A long-acting amylin receptor agonist used for obesity and type 2 diabetes treatment by enhancing satiety, reducing food intake, and aiding weight loss.
Larsen. A T AT; Mohamed. K E KE; Sonne. N N; Bredtoft. E E; Andersen. F F; Karsdal. M A MA; Henrikse...
Both cagrilintide and a similar peptide called KBP-336 activate the same two receptors that control appetite and metabolism, but KBP-336 leans more toward the calcitonin receptor. In rats, this bias makes KBP-336 cause slightly more weight loss and better blood‑sugar control than cagrilintide, especially at higher doses.
Bailey. Clifford J CJ; Flatt. Peter R PR; Conlon. J Michael JM
The abstract says that long‑acting peptide drugs that mimic gut hormones (like GLP‑1 and GIP) can dramatically lower blood sugar and help people lose weight. Semaglutide, a GLP‑1 drug you can take as a pill or injection, works even better when paired with another peptide called cagrilintide. Other new peptides that hit multiple hormone receptors (e.g., tirzepatide) also show strong results, but many of these are still in clinical trials.
Caruso. Irene I; Cignarelli. Angelo A; Sorice. Gian Pio GP; Perrini. Sebastio S; Giorgino. Francesco...
The paper reviews how drugs that mimic gut hormones—like GLP‑1, GIP and glucagon—help people lose weight and improve health. It notes that approved drugs (liraglutide, semaglutide, tirzepatide) and newer combos such as cagrilintide + semaglutide (CagriSema) can cut body weight by at least 5% in many users and lower the risk of diabetes, heart problems, knee arthritis, sleep apnea, and fatty liver disease. The benefits seem to come from both the direct drug actions and the weight‑loss they cause.
Abdalla Ahmed. Mohammed Altigani MA; Ssemmondo. Emmanuel E; Mark-Wagstaff. Charlotte C; Sathyapalan....
This review talks about the growing obesity problem and lists the drugs we already have, like orlistat and GLP‑1 agonists, plus new candidates such as cagrilintide that are showing strong weight‑loss results in early studies. It stresses that any drug plan should be personalized and done with a doctor’s guidance.
De. Riddhita R; Prasad. Femin F; Stogios. Nicolette N; Burin. Luisa L; Ebdrup. Bjørn H BH; Knop...
People with severe mental illness often gain weight because of the medicines they take, and the usual weight‑loss drugs only help a little. This review points out that a new peptide called cagrilintide (often combined with semaglutide) looks promising for cutting weight in this group, based on studies in the general population.
Bailey. Clifford J CJ; Flatt. Peter R PR; Conlon. J Michael JM
The review talks about the newest wave of peptide drugs that hit several hormone receptors at once. One of the most interesting combos is semaglutide (a GLP‑1 drug) paired with cagrilintide, an amylin‑like peptide, called CagriSema. These multi‑target peptides are shown to lower blood sugar, cut weight, and may also help heart, kidney, liver, and even brain health, but most of the data are still from early trials.
This review explains that the hormone amylin and its drug version cagrilintide act on many brain regions to make you feel full, and that combining cagrilintide with the popular weight‑loss drug semaglutide can boost fat loss, though you may need to watch for side‑effects like nausea.
Al Lawati. Abdullah A; Alhabsi. Ayman A; Rahul. Rhieya R; Savino. Maria-Luisa ML; Alwahaibi. Hamed H...
This review talks about the drugs currently used to lose weight, especially injections that hit the GLP‑1 system, which work better than pills. It also points out that newer compounds like cagrilintide look promising, but they’re still being studied. Side effects are mostly stomach‑related, and while AI could someday help tailor weight‑loss plans, it isn’t ready for everyday use yet.
Hadid. Somar S; Frishman. William H WH; Aronow. Wilbert S WS
The article explains that diabetes and obesity often go hand‑in‑hand and that current drugs like GLP‑1 agonists and amylin analogs help both conditions, but tight blood‑sugar control can cause dangerous low‑sugar episodes. A new experimental combo called CagriSema (cagrilintide + semaglutide) looks promising for lowering blood‑sugar and weight with fewer side effects, though real‑world data are still limited.
This review talks about new obesity drugs that work like the hormone GLP‑1. It lists many experimental compounds, including a combo of cagrilintide with semaglutide, and notes that semaglutide is the most advanced and will likely set the standard for future treatments.
Fletcher. Madeleine M MM; Keov. Peter P; Truong. Tin T TT; Mennen. Grace G; Hick. Caroline A CA; Zha...
The study shows that cagrilintide (AM833) is a new peptide that activates both calcitonin and amylin receptors, and it performed better than some older drugs in lab tests and early human trials for weight loss. While it isn’t on the market yet, the data suggest it could become a useful tool for managing obesity and related metabolic issues.
Lima. Luís Maurício T R LMTR; Icart. Luis Peña LP
The review warns that peptide drugs like cagrilintide can clump together into larger, inactive forms (amyloid or amorphous aggregates) if they aren't stored, handled, or formulated correctly. These clumps can reduce the drug’s effectiveness and may trigger immune reactions, so paying attention to stability is crucial for anyone using these peptides outside a clinical setting.
Gu. Yi-Min YM; Yuan. Qing-Ning QN; Li. Xin X; He. Qian Q; Xu. H Eric HE; Zhao. Li-Hua LH
The study shows how the weight‑loss peptide cagrilintide binds to two different receptors (amylin and calcitonin) in a similar way, using specific parts of the molecule to lock onto the receptors and turn on the same signaling pathway. This explains why the drug works on both targets and may help design better versions.
Martínez-Castelao. Alberto A; Górriz. José Luis JL; Fernández-Fernández. Be...
The abstract reviews the drugs that are currently used to protect kidneys in diabetes and outlines new medicines that are being tested, including cagrilintide, which is grouped with next‑generation GLP‑1‑type drugs. While it doesn’t give new trial data on cagrilintide, it signals that this peptide may soon be part of the toolbox for weight loss, blood‑sugar control, and kidney protection.
A new weekly injection called semaglutide (2.4 mg) can help people lose a lot of weight and improve health problems linked to obesity. It works better than older weight‑loss drugs, but surgery still gives the biggest results. The abstract also mentions that even newer drugs like tirzepatide and cagrilintide might cause even more weight loss than semaglutide, pointing to a shift toward using powerful drugs to manage diabetes and obesity.
Carvas. Alexandra Oliveira AO; Leuthardt. Andrea A; Kulka. Patricia P; Lommi. Greta G; Hassan. Shad...
Amylin (AmyR) and calcitonin (CTR) receptor co-agonists are currently in Phase II/III clinical trials for obesity treatment. Amylin binds to a heterodimeric receptor composed of CTR and the receptor activity modifying proteins 1, 2 or 3 (RAMP1-3).
We investigated the role of amylin 1 and 3 (AMY<sub>1</sub>R, AMY<sub>3</sub>R) receptors in modulating the pharmacological effects of the dual amylin-calcitonin receptor agonists, cagrilintide and salmon calcitonin (sCT), in RAMP1/3 knockout (KO) mice. Male wild-type (WT) and KO littermate mice were fed high-fat diet for 23 weeks prior to the 3-week treatment period with vehicle, 150 nmol/kg sCT or 3 nmol/kg cagrilintide (subcutaneously, SID).
Body weight loss was observed in WT cagrilintide-treated mice (-3.4 ± 0.51 g, P < 0.005; n = 8/group), whereas sCT rather increased it (0.60 ± 0.38 g, P < 0.01; n = 8/group). The absence of RAMP1 and RAMP3 impeded cagrilintide's potency but improved sCT's efficacy on weight loss. Cagrilintide and sCT both decreased food intake during the first few days of treatment in WT mice only (Day 1: vehicle 2.7 ± 0.2 g; cagrilintide 1.2 ± 0.1 g, P < 0.0001; sCT 1.5 ± 0.2 g, P < 0.0021; n = 7-8/group). Both peptides activated cFos signal in neurons of the dorsal vagal complex (DVC) and lateral parabrachial nucleus (LPBN) of WT mice while AP cFos signal was decreased in cagrilintide-treated RAMP1/3 KO mice by 57% compared to WT cagrilintide-injected mice (P < 0.001, n = 5-6/group). Differential gene expression was analysed in the DVC, LPBN and mediobasal hypothalamic area of WT and RAMP1/3 KO mice. After 3 weeks of treatment, neither sCT nor cagrilintide significantly altered gene expression in the DVC or LPBN in WT mice. However, mRNA bulk sequencing points to a role of RAMP1/3 in synaptic function and receptor trafficking.
Altogether, these results demonstrate the dependency of cagrilintide on AMY<sub>1</sub>R and AMY<sub>3</sub>R to lower body weight.
This work was supported by an investigator led Novo Nordisk Consortium grant, Swiss National Foundation and the University of Zurich.
Gabery. Sanaz S; Glendorf. Tine T; Ballarin-Gonzalez. Borja B; Pedersen. Kent K; Kruse. Thomas T; Ra...
Cagrilintide (also known as 0833) is an amylin and calcitonin receptor agonist in clinical development for weight management and type-2-diabetes in a fixed-dose combination with semaglutide. Here, we introduce 0174-0839 (0839) as a tool compound for mouse and rat in vivo and in vitro studies of amylin analogues such as cagrilintide. Structurally, 0839 shares 95 % sequence homology with 0833 and contains an identical acylation sidechain. Acute administration of 0839 and 0833 to normal weight rats' dose-dependently reduced food intake to a similar degree. Sub-chronically, 0839 and 0833 had comparable small and transient reducing effects on food intake and body weight in DIO mice, with similar additional add-on effects on top of semaglutide. In DIO rats, sub-chronic administration of 0833 and 0839 profoundly reduced food intake and body weight, and both potentiated semaglutide's effects on food intake and body weight to an equal extended. Both compounds mainly reduced body weight by fat mass reduction and equally improved metabolic parameters. Notably, 0839 is available through Novo Nordisk Compound Sharing, enabling advancement of mode-of-action studies in mice and rats whilst usage of cagrilintide and other amylin analogues in clinical development are restricted due to pharmacovigilance rules.
Cao. Jianjun J; Belousoff. Matthew J MJ; Johnson. Rachel M RM; Keov. Peter P; Mariam. Zamara Z; Dega...
Obesity is a major and increasingly prevalent chronic metabolic disease with numerous comorbidities. While recent incretin-based therapies have provided pharmaceutical inroads into treatment of obesity, there remains an ongoing need for additional medicines with distinct modes of action as independent or complementary therapeutics. Among the most promising candidates, supported by phase 1 and 2 clinical trials, is cagrilintide, a long-acting amylin and calcitonin receptor agonist. As such, understanding how cagrilintide functionally engages target receptors is critical for future development of this target class. Here, we determine structures of cagrilintide bound to Gs-coupled, active, amylin receptors (AMY<sub>1</sub>R, AMY<sub>2</sub>R, AMY<sub>3</sub>R) and calcitonin receptor (CTR) and compare cagrilintide interactions and the dynamics of receptor complexes with previously reported structures of receptors bound to rat amylin, salmon calcitonin or recently developed amylin-based peptides. These data reveal that cagrilintide has an amylin-like binding mode but, compared to other peptides, induces distinct conformational dynamics at calcitonin-family receptors that could contribute to its clinical efficacy.
Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate the suppression of food intake and body weight. To understand the molecular and neural mechanisms of cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across the rat, mouse, and non-human primate caudal brainstem. We then integrated spatial profiling to reveal neuron distribution in the rat DVC. Furthermore, we compared the acute and long-term transcriptional responses to cagrilintide across DVC neurons of rats, which exhibit strong cagrilintide responsiveness, and mice, which respond poorly to cagrilintide over the long term. We found that cagrilintide promoted long-term transcriptional changes, including increased prolactin releasing hormone (<i>Prlh)</i> expression, in the nucleus of the solitary tract (NTS) <i>Calcr/Prlh</i> cells in rats, but not in mice, suggesting the importance of NTS <i>Calcr/Prlh</i> cells for sustained weight loss. Indeed, activating rat area postrema <i>Calcr</i> cells briefly reduced food intake but failed to decrease food intake or body weight over the long term. Overall, these results not only provide a cross-species and spatial atlas of DVC cell populations but also define the molecular and neural mediators of acute and long-term cagrilintide action.