Peptide Protocol IQ
InvestigationalHuman evidence

Cagrilintide

Also referred to as AM833

An investigational amylin analogue studied alone and in combination with semaglutide. Combination programme readouts continue to evolve.

Molecule class
Long-acting amylin analogue
Category
Amylin
Last evidence review
2026-08-23
5
Human studies
0
Animal / in vitro
1
Graded claims
5,421
Participants

Derived from qualifying human evidence

  • Most commonly studied duration: 68 weeks. Most frequently reported duration among 4 qualifying human studies with a stated duration.
  • Longest qualifying human study: 68 weeks. Longest duration among qualifying human studies with a stated duration.

These figures are computed from the study records shown below. Records without a verified source identifier are excluded from the calculation.

Mechanism

What is being studied

Agonises amylin and calcitonin receptors, contributing to satiety signalling through a pathway distinct from the incretin receptors.

Evidence

Claims, graded individually

Each statement below carries its own evidence level, its own confidence rating, and its own account of what remains unestablished. A compound does not have a single grade.

Metabolic & Body-Composition Research

CPreliminaryLow confidenceHuman evidence

Cagrilintide, alone and combined with semaglutide, has been studied for weight reduction in randomised trials.

What is not established

Programme readouts have been revised. Verify the specific trial and arm before relying on any figure.

Supporting sources (5)
Randomised controlled trialHuman Identifier verified

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)

Garvey WT, Blüher M, Osorto Contreras CK, et al. · New England Journal of Medicine · 2025 · n = 3,417

Population
Adults with BMI ≥30, or ≥27 with at least one obesity-related complication; without type 2 diabetes
Endpoint
Percentage change in body weight to week 68, and the proportion achieving at least 5% reduction
Route
Subcutaneous
Quantity as reported
Cagrilintide 2.4 mg with semaglutide 2.4 mg, each once weekly, reached by week 16 from a 0.25 mg start with steps every 4 weeks
Frequency
Once weekly
Duration
68 weeks

Result. Body weight changed by −20.4% with the combination versus −3.0% with placebo on the treatment-policy estimand, a difference of −17.3 percentage points. Semaglutide alone reached −14.9% and cagrilintide alone −11.5% in the same trial.

Adverse events. Gastrointestinal events predominated and were most frequent during escalation, consistent with both drug classes.

Limitations. Excluded type 2 diabetes. The widely quoted −22.7% figure is the trial-product estimand, which models full adherence, and is not the primary result. Sixty-eight weeks says nothing about what happens on discontinuation.

Randomised controlled trialHuman Identifier verified

Cagrilintide and Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)

Davies MJ, et al.; REDEFINE 2 Study Group · New England Journal of Medicine · 2025 · n = 1,206

Population
Adults with overweight or obesity and type 2 diabetes, across 12 countries
Endpoint
Percentage change in body weight to week 68, and the proportion achieving at least 5% reduction
Route
Subcutaneous
Quantity as reported
Cagrilintide 2.4 mg with semaglutide 2.4 mg, each once weekly, escalated 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg at 4-week steps
Frequency
Once weekly
Duration
68 weeks

Result. Body weight changed by −13.7% versus −3.4% with placebo, a difference of −10.4 percentage points. The effect is materially smaller than in the population without diabetes.

Adverse events. Gastrointestinal events consistent with the incretin and amylin classes.

Limitations. The gap between this result and REDEFINE 1 is the finding worth carrying: the same schedule in a diabetic population produced roughly two-thirds of the weight change.

Randomised controlled trialHuman Identifier verified

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

Frias JP, Deenadayalan S, Erichsen L, et al. · The Lancet · 2023 · n = 92

Population
Adults with type 2 diabetes, BMI ≥27, on metformin with or without an SGLT2 inhibitor
Endpoint
Change in HbA1c from baseline to week 32
Route
Subcutaneous
Quantity as reported
Cagrilintide 2.4 mg with semaglutide 2.4 mg, each once weekly after escalation
Frequency
Once weekly
Duration
32 weeks

Result. HbA1c fell 2.2 percentage points with the combination versus 1.8 with semaglutide alone, which did not reach significance. Body weight fell 15.6% versus 5.1% and 8.1%, which did.

Adverse events. Gastrointestinal, dose-escalation related.

Limitations. Ninety-two participants across three arms. This is the dose-ranging ancestor of the phase 3 programme, not a basis for practice.

Randomised controlled trialHuman Identifier verified

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

Lau DCW, Erichsen L, Francisco AM, et al. · The Lancet · 2021 · n = 706

Population
Adults with overweight or obesity without diabetes, across 57 sites
Endpoint
Percentage change in body weight to week 26
Route
Subcutaneous
Quantity as reported
Cagrilintide 0.3, 0.6, 1.2, 2.4 or 4.5 mg once weekly, escalated in steps every 2 weeks to the assigned final amount
Frequency
Once weekly
Duration
26 weeks

Result. Weight change ranged from −6.0% at 0.3 mg to −10.8% at 4.5 mg, against −3.0% for placebo. The 4.5 mg arm beat liraglutide 3.0 mg at −9.0%.

Adverse events. Gastrointestinal events, dose related.

Limitations. This is the only trial that establishes what cagrilintide does on its own. Note that the amount taken forward into the combination programme was 2.4 mg, not the 4.5 mg that performed best here.

Randomised controlled trialHumanIdentifier pending verification

Cagrilintide and cagrilintide/semaglutide combination trials

Multiple · The Lancet and New England Journal of Medicine programmes · 2023

Population
Adults with overweight or obesity
Endpoint
Percentage change in body weight
Route
Subcutaneous
Quantity as reported
Reported per registered trial arm
Frequency
Once weekly
Duration
68 weeks

Result. The amylin analogue alone and in combination with semaglutide reported greater weight reduction than semaglutide alone in the programmes reported.

Adverse events. Gastrointestinal events consistent with the incretin/amylin classes.

Limitations. Verify the specific trial and arm before citing a figure. Combination programmes are ongoing and readouts continue to change.

Last evidence review: 2026-08-23

Human evidence

5 human studies catalogued

Human and non-human evidence are kept strictly separate. They are never pooled, averaged, or presented as a single body of support.

Randomised controlled trialHumanIdentifier pending verification

Cagrilintide and cagrilintide/semaglutide combination trials

Multiple · The Lancet and New England Journal of Medicine programmes · 2023

Population
Adults with overweight or obesity
Endpoint
Percentage change in body weight
Route
Subcutaneous
Quantity as reported
Reported per registered trial arm
Frequency
Once weekly
Duration
68 weeks

Result. The amylin analogue alone and in combination with semaglutide reported greater weight reduction than semaglutide alone in the programmes reported.

Adverse events. Gastrointestinal events consistent with the incretin/amylin classes.

Limitations. Verify the specific trial and arm before citing a figure. Combination programmes are ongoing and readouts continue to change.

Randomised controlled trialHuman Identifier verified

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)

Garvey WT, Blüher M, Osorto Contreras CK, et al. · New England Journal of Medicine · 2025 · n = 3,417

Population
Adults with BMI ≥30, or ≥27 with at least one obesity-related complication; without type 2 diabetes
Endpoint
Percentage change in body weight to week 68, and the proportion achieving at least 5% reduction
Route
Subcutaneous
Quantity as reported
Cagrilintide 2.4 mg with semaglutide 2.4 mg, each once weekly, reached by week 16 from a 0.25 mg start with steps every 4 weeks
Frequency
Once weekly
Duration
68 weeks

Result. Body weight changed by −20.4% with the combination versus −3.0% with placebo on the treatment-policy estimand, a difference of −17.3 percentage points. Semaglutide alone reached −14.9% and cagrilintide alone −11.5% in the same trial.

Adverse events. Gastrointestinal events predominated and were most frequent during escalation, consistent with both drug classes.

Limitations. Excluded type 2 diabetes. The widely quoted −22.7% figure is the trial-product estimand, which models full adherence, and is not the primary result. Sixty-eight weeks says nothing about what happens on discontinuation.

Randomised controlled trialHuman Identifier verified

Cagrilintide and Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)

Davies MJ, et al.; REDEFINE 2 Study Group · New England Journal of Medicine · 2025 · n = 1,206

Population
Adults with overweight or obesity and type 2 diabetes, across 12 countries
Endpoint
Percentage change in body weight to week 68, and the proportion achieving at least 5% reduction
Route
Subcutaneous
Quantity as reported
Cagrilintide 2.4 mg with semaglutide 2.4 mg, each once weekly, escalated 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg at 4-week steps
Frequency
Once weekly
Duration
68 weeks

Result. Body weight changed by −13.7% versus −3.4% with placebo, a difference of −10.4 percentage points. The effect is materially smaller than in the population without diabetes.

Adverse events. Gastrointestinal events consistent with the incretin and amylin classes.

Limitations. The gap between this result and REDEFINE 1 is the finding worth carrying: the same schedule in a diabetic population produced roughly two-thirds of the weight change.

Randomised controlled trialHuman Identifier verified

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

Frias JP, Deenadayalan S, Erichsen L, et al. · The Lancet · 2023 · n = 92

Population
Adults with type 2 diabetes, BMI ≥27, on metformin with or without an SGLT2 inhibitor
Endpoint
Change in HbA1c from baseline to week 32
Route
Subcutaneous
Quantity as reported
Cagrilintide 2.4 mg with semaglutide 2.4 mg, each once weekly after escalation
Frequency
Once weekly
Duration
32 weeks

Result. HbA1c fell 2.2 percentage points with the combination versus 1.8 with semaglutide alone, which did not reach significance. Body weight fell 15.6% versus 5.1% and 8.1%, which did.

Adverse events. Gastrointestinal, dose-escalation related.

Limitations. Ninety-two participants across three arms. This is the dose-ranging ancestor of the phase 3 programme, not a basis for practice.

Randomised controlled trialHuman Identifier verified

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

Lau DCW, Erichsen L, Francisco AM, et al. · The Lancet · 2021 · n = 706

Population
Adults with overweight or obesity without diabetes, across 57 sites
Endpoint
Percentage change in body weight to week 26
Route
Subcutaneous
Quantity as reported
Cagrilintide 0.3, 0.6, 1.2, 2.4 or 4.5 mg once weekly, escalated in steps every 2 weeks to the assigned final amount
Frequency
Once weekly
Duration
26 weeks

Result. Weight change ranged from −6.0% at 0.3 mg to −10.8% at 4.5 mg, against −3.0% for placebo. The 4.5 mg arm beat liraglutide 3.0 mg at −9.0%.

Adverse events. Gastrointestinal events, dose related.

Limitations. This is the only trial that establishes what cagrilintide does on its own. Note that the amount taken forward into the combination programme was 2.4 mg, not the 4.5 mg that performed best here.

Pharmacology

Reported parameters

Half-life

7.5 days

Reported to support once-weekly administration.

Visualise this half-life →

Routes studied

  • Subcutaneous

Evidence from one route does not transfer to another. Topical, oral, and injected administration can produce entirely different exposure from the same quantity.

Regulatory status

Investigational. Not approved.

Storage as documented

No approved storage labelling exists for this investigational compound.

Safety

Signals reported in the literature

This lists what has been reported. It is not a complete safety profile, and for several compounds in this catalogue no systematic safety surveillance exists at all.

  • Gastrointestinal events reported, particularly in combination
  • Long-term safety not established

Limitations

What the evidence cannot tell you

Given as much prominence as the findings, because for most compounds in this category it is the more important half.

  • Trial arms and reported figures differ substantially between programmes — verify the specific arm before citing any number
  • Combination readouts have been revised as programmes reported

Reference

Evidence grading key

AStrong

Multiple high-quality human trials, or strong systematic-review or meta-analytic evidence.

BModerate

Human controlled evidence exists, but replication or sample size is limited.

CPreliminary

Small human studies, observational evidence, or early-phase clinical work.

DPreclinical

Predominantly animal or in-vitro evidence. No adequate human outcome data.

EMechanistic

Biological plausibility or mechanistic reasoning without adequate outcome evidence.

XInsufficient / conflicting

Evidence is absent, irreconcilable, or too weak to support any directional statement.

Related

Other compounds studied in the same research areas