Explore studies of next gen agonists.
Amylin and pramlintide increased amyloid-beta production by modulating APP and γ-secretase in lipid rafts, leading to increased Aβ burden, synaptic loss, and neuroinflammation in TgSwDI Alzheimer's mice.
Mousa, Youssef M; Abdallah, Ihab M; Hwang, Misako; Martin, Douglas R; Kaddoumi, Amal · Animal
Cagrilintide 2.4 mg plus semaglutide 2.4 mg achieved 17.1% body weight reduction at 20 weeks, with an estimated treatment difference of -7.4% versus semaglutide plus placebo (95% CI -11.2 to -3.5). No pharmacokinetic interactions between the drugs.
Enebo, Lone B; Berthelsen, Kasper K; Kankam, Martin; Lund, Michael T; Rubino, Domenica M; Satylganova, Altynai; Lau, David C W · Randomized Controlled Trial (Phase 1b)
AM833 (cagrilintide) is a nonselective agonist with a unique pharmacological profile across 25 endpoints of receptor binding, activation, and regulation compared to 5 other selective and nonselective AMYR/CTR agonists including pramlintide and salmon calcitonin.
Fletcher, Madeleine M; Keov, Peter; Truong, Tin T; Mennen, Grace; Hick, Caroline A; Zhao, Peishen; Furness, Sebastian G B; Kruse, Thomas; Clausen, Trine R; Wootten, Denise; Sexton, Patrick M · In Vitro (Pharmacology)
Pramlintide induced headache in 88% and migraine-like attacks in 41% of patients (vs CGRP: 97% and 56%, differences not significant). The effects were mediated through amylin receptors, not the canonical CGRP receptor. Animal models confirmed amylin causes cutaneous hypersensitivity and light aversion.
Ghanizada, Hashmat; Al-Karagholi, Mohammad Al-Mahdi; Walker, Christopher S; Arngrim, Nanna; Rees, Tayla; Petersen, Jakeb; Siow, Andrew; Mørch-Rasmussen, Mette; Tan, Sheryl; O'Carroll, Simon J; Harris, Paul; Skovgaard, Lene Theil; Jørgensen, Niklas Rye; Brimble, Margaret; Waite, Jayme S; Rea, Brandon J; Sowers, Levi P; Russo, Andrew F; Hay, Debbie L; Ashina, Messoud · Randomized Controlled Trial (Crossover) + Animal
15+ GLP-1-based compounds in clinical obesity development: mono-GLP-1 (semaglutide, PF-0688296, glutazumab), dual (tirzepatide, cotadutide, efinopegdutide, AMG 133), and multi-receptor (CagriSema, HM15211). Semaglutide positioned as the clinical benchmark.
Jepsen, Mathies M; Christensen, Mikkel B · Review
Pramlintide with insulin reduces HbA1c and weight with minimal/no hypoglycemia in T1DM and T2DM. Mechanisms: delayed gastric emptying, glucagon suppression, appetite reduction. Cardiovascular safety appears favorable. Shares mechanisms with GLP-1 RAs.
Koshy, Rithika Mary; Fernandez, Cornelius James; Jacob, Koshy · Review
Researchers developed cagrilintide, a stable, lipidated long-acting amylin analogue that overcomes two major challenges of native amylin: its tendency to form amyloid fibrils and its very short half-life. Unlike pramlintide (the only approved amylin analogue), which requires three daily injections, cagrilintide's lipidation strategy enables once-weekly dosing. Cagrilintide has induced significant weight loss in clinical trials both when used alone and when combined with the GLP-1 analogue semaglutide. The paper details the structure-activity relationship studies that led to selecting cagrilintide (compound 23) from a series of candidates for clinical development with obesity as the primary indication.
Kruse, Thomas; Hansen, Jakob Lerche; Dahl, Kirsten; Schäffer, Lauge; Sensfuss, Ulrich; Poulsen, Christian; Schlein, Morten; Hansen, Ann Maria Kruse; Jeppesen, Claus Bekker; Dornonville de la Cour, Charlotta; Clausen, Trine Ryberg; Johansson, Eva; Fulle, Simone; Skyggebjerg, Rikke Bjerring; Raun, Kirsten · Preclinical
Proglucagon-derived peptide family includes glucagon, GLP-1, GLP-2, oxyntomodulin, glicentin, and GRPP. Each has distinct biology and therapeutic applications. GLP-1 dominates current therapeutics, while oxyntomodulin and glucagon combinations are emerging.
Lafferty, Ryan A; O'Harte, Finbarr P M; Irwin, Nigel; Gault, Victor A; Flatt, Peter R · Review