PEPTOPIAHEALTH & WELLNESS

Cagrilintide Guide

The long-acting amylin analogue behind CagriSema. A complete guide to mechanism, clinical evidence, reconstitution, and standard research titration protocols.

What is Cagrilintide?

Cagrilintide is Novo Nordisk's long-acting analogue of amylin — the hormone your pancreas releases alongside insulin every time you eat. It is known in the research literature as AM833 and is classified as a DACRA: a dual amylin and calcitonin receptor agonist. Where semaglutide and tirzepatide work through the incretin (GLP-1) system, cagrilintide works through an entirely separate satiety pathway — which is exactly why the two combine so well.

Satiety Signaling

🛑 Activates amylin receptors in the brainstem
🍽️ Sends the "meal is over" signal
🔇 Quiets hunger between meals

Slows Gastric Emptying

⏳ Food leaves the stomach more slowly
😌 Fullness lasts longer after eating
📉 Blunts post-meal glucose spikes

Glucagon Control

🧪 Suppresses post-meal glucagon
🩸 Smooths blood-sugar swings
🤝 Complements insulin's action

Built to last a week. Natural amylin survives only minutes in the bloodstream, and the first amylin drug — pramlintide, approved in 2005 — had to be injected at every meal. Cagrilintide is a 37-amino-acid peptide engineered from that same scaffold with two decisive changes: proline substitutions that stop the molecule clumping into amyloid fibrils, and a C20 fatty-diacid side chain that latches onto albumin in the blood. The result is a half-life of 159–195 hours — one injection a week instead of three a day.

Because amylin receptors (AMY1R, AMY2R, AMY3R) and the calcitonin receptor sit outside the GLP-1 pathway, cagrilintide's effect adds to a GLP-1 drug rather than duplicating it. That is the entire logic behind CagriSema, Novo Nordisk's combination of cagrilintide 2.4 mg + semaglutide 2.4 mg — and the trial data below shows the logic works.

The Clinical Evidence

Cagrilintide has one of the deepest evidence bases of any research peptide we carry — a full phase 2 program plus two phase 3 trials published in The New England Journal of Medicine in 2025. The centerpiece is REDEFINE 1: 3,417 adults with overweight or obesity (no diabetes), treated for 68 weeks, with cagrilintide and semaglutide tested alone and together in the same trial.

REDEFINE 1 — Treatment Arm Mean Weight Change, 68 Weeks Notes
CagriSemaCagrilintide 2.4 mg + semaglutide 2.4 mg −20.4% −22.7% among participants who stayed on treatment; ~60% lost at least 20% of body weight.
Semaglutide alone2.4 mg weekly −14.9% The GLP-1 benchmark, beaten head-to-head in the same trial.
Cagrilintide alone2.4 mg weekly −11.5% Double-digit weight loss from the amylin pathway by itself.
PlaceboPlus lifestyle intervention −3.0% 88% of participants with prediabetes on CagriSema returned to normal blood sugar.
−10.8%
Phase 2 monotherapy at 4.5 mg over 26 weeks — beating daily liraglutide (−9.0%). Placebo: −3.0%.
−17.1%
Phase 1b: cagrilintide 2.4 mg + semaglutide in just 20 weeks, vs −9.8% for semaglutide + placebo.
−13.7%
REDEFINE 2 in type 2 diabetes (68 weeks), with 73.5% of participants reaching HbA1c ≤ 6.5%.

The 2026 readouts kept coming. In September 2026, Novo Nordisk reported REIMAGINE 5, a head-to-head in type 2 diabetes: low-dose CagriSema (1.0 mg + 1.0 mg) produced −12.4% weight loss at 60 weeks against −9.1% for tirzepatide 5 mg, with matching blood-sugar control. (Tirzepatide's higher 10 mg and 15 mg doses were not tested in that trial.) In REDEFINE 9, the same 1.0/1.0 mg combination reached −21.0% against −2.0% for placebo at 68 weeks. A higher-dose CagriSema program and a ~7,000-person cardiovascular outcomes trial are also under way.

Reconstitution Basics

Lyophilized (freeze-dried) Cagrilintide must be reconstituted with Bacteriostatic Water (BAC) before research use. Peptopia carries Cagrilintide as a 10 mg vial — the setup below is worked for that vial. Follow these standard sterile handling protocols:

1

Prep & Sanitize 🧼

Wash hands thoroughly. Pop the plastic caps off both the Cagrilintide vial and the BAC water vial. Swab both rubber stoppers with an alcohol prep pad and let air dry.

2

Draw BAC Water 💉

Using a sterile mixing syringe, draw 2.0 mL of Bacteriostatic Water. Added to a 10 mg vial, this yields a concentration of 5 mg per mL — so each 0.1 mL (10 units on a U-100 syringe) equals 0.5 mg.

3

Inject & Dissolve 💧

Pierce the peptide vial. ❗ Do not spray directly onto the powder. Angle the needle so the water runs slowly down the glass wall of the vial to protect the fragile peptide bonds.

4

Swirl Gently 🔄

NEVER SHAKE. Gently roll or swirl the vial between your fingers until the solution is completely clear and dissolved. Refrigerate immediately. At the standard 2.4 mg target dose, one 10 mg vial covers about four weekly doses.

Working with a different vial size or water volume? Run your exact numbers through the Peptopia Reconstitution Calculator, and see our full Reconstitution Guide for sterile technique in depth.

Standard Titration Schedule

The research protocol mirrors the clinical program: a step-up escalation every 4 weeks, injected once every 7 days. The phase 3 target dose is 2.4 mg; the phase 2 program explored doses up to 4.5 mg. Slow escalation is what keeps the GI effects manageable 🤢. Syringe units below are for the 10 mg vial mixed with 2.0 mL BAC water (5 mg/mL).

Timeline Weekly Dose Syringe (U-100) Phase / Notes
Weeks 1 – 4 0.6 mg 12 units Initiation. Acclimate the GI tract; appetite effects begin.
Weeks 5 – 8 1.2 mg 24 units First escalation. Satiety strengthens; the dose used in the early combination studies.
Weeks 9 + 2.4 mg 48 units Phase 3 target dose — the dose behind every REDEFINE result above. Standard maintenance.

In the CagriSema trials, both drugs were started at 0.25 mg and escalated together every 4 weeks, reaching 2.4 mg + 2.4 mg by week 16. Protocols allowed holding or stepping back a dose level whenever tolerability required it — the schedule serves the research, not the other way around.

Side Effects in the Trials

The trial safety picture is dominated by two findings — one expected, one that is cagrilintide's signature:

54.0%
GI events on cagrilintide alone (REDEFINE 1)
73.8%
GI events on semaglutide alone
2.6%
stopped cagrilintide over side effects
16.9%
reported injection-site reactions
GI events — Cagrilintide
54.0%
GI events — Semaglutide
73.8%
Injection-site — Cagrilintide
16.9%
Injection-site — Semaglutide
2.6%

How It Compares

Every compound on this shelf works the appetite system from a different angle. Cagrilintide is the only one that leaves the incretin system alone entirely — it is the amylin pathway, and that is precisely what makes it the natural partner for a GLP-1.

Compound Pathway Headline Trial Result At Peptopia
Cagrilintide Amylin + calcitonin (DACRA) −11.5% alone; −20.4% with semaglutide (REDEFINE 1, 68 wk) 10 mg · $295
Semaglutide GLP-1 −14.9% (REDEFINE 1, 68 wk) 10 mg · $285
Tirzepatide GLP-1 + GIP Low-dose CagriSema beat tirzepatide 5 mg head-to-head in diabetes (−12.4% vs −9.1%, REIMAGINE 5); no full-dose head-to-head yet 30 mg · $395
Retatrutide GLP-1 + GIP + glucagon Triple agonist still in phase 3; never tested head-to-head against cagrilintide 20 mg · $435

Development Status

Cagrilintide is an investigational compound — it is not an approved medicine in any country yet, which is why it is researched rather than prescribed. The combination is closest to the finish line: Novo Nordisk submitted CagriSema to the FDA in December 2025, and a decision is expected in late 2026. Standalone cagrilintide is on its own track — Novo Nordisk has announced a dedicated phase 3 monotherapy program (RENEW) — while the REDEFINE program's cardiovascular outcomes trial continues. Few research compounds arrive with two NEJM phase 3 papers already published; that depth of data is what makes this one worth studying now.

Storage & Handling

Temperature

Store in the refrigerator (36°F to 46°F) both before and after reconstitution. ❗ Do not freeze.

Light Exposure

Peptides are highly sensitive to UV light. Keep vials in their boxes or a dark container.

Shelf Life

Once mixed with BAC water, discard the vial after 28 days to ensure sterility and efficacy.

Sources