Emerging evidence · Grade B
Cagrilintide
Weight Management
Score
72 / 100
Half-life
~7 days
Class
Amylin analog
Status
Investigational
TL;DR
01
A long-acting amylin analog dosed once weekly, developed by Novo Nordisk primarily as the partner to semaglutide in the combination CagriSema — not yet as a standalone drug.
02
As monotherapy, phase 2 showed about 10.8% weight loss at 26 weeks — modestly better than liraglutide 3 mg, but below semaglutide (~15%) and tirzepatide (~20%+).
03
Combined with semaglutide, phase 3 REDEFINE 1 delivered about 20.4% weight loss at 68 weeks — strong, though below Novo Nordisk's own pre-trial ~25% projection.
04
Main side effects are gastrointestinal, mostly nausea and mostly transient; no drug-related serious adverse events were reported in the monotherapy trials.
05
Investigational: not approved as a standalone in any jurisdiction. The CagriSema combination has completed phase 3 and is under regulatory review.
Wt loss (phase 2, 4.5 mg)
−10.8%
Lancet 2021 · 26 wk monotherapy
vs liraglutide 3 mg
−10.8 vs −9.0%
p=0.03 · phase 2
Combo wt loss (REDEFINE 1)
−20.4%
NEJM 2025 · 68 wk · + semaglutide
Combo phase 1b (peak)
up to −17.1%
Lancet 2021 · 20 wk · + semaglutide
Dosing
Once weekly
~7-day half-life, subcutaneous
Part 01 · How it works
Mechanism.
Cagrilintide is a lab-made, long-lasting version of amylin — a hormone the pancreas releases alongside insulin after a meal to signal fullness. Natural amylin breaks down within minutes; cagrilintide is engineered to last about a week, so a single weekly injection keeps that "I've had enough" signal switched on. It works through a different pathway than the GLP-1 drugs (semaglutide, tirzepatide), which is why pairing the two — as in CagriSema — produces more weight loss than either alone.
If GLP-1 drugs turn down the volume on hunger, amylin turns up the sense of fullness after eating. Cagrilintide is a slow-release version of that fullness signal — and because it pulls a different lever than semaglutide, the two can be stacked.
Amylin receptor agonism
Agonist at amylin receptors (AMY1/AMY3) — the calcitonin receptor coupled with receptor activity-modifying proteins (RAMPs) — in the area postrema and hypothalamus.
Satiety & gastric emptying
Enhances satiety signaling and slows gastric emptying, reducing food intake.
Glucagon suppression
Inhibits postprandial glucagon secretion, contributing to glycemic effects.
Acylation / half-life
Fatty-acid acylation extends the half-life to roughly 159–195 h (~7 days), enabling once-weekly subcutaneous dosing.
Complementarity with GLP-1
A non-overlapping mechanism from incretins, giving additive weight loss when combined with semaglutide (CagriSema).
Part 02 · Dosing & administration
How it's taken.
Clinical · trial-validatedValues below describe how Cagrilintide has been administered in human clinical trials and/or approved labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.
Trial protocol
0.3 → 4.5 mg
Phase 2 escalated over ~6 weeks toward the assigned dose; not a consumer regimen.
TARGET
Combination
2.4 mg
CagriSema trials co-titrated cagrilintide 2.4 mg with semaglutide 2.4 mg.
·
All doses below are values reported in published trials and labeling, not instructions. Cagrilintide is investigational and is not a prescribable product.
·
Trials titrate the dose upward over several weeks specifically to limit gastrointestinal side effects.
·
The studied cadence is once weekly by subcutaneous injection, reflecting the ~7-day half-life.
Need help with reconstitution?
Use the free peptide calculator for dilution, unit conversion, and injection volume.
Part 03 · Safety
Side effects, rare serious events, who shouldn't.
Common
Nausea
Dose-dependent (vs 18% placebo in phase 2); peaks during escalation and usually attenuates.
20–47%
Gastrointestinal disorders (overall)
vs 32% placebo in phase 2; the dominant tolerability issue for the amylin class.
41–63%
Constipation
Part of the GI cluster; individual rate not separately reported in the phase 2 primary publication.
Common
Diarrhea
Reported among GI events; largely mild-to-moderate.
Common
Administration-site reactions
Injection-site pain or redness; generally mild.
Common
Serious · rare
Drug-related serious adverse events
No drug-related serious AEs in the phase 2 or phase 1b trials; discontinuation for adverse events was ~4% in phase 2.
None reported
Gallbladder events
A recognized class consideration with rapid weight loss; not specifically flagged in the cagrilintide monotherapy trials.
Not quantified
Hypoglycemia (in combination)
Not seen with monotherapy; risk rises mainly when combined with insulin or a sulfonylurea.
Low
Absolute · do not use
×
Personal or family history of medullary thyroid carcinoma
×
Multiple endocrine neoplasia syndrome type 2 (MEN2)
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to cagrilintide or any component
×
History of pancreatitis
Relative · discuss first
!
Pregnancy or breastfeeding — no human safety data
!
History of pancreatitis — discuss with GI / endocrinology before any incretin-class or amylin agent
!
Severe gastroparesis or active GI disease — delayed gastric emptying may worsen symptoms
!
Concurrent insulin or sulfonylurea — monitor for hypoglycemia in any combination regimen
!
Anyone seeking a proven standalone therapy — monotherapy evidence stops at phase 2
Interactions
Insulin
Increased risk of hypoglycemia when combined; dose adjustment of insulin may be required
Major
Sulfonylureas (glipizide, glyburide)
Additive hypoglycemic effect; monitor blood glucose and consider dose reduction
Major
Oral medications with narrow therapeutic index
Amylin analogs delay gastric emptying which may affect absorption of oral medications
Moderate
GLP-1 receptor agonists
Additive GI side effects (nausea, vomiting); increased risk of pancreatitis
Moderate
Labs to monitor
Fasting Glucose & Insulin
Baseline and monthly
Monitor glycemic effects
Lipase & Amylase
Baseline and every 3 months
Screen for pancreatitis risk (GLP-1 class concern)
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Liver and kidney function
HbA1c
Baseline and every 3 months
Track glycemic control
Thyroid Panel (TSH, Free T4)
Baseline and every 6 months
Amylin analogues may affect thyroid; class monitoring
Part 04 · Evidence
How strong is the evidence?
72
Grade B
Grade B. The CagriSema combination now has large phase 3 data (REDEFINE 1 & 2), but cagrilintide's own monotherapy evidence stops at phase 2 and no formulation is approved anywhere yet. Rated Emerging as a standalone: the signal is real but the open question is how much the amylin component adds over an established GLP-1 agonist.
Mechanistic plausibility
Amylin biology is well characterized; a durable, once-weekly analog with a mechanism complementary to GLP-1 is a coherent rationale.
85
Human evidence
Phase 2 monotherapy (n=706) plus two large phase 3 combination trials; standalone efficacy has not advanced past phase 2.
78
Safety & tolerability
GI-dominant, mostly transient; no drug-related serious AEs in monotherapy trials, but long-term data are limited.
75
Durability
68-week combination data exist; monotherapy durability and post-treatment regain are not well established.
70
Independence
Essentially all pivotal data are Novo Nordisk-sponsored; no independent replication yet.
55
Part 05 · Research log
Every study we cite.
We list each study with its methodology, funding source, and our quality grade. Flagged studies aren't dismissed — they're tagged so you can weigh them.
01
2021
The Lancet Industry funded
Once-weekly cagrilintide for weight management — dose-finding phase 2 trial
Dose-dependent weight loss of 6.0–10.8% (4.5 mg = 10.8%) vs 3.0% placebo; 4.5 mg beat liraglutide 3 mg (10.8% vs 9.0%, p=0.03). GI adverse events 41–63% vs 32% placebo.
RCT, 26 wk, placebo- and active-controlled (vs liraglutide 3 mg) · n = 706 · Funded by Novo Nordisk; single active comparator; 26-week horizon limits durability read.
PMID 34798060 ↗
High
02
2021
The Lancet Industry funded
Cagrilintide co-administered with semaglutide 2.4 mg — phase 1b combination trial
Combination was well tolerated with an acceptable safety profile; mean weight loss up to ~17.1% at 20 weeks (cagrilintide 2.4 mg + semaglutide), establishing the basis for CagriSema.
Randomized, placebo-controlled, multiple-ascending-dose, 20 wk · n = 96 · Primary endpoint was safety/pharmacokinetics; weight loss was exploratory; small sample and single center.
PMID 33894838 ↗
Moderate
03
2023
The Lancet Industry funded
CagriSema once weekly in type 2 diabetes — phase 2 trial
CagriSema −15.6% weight vs semaglutide −5.1% and cagrilintide −8.1%; HbA1c −2.2 pp with CagriSema. Cagrilintide monotherapy: −8.1% weight, −0.9 pp HbA1c.
RCT, 32 wk, active-controlled (CagriSema vs semaglutide vs cagrilintide) · n = 92 · Funded by Novo Nordisk; small per-arm samples; hypothesis-generating for the phase 3 program.
PMID 37364590 ↗
Moderate
04
2025
New England Journal of Medicine Industry funded
REDEFINE 1 — Coadministered cagrilintide and semaglutide in overweight or obesity
CagriSema −20.4% vs −3.0% placebo (difference −17.3 pp). GI adverse events 79.6% vs 39.9% placebo, mostly transient. The result fell below Novo Nordisk's ~25% pre-trial projection.
Phase 3a RCT, 68 wk, placebo- and active-controlled (incl. cagrilintide-alone and semaglutide-alone arms) · n = 3,417 · Funded by Novo Nordisk; dedicated cagrilintide-alone arm included specifically because monotherapy value was uncertain.
PMID 40544433 ↗
High
05
2025
New England Journal of Medicine Industry funded
REDEFINE 2 — Cagrilintide-semaglutide in overweight/obesity with type 2 diabetes
CagriSema −13.7% vs −3.4% placebo (difference −10.4 pp); 73.5% reached HbA1c ≤6.5%. GI adverse events 72.5% vs 34.4%, mostly mild-to-moderate.
Phase 3a RCT, 68 wk, placebo-controlled · n = 1,206 · Funded by Novo Nordisk; weight effect in T2D smaller than in non-diabetic REDEFINE 1, consistent with the class.
PMID 40544432 ↗
High
Evidence against
What didn't work, and where the evidence is thin.
Every publication is incentivized to tell you a peptide works. We catalogue the null results, failed trials, and mechanism limits we found in the same literature — so you can weigh them against the upside, with your provider.
01
Amylin monotherapy plateaus below the incretin agonists
Mechanism limit Lancet (phase 2) · 2021
At its top phase 2 dose (4.5 mg), cagrilintide produced ~10.8% weight loss over 26 weeks — modestly above liraglutide 3 mg but below semaglutide 2.4 mg (~15%) and tirzepatide (~20%+). Standalone development has not advanced past phase 2.
What this means: As a solo agent, cagrilintide's effect is middling for the current class. Its clearest role is as an add-on to a GLP-1 drug, not a replacement for one.
PMID 34798060 ↗
02
REDEFINE 1 combination undershot expectations and its added value is unsettled
Mechanism limit NEJM (REDEFINE 1) · 2025
Adding cagrilintide to semaglutide gave −20.4% weight loss at 68 weeks — below Novo Nordisk's own ~25% guidance and roughly on par with tirzepatide monotherapy. The trial carried a dedicated cagrilintide-alone arm precisely because the amylin component's contribution was uncertain.
What this means: It remains unclear how much the amylin partner adds over an established GLP-1/GIP agonist used alone. The headline number is strong, but the incremental case for the combination is still being made.
PMID 40544433 ↗
Part 06 · Cost & access
Where it's available, at what price.
United States
Investigational
Not approved. Available only through clinical trials. The CagriSema combination has completed phase 3 (REDEFINE) and is under FDA review.
N/A — no legal consumer product
European Union
Investigational
Not approved as a standalone; CagriSema under regulatory review.
N/A
United Kingdom
Investigational
Not approved; no consumer access outside trials.
N/A
Canada
Investigational
Not approved; no consumer access outside trials.
N/A
The Peptide Column takes no affiliate commission from any source. Cagrilintide is an investigational drug — it is not approved or legally available as a consumer product in any jurisdiction, and the CagriSema combination remains under regulatory review. Any material sold to individuals as "cagrilintide" is unapproved and unregulated.
Part 07 · Your appointment
Questions to bring.
01
How does cagrilintide compare to GLP-1 agonists like semaglutide for weight loss?
02
What are the expected benefits of the CagriSema combination over either drug alone?
03
What gastrointestinal side effects should I expect, and how are they managed?
04
Is cagrilintide appropriate for me given my current medications and health conditions?
References
Every citation, numbered.
Citation list. For our editorial read of each study — including bias flags and quality grades — see the Research log above.
- 01. Once-weekly cagrilintide for weight management — dose-finding phase 2 trial · The Lancet, 2021 · PMID 34798060 ↗
- 02. Cagrilintide co-administered with semaglutide 2.4 mg — phase 1b combination trial · The Lancet, 2021 · PMID 33894838 ↗
- 03.
- 04. REDEFINE 1 — Coadministered cagrilintide and semaglutide in overweight or obesity · New England Journal of Medicine, 2025 · PMID 40544433 ↗
- 05. REDEFINE 2 — Cagrilintide-semaglutide in overweight/obesity with type 2 diabetes · New England Journal of Medicine, 2025 · PMID 40544432 ↗
- 06.
- 07.
- 08.