, an anorexic hormone, is deficient in diabetes and is associated with improved glycemic control when supplemented with pramlintide.
Amylin plays a role in regulating blood sugar levels after meals and may also have cardiovascular and protective effects on the brain.
Deficiencies in amylin are linked to hormonal imbalances in diabetes, which could contribute to complications in managing the disease.
Pramlintide, the only approved injectable amylin analog, has shown efficacy in enhancing blood sugar control in type 1 and type 2 diabetes without increasing hypoglycemia risk or weight gain.
Research is examining methods to improve amylin's stability and delivery, including potential oral formulations and combination therapies targeting multiple metabolic pathways.
The combination of a glucagon-like peptide-1 receptor agonist with an amylin agonist shows promise for better glucose regulation and weight management.
Simplified
Precision diabetology is increasingly becoming diabetes phenotype-driven, whereby the specific hormonal imbalances involved are taken into consideration. Concomitantly, body weight-favorable therapeutic approaches are being dictated by the obesity pandemic, which extends to all diabetes subpopulations. , an anorexic neuroendocrine hormone co-secreted with insulin, is deficient in individuals with diabetes and plays an important role in postprandial glucose homeostasis, with additional potential cardiovascular and neuroprotective functions. Its actions include suppressing glucagon secretion, delaying gastric emptying, increasing energy expenditure and promoting satiety. While amylin holds promise as a therapeutic agent, its translation into clinical practice is hampered by complex receptor biology, the limitations of animal models, its amyloidogenic properties and pharmacokinetic challenges. In individuals with advanced β-cell dysfunction, supplementing insulin therapy with pramlintide, the first and currently only approved injectable short-acting selective analog of amylin, has demonstrated efficacy in enhancing both postprandial and overall glycemic control in both type 2 diabetes (T2D) and type 1 diabetes (T1D) without increasing the risk of hypoglycemia or weight gain. Current research focuses on several key strategies, from enhancing amylin stability by attaching polyethylene glycol or carbohydrate molecules to amylin, to developing oral amylin formulations to improve patients' convenience, as well as developing various combination therapies to enhance weight loss and glucose regulation by targeting multiple receptors in metabolic pathways. The novel synergistically acting glucagon-like peptide-1 (GLP-1) receptor agonist combined with the amylin agonist, CagriSema, shows promising results in both glucose regulation and weight management. As such, amylin agonists (combined with other members of the incretin class) could represent the elusive drug candidate to address the multi-hormonal dysregulations of diabetes subtypes and qualify as a precision medicine approach that surpasses the long overdue division into T1DM and T2DM. Further development of amylin-based therapies or delivery systems is crucial to fully unlock the therapeutic potential of this intriguing hormone.Graphical abstract available for this article.
Key numbers
17.1%
Weight Loss with Cagrilintide
Weight loss percentage after 20 weeks of treatment.
7.9%
Weight Loss with
Placebo-corrected weight loss after 12 months.
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Declarations. Conflict of Interest: All authors have given lectures, received honoraria and research support and participated in conferences, advisory boards and clinical trials sponsored by many pharmaceutical companies. However, no pharmaceutical company played any role in the scientific content of the present article, which has been written independently and reflects only the opinions of the authors, without no imput from the pharmaceutical industry. The following conflict of interests are reported. Špela Volčanšek has received lecture honoraria from Novo Nordisk, Eli Lilly, Medtronic, Abbott, AstraZeneca and Boehringer Ingelheim. Andrijana Koceva reports receiving lecture honoraria from Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Medtronic and Pfizer. Mojca Jensterle has received lecture honoraria from Novo Nordisk, Eli Lilly, Pfizer, Amgen, Novartis and Sanofi, and is an advisory board member of Novo Nordisk, Eli Lilly, Amgen and Pfizer. Andrej Janež has served as a consultant and is on Speakers Bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Medtronic, Abbott, Novo Nordisk, Novartis and Swixx. Emir Muzurović has given lectures and participated in conferences and advisory boards sponsored by several pharmaceutical companies, including Novo Nordisk, Sanofi, AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Medtronic and Servier. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
