Cagrilintide: What It Is Studied Alongside

Cagrilintide is a long-acting amylin receptor agonist. It is described in the clinical literature as an amylin analogue under development both as monotherapy for weight management and as a fixed-dose combination with the glucagon-like peptide-1 receptor agonist semaglutide, a combination referred to as CagriSema [4]. The evidence block supplied for this page does not give a sequence, molecular formula or molecular weight for the compound, so none is stated here. The identifiers available are trial registration numbers: NCT07745504, NCT07607587, NCT07605052, NCT07597018 and NCT07557953, each corresponding to a registered human study of cagrilintide [1][5][6][7][8].

The work centres on the amylin receptor, a heterodimeric complex built from the calcitonin receptor (Calcr) and a receptor activity-modifying protein, with Calcr/Ramp3 populations in the dorsal vagal complex identified as mediators of cagrilintide action in cross-species transcriptomic mapping [3].

Research Studies

Cagrilintide and Calcr-expressing dorsal vagal complex neurons

A cross-species atlas of the dorsal vagal complex was generated to identify neural mediators of cagrilintide's effects on energy balance. The atlas comprised transcriptomic data from over 530,000 cells, covering 80 neuronal cell populations across rat, mouse and macaque caudal brainstem, with spatial profiling used to map distribution in the rat dorsal vagal complex [3].

Two conserved Calcr-expressing dorsal vagal complex neuronal populations were found to be regulated by cagrilintide. Acute treatment altered gene expression in area postrema Calcr/Ramp3 neurons, but chemogenetic activation of those neurons in rats did not affect long-term food intake or body weight. Long-term cagrilintide treatment in rats produced a different pattern, with upregulation reported in the same study [3]. This is a rodent and non-human primate dataset; the chemogenetic manipulation was performed in rats only.

Cagrilintide and semaglutide as a fixed-dose combination (CagriSema)

The most frequently studied pairing is cagrilintide with semaglutide. The rationale given in the clinical literature is that the amylin receptor agonist and the GLP-1 receptor agonist have complementary effects on glycaemic control and body weight [11]. CagriSema has been evaluated in adults with type 2 diabetes inadequately controlled on diet and exercise in a randomised, double-blind, placebo-controlled phase 3a study (REIMAGINE 1) [10], and against semaglutide or cagrilintide alone in a double-blind, randomised, controlled phase 3 study in people with type 2 diabetes (REIMAGINE 2) [11]. A further paper describes cagrilintide-semaglutide as a new option for patients with type 2 diabetes [12]. These are reference sources for this page rather than its subject matter; they are cited here for what they report.

Cagrilintide and tirzepatide, semaglutide and CagriSema in network meta-analysis

No direct head-to-head studies have compared all advanced anti-obesity medications, so a network meta-analysis was conducted to examine comparative efficacy and safety. The authors systematically searched PubMed, Scopus and Cochrane Central and included tirzepatide, semaglutide, cagrilintide and their combination, CagriSema [2]. The analysis is framed around a population of adults with overweight and obesity; obesity is described in that paper as a chronic, progressive disease affecting over 1 billion adults worldwide and linked to diabetes, hypertension and cardiovascular disease [2].

Cagrilintide and amylin-based therapy versus placebo

A systematic review and meta-analysis evaluated amylin-based obesity therapy, covering cagrilintide and CagriSema versus placebo. Cagrilintide is described in that work as a once-weekly amylin receptor agonist, and CagriSema as its fixed-dose combination with semaglutide [9]. This is a reference source for the present page; the finding reported is that the review assessed these agents against placebo in the context of obesity as a global health challenge [9].

Cagrilintide and renal or hepatic impairment

Two studies assessed the effect of renal or hepatic impairment on the pharmacokinetics, safety and tolerability of subcutaneous cagrilintide. Adult participants were categorised into four groups by renal or hepatic function — normal function and mild, moderate or severe impairment — and received a single dose of cagrilintide 0.6 or 0.9 (units as reported in the source) [4]. The stated conclusion of that work is that renal or hepatic impairment does not affect the pharmacokinetics, safety or tolerability of subcutaneous cagrilintide [4]. The population was adults with impaired or normal renal or hepatic function, not a general obesity cohort.

Cagrilintide and GLP-1 receptor agonist intolerance

A registered study is evaluating the tolerability of cagrilintide specifically in participants who do not tolerate marketed GLP-1 therapies because of gastrointestinal adverse events. Participants live with overweight or obesity and are randomised to cagrilintide or placebo, with the study lasting about 8 months [5]. This is a safety-focused study design; the evidence block does not report results.

Cagrilintide and food intake and appetite in humans

A separate registered study is testing cagrilintide to understand how it affects food intake and appetite in people with overweight or obesity. Participants receive cagrilintide or placebo, with a study duration of about 30 weeks [8]. The stated purpose is mechanistic — food intake and appetite — rather than a comparison against another active compound.

Cagrilintide and formulation comparisons: version B versus version D

Several registered studies compare different versions of cagrilintide rather than cagrilintide against another drug class. One compares blood levels of two versions, cagrilintide B and cagrilintide D, in adults with excess body weight over about 14 weeks [6]. A second compares blood levels after multiple doses of the same two versions in adults with overweight or obesity over about 6 months [7]. A third compares two different versions of injectable cagrilintide and placebo in people with excess body weight, with participants in the study for about 9 months [1].

Cagrilintide and the boundaries of the current evidence

Where the evidence supplied for this page is animal-only, it is labelled as such. The dorsal vagal complex atlas work was conducted in rat, mouse and macaque tissue, with chemogenetic activation performed in rats [3]. The human material consists of registered study protocols and their stated purposes, plus a network meta-analysis of randomised clinical trials [1][2][5][6][7][8]. No in vitro data are supplied in the evidence block for this page, and none is claimed. Cagrilintide is described in one source as a new medicine under development that doctors cannot prescribe yet, though it has been tested in humans before [1].

If you are reading this for personal health reasons

This material is sold for laboratory research only, and we do not provide dosing or medical guidance. Anyone considering a compound for themselves should speak to a licensed clinician. Nothing on this page is a recommendation for human use.

Sources

• [1] A Research Study to Compare Two Different Versions of Injectable Cagrilintide and Placebo in People With Excess Body Weight — https://clinicaltrials.gov/study/NCT07745504
• [2] Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials — https://europepmc.org/article/PMC/PMC13239642
• [3] A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance — https://europepmc.org/article/PMC/PMC13303089
• [4] Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide — https://europepmc.org/article/PMC/PMC13356073
• [5] Evaluation of the Tolerability of Cagrilintide in Participants Not Tolerating GLP-1-RA Therapies Due to Gastrointestinal Adverse Events — https://clinicaltrials.gov/study/NCT07607587
• [6] A Research Study to Compare Blood Levels of Two Different Versions of Cagrilintide in Adults With Excess Body Weight — https://clinicaltrials.gov/study/NCT07605052
• [7] A Research Study to Compare Blood Levels of Cagrilintide After Multiple Doses of Different Versions of Cagrilintide in Adults With Overweight or Obesity — https://clinicaltrials.gov/study/NCT07597018
• [8] A Research Study Looking Into How Cagrilintide Influences Food Intake and Appetite in People With Overweight or Obesity — https://clinicaltrials.gov/study/NCT07557953
• [9] Amylin-based obesity therapy: a meta-analysis of Cagrilintide and CagriSema versus placebo — https://europepmc.org/article/PMC/PMC13461105
• [10] Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1) — https://pubmed.ncbi.nlm.nih.gov/42251860/
• [11] Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2) — https://pubmed.ncbi.nlm.nih.gov/42251859/
• [12] Cagrilintide-semaglutide: a new option for patients with type 2 diabetes — https://pubmed.ncbi.nlm.nih.gov/42251858/