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Hedi Raizer

Journal 6 min read

Cagrilintide: what the published research shows

A research summary of cagrilintide, a long-acting amylin receptor agonist studied as monotherapy and in fixed-dose combination with semaglutide, covering its receptor pharmacology, cross-species brainstem mapping, pharma

peptides-pro Editorial

Cagrilintide is a long-acting amylin receptor agonist developed as a once-weekly subcutaneous agent, studied both as monotherapy for weight management and as a fixed-dose combination with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, a combination referred to as CagriSema [4]. The published record describes it as a new medicine under development that doctors cannot prescribe, and one that has already been tested in humans [1]. The identifiers most often attached to the molecule in the literature are its class (amylin analogue), its receptor target (the amylin receptor, a calcitonin receptor/RAMP heterodimer), and its dosing interval (once weekly) [4][9].

The work centres on amylin receptor signalling, and specifically on calcitonin receptor (Calcr)-expressing neuronal populations in the caudal brainstem, where cagrilintide has been shown to regulate two conserved cell populations in the dorsal vagal complex [3].

Research Studies

Cagrilintide and Calcr-expressing dorsal vagal complex neurons

A cross-species transcriptomic atlas covering more than 530,000 cells and 80 neuronal cell populations across rat, mouse and macaque caudal brainstem, with spatial profiling in the rat dorsal vagal complex (DVC), was generated to identify mediators of cagrilintide action [3]. The study reported that cagrilintide regulates two conserved Calcr-expressing DVC neuronal populations. Acute cagrilintide 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. By contrast, long-term cagrilintide treatment in rats produced effects on the second population examined [3]. This is animal and cross-species work; the cell-level findings are not human outcomes.

Cagrilintide and pharmacokinetics in renal or hepatic impairment

Two studies assessed the effect of renal or hepatic impairment on the pharmacokinetics, safety and tolerability of single subcutaneous doses of cagrilintide [4]. 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 mg [4]. The reported conclusion was that renal or hepatic impairment did not affect the pharmacokinetics, safety or tolerability of subcutaneous cagrilintide [4].

Cagrilintide and food intake and appetite in overweight or obesity

A dedicated study is testing cagrilintide to understand how it affects food intake and appetite in people with overweight or obesity [8]. Participants receive either cagrilintide or placebo, with allocation decided by chance, and the study runs for about 30 weeks [8]. This is a mechanistic appetite and intake study rather than a body-weight endpoint study.

Cagrilintide and tolerability in people not tolerating GLP-1 receptor agonists

A separate study examines the safety of cagrilintide compared with placebo in people who do not tolerate marketed GLP-1 therapies because of gastrointestinal adverse events and who live with overweight or obesity [5]. Participants receive cagrilintide or placebo, allocation is by chance, and the study lasts about 8 months [5]. The population here is defined by prior GLP-1 intolerance, which distinguishes it from general overweight or obesity cohorts.

Cagrilintide and comparison of two injectable versions in excess body weight

A study compares two different versions of injectable cagrilintide against placebo in people with excess body weight, with participants randomised to cagrilintide or placebo and followed for about 9 months [1]. A related study compares blood levels of two different versions of cagrilintide in adults with excess body weight, in which participants receive either cagrilintide B or cagrilintide D injections, with allocation decided by chance, over about 14 weeks [6]. A further study compares blood levels of cagrilintide after multiple doses of different versions in adults with overweight or obesity, again using cagrilintide version D or version B, over about 6 months [7].

StudyPopulationComparisonDuration
NCT07745504 [1]Excess body weightTwo injectable cagrilintide versions vs placeboAbout 9 months
NCT07605052 [6]Excess body weightCagrilintide B vs cagrilintide DAbout 14 weeks
NCT07597018 [7]Overweight or obesityCagrilintide version D vs version B, multiple dosesAbout 6 months
NCT07557953 [8]Overweight or obesityCagrilintide vs placebo (food intake and appetite)About 30 weeks
NCT07607587 [5]Overweight or obesity with GLP-1 intoleranceCagrilintide vs placeboAbout 8 months

Cagrilintide and comparative efficacy across advanced anti-obesity medications

A network meta-analysis examined the comparative efficacy and safety of tirzepatide, semaglutide, cagrilintide and their combination (CagriSema), noting that no direct head-to-head studies had compared all advanced anti-obesity medications [2]. The authors systematically searched PubMed, Scopus and Cochrane Central for randomised clinical trials [2]. The analysis is a network comparison rather than a direct trial, and its estimates are indirect for several of the pairwise contrasts.

Cagrilintide and amylin-based therapy versus placebo

A systematic review and meta-analysis evaluated amylin-based obesity therapy, covering cagrilintide as a once-weekly amylin receptor agonist and its fixed-dose combination with semaglutide (CagriSema), against placebo [9]. The review frames obesity as a major global health challenge driving demand for effective pharmacotherapies [9].

Cagrilintide-semaglutide and glycaemic control in type 2 diabetes

The REIMAGINE 1 phase 3a randomised, double-blind, placebo-controlled study assessed the efficacy and safety of once-weekly cagrilintide-semaglutide in adults with type 2 diabetes inadequately controlled on diet and exercise [10]. The REIMAGINE 2 double-blind, randomised, controlled phase 3 study compared cagrilintide-semaglutide with semaglutide or cagrilintide alone in people with type 2 diabetes, on the basis that the amylin receptor agonist and the GLP-1 receptor agonist have complementary effects on glycaemic control and bodyweight [11]. A further commentary describes cagrilintide-semaglutide as a new option for patients with type 2 diabetes [12]. These findings concern the fixed-dose combination, not cagrilintide as a single agent.

If you are reading this for personal health reasons

This material is sold for laboratory research use only, and we do not provide dosing or medical guidance of any kind. Nothing here is a recommendation to use cagrilintide or any related compound in a person. Anyone considering a compound for themselves should speak to a licensed clinician.

Sources

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