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What is Cagrilintide?

Cagrilintide is a long-acting amylin receptor agonist studied as a monotherapy and in fixed-dose combination with semaglutide. This page summarises its identity, receptor pathway, and the clinical and preclinical researc

peptides-pro Editorial

Cagrilintide is a long-acting amylin receptor agonist developed for weight management, both as a monotherapy and as a fixed-dose combination with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, a combination referred to as CagriSema [4]. It is described in the clinical literature as a once-weekly amylin receptor agonist [9]. The evidence block used for this page does not provide a sequence, molecular formula, or molecular weight for cagrilintide, so those identifiers are not stated here.

The research on cagrilintide centres on the amylin receptor pathway, a calcitonin receptor (Calcr)-based receptor system expressed in the dorsal vagal complex of the caudal brainstem, where cagrilintide has been shown to regulate Calcr-expressing neuronal populations [3].

Research Studies

Cagrilintide and amylin receptor agonism in the dorsal vagal complex

A cross-species transcriptomics study generated an atlas of over 530,000 cells comprising 80 neuronal cell populations across rat, mouse, and macaque caudal brainstem, with spatial profiling to map distribution in the rat dorsal vagal complex (DVC) [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 in rats did not affect long-term food intake and body weight. In contrast, long-term cagrilintide treatment in rats was reported to upregulate a separate population, and the study identified neural mediators of cagrilintide's effects on energy balance [3]. This work is animal-based and does not establish human mechanisms.

Cagrilintide and pharmacokinetics in renal or hepatic impairment

Two studies assessed the effects of renal or hepatic impairment on the pharmacokinetics, safety, and tolerability of subcutaneous cagrilintide following single doses [4]. Adult participants were categorised into four groups on the basis of 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. The study reported that renal or hepatic impairment did not affect the pharmacokinetics, safety, or tolerability of subcutaneous cagrilintide [4].

Cagrilintide and food intake and appetite in people with overweight or obesity

A clinical 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 assignment decided by chance, and the study lasts about 30 weeks. The stated purpose is to examine the effect of cagrilintide on food intake and appetite in this population [8].

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

A clinical study is evaluating the safety of cagrilintide compared with placebo in people who do not tolerate marketed GLP-1 therapies and who live with overweight or obesity [5]. Participants receive either cagrilintide or placebo, with assignment decided by chance, and the study lasts about 8 months. The study population is specifically those with gastrointestinal adverse events on GLP-1 receptor agonist therapies [5].

Cagrilintide and comparison of two injectable versions in people with excess body weight

A clinical study is comparing two different versions of injectable cagrilintide and placebo in people with excess body weight [1]. Participants receive cagrilintide, the active study medicine, or placebo, with assignment decided by chance, and are in the study for about 9 months. The study notes that cagrilintide is a new medicine under development that doctors cannot prescribe yet, but it has been tested in humans before [1].

Cagrilintide and blood levels of two versions in adults with excess body weight

A clinical study is comparing two different versions of cagrilintide and how they work in people living with excess body weight [6]. Participants receive either cagrilintide B or cagrilintide D injections, with assignment decided by chance, and are in the study for about 14 weeks. The stated purpose is to compare blood levels of the two versions [6].

Cagrilintide and blood levels after multiple doses of different versions

A clinical study is testing two versions of cagrilintide to compare their effects in participants with overweight or obesity [7]. Participants receive either cagrilintide version D or version B, with assignment decided by chance, and are in the study for about 6 months. The stated purpose is to compare blood levels of cagrilintide after multiple doses of the different versions [7].

Cagrilintide and comparative effectiveness in overweight and obesity

A network meta-analysis examined the comparative efficacy and safety of tirzepatide, semaglutide, cagrilintide, and their combination (CagriSema) in the management of overweight and obesity [2]. The authors noted that obesity is a chronic, progressive disease affecting over 1 billion adults worldwide, linked to serious comorbidities including diabetes, hypertension, and cardiovascular disease and associated with increased mortality, and that achieving clinically meaningful weight loss is critical to reducing cardiometabolic risk. The analysis stated that no direct head-to-head studies had compared all advanced anti-obesity medications, and it systematically searched PubMed, Scopus, and Cochrane Central for randomised clinical trials [2].

Cagrilintide and amylin-based obesity therapy versus placebo

A systematic review and meta-analysis evaluated amylin-based obesity therapy, specifically cagrilintide and CagriSema versus placebo [9]. The authors described cagrilintide as a once-weekly amylin receptor agonist and its fixed-dose combination with semaglutide (CagriSema) as novel therapeutic approaches, and evaluated the evidence in the context of 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 randomised, double-blind, placebo-controlled, phase 3a study assessed the efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise [10]. The study described CagriSema as a novel, once-weekly combination of the amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide [10].

The REIMAGINE 2 double-blind, randomised, controlled, phase 3 study investigated the efficacy and safety of a fixed-dose combination of cagrilintide and semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes [11]. The authors noted that the amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide have complementary effects on glycaemic control and bodyweight [11].

A further publication described cagrilintide-semaglutide as a new option for patients with type 2 diabetes [12].

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