-specific Certificates of Analysis are issued per lot; always verify the strength on the label against the figures used here before calculating anything.

FormatSupplied as
Vial10 mg lyophilized powder

Strengths are listed as sold; confirm against the product page and the batch COA before calculating anything.

Reference material for this protocol, with batch COA:

View Cagrilintide on Spyro Peptides →
Purity 99+% HPLC Batch COA available Research use only

References

  1. Lau DCW, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet (2021).
  2. 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).
  3. Frias JP, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet (2023).
  4. Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). N Engl J Med (2025).
  5. Kruse T, et al. Development of cagrilintide, a long-acting amylin analogue. J Med Chem (2021).
  6. Boyle CN, et al. Amylin — its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity. Mol Metab (2018).