Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities

Peptides, Journal Year: 2025, Volume and Issue: 187, P. 171380 - 171380

Published: March 11, 2025

Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and dual tirzepatide that engages receptors for GLP-1 glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials 'real-world' confirmed marked glucose-lowering weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young elderly individuals without diabetes and/or overweight or obesity. also protections against development progression cardiovascular renal diseases are additive to benefits conferred by improved control blood glucose body weight. Emerging evidence suggests therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea possibly degenerative bone disorders cognitive decline. New incretin-based peptide in a long-acting glucagon (LY3324954), GLP-1/glucagon agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon (retatrutide, efocipegtrutide), combination amylin analogue cagrilintide (CagriSema), unimolecular GLP-1/amylin (amycretin), GIP antibody agonism (MariTide). The creation multi-targeting synthetic peptides provides opportunities management type 2 obesity as well new therapeutic approaches an expanding list associated co-morbidities. aim review is acquaint reader developments field from 2023 present (February 2025).

Language: Английский

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The NLRP3 inhibitor NT‐0796 enhances and sustains GLP‐1R agonist‐mediated weight loss in a murine diet‐induced obesity model

Obesity, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Abstract Objective In order to investigate whether a central nervous system penetrant anti‐inflammatory could augment or sustain obesity treatment with semaglutide (Wegovy), glucagon‐like peptide‐1 receptor (GLP‐1R) agonist, we tested two hypotheses in models of diet‐induced (DIO): 1) centrally NLPR3 inhibitor, NT‐0796, drives enhanced weight loss when combined low‐dose semaglutide, compared monotherapy; and 2) NT‐0796 monotherapy sustains induced by semaglutide. Methods Mice fed standard high‐fat polyunsaturated fatty acid diet served as DIO were dosed combinations. Body weight, food intake, peripheral inflammatory markers, hypothalamic glial fibrillary acidic protein expression assessed. Results Combined dosing drove greater than either alone, this effect was mice consuming the diet. addition, sharply limited regain following cessation therapy normalized markers both inflammation astrogliosis far extent calorie restriction. Conclusions Alleviation obesity‐associated via NLRP3 inhibition constitutes an effective weight‐loss strategy DIO, augments efficacy subtherapeutic dose 3) blocks recovery lost image

Language: Английский

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Central nervous system pathways targeted by amylin in the regulation of food intake

Biochimie, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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