The Journal of Clinical Psychiatry, Год журнала: 2024, Номер 85(2)
Опубликована: Июнь 3, 2024
Язык: Английский
Diabetes Care, Год журнала: 2024, Номер unknown
Опубликована: Июнь 6, 2024
The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits GLP-1RA in select patient populations. In ongoing trials investigators are interrogating efficacy these agents new indications, including metabolic liver disease, peripheral artery Parkinson Alzheimer disease. success GLP-1–based medicines has spurred molecular entities combinations with unique pharmacokinetic pharmacodynamic profiles, exemplified tirzepatide, a GIP-GLP-1 coagonist. Simultaneously, investigational molecules such as maritide block GIP activate GLP-1 receptor, whereas retatrutide survodutide enable simultaneous activation glucagon receptors. Here I highlight evidence medicines, while discussing that inform safety, focusing on muscle strength, bone density fractures, exercise capacity, gastrointestinal motility, retained gastric contents anesthesia, pancreatic biliary tract disorders, risk cancer. Rapid progress highly efficacious anticipated differentiation newer subsets will provide greater opportunities use personalized medicine approaches to improve health people living cardiometabolic disorders.
Язык: Английский
Процитировано
99
Cell Metabolism, Год журнала: 2023, Номер 35(9), С. 1519 - 1529
Опубликована: Авг. 16, 2023
Язык: Английский
Процитировано
62
Science, Год журнала: 2024, Номер 385(6706), С. 258 - 260
Опубликована: Июль 18, 2024
Glucagon-like peptide–1–based medicines have weight loss–independent actions
Язык: Английский
Процитировано
57
Cell, Год журнала: 2024, Номер 187(15), С. 3789 - 3820
Опубликована: Июль 1, 2024
Язык: Английский
Процитировано
56
The Lancet Diabetes & Endocrinology, Год журнала: 2024, Номер 12(8), С. 545 - 557
Опубликована: Июль 8, 2024
Процитировано
45
Nature Metabolism, Год журнала: 2024, Номер 6(10), С. 1866 - 1885
Опубликована: Авг. 19, 2024
The introduction of the highly potent incretin receptor agonists semaglutide and tirzepatide has marked a new era in treatment type 2 diabetes obesity. With normalisation glycated haemoglobin levels weight losses around 15-25%, therapeutic goals that were previously unrealistic are now within reach, clinical trials have documented these effects associated with reduced risk cardiovascular events premature mortality. Here, I review this remarkable development from earliest observations glucose lowering modest native glucagon-like peptide (GLP)-1 short acting compounds, to recent active formulations molecules. will classify agents as GLP-1-based therapies understanding compounds or combinations may actions on other receptors well. physiology GLP-1 is discussed well its mechanisms obesity, particular, role sensory afferents brain. provide details regarding for anti-obesity therapy discuss possible mechanism behind their beneficial adverse events. Finally, highlight pharmacological developments, including oral agents, important questions maintenance therapy.
Язык: Английский
Процитировано
26
Cell Metabolism, Год журнала: 2024, Номер 36(2), С. 338 - 353
Опубликована: Янв. 9, 2024
Язык: Английский
Процитировано
23
Endocrine, Год журнала: 2024, Номер 84(3), С. 822 - 835
Опубликована: Март 12, 2024
Abstract Purpose Chronic kidney disease (CKD) is one of the most common complications type 2 diabetes (T2D), and CKD-related disability mortality are increasing despite recent advances in management. The dual GIP/GLP-1 receptor agonist tirzepatide among furthest developed multi-agonists for care has so far displayed promising nephroprotective effects. This review aims to summarize evidence regarding effects glucagon-like peptide-1 agonists (GLP-1RA) putative mechanisms underlying favorable renal profile tirzepatide. Methods A comprehensive literature search was performed from inception July 31st 2023 select research papers addressing GLP-1RA Results pathogenesis CKD patients with T2D likely involves many contributors besides hyperglycemia, such as hypertension, obesity, insulin resistance glomerular atherosclerosis, exerting damage through metabolic, fibrotic, inflammatory, hemodynamic mechanisms. Tirzepatide an unprecedented glucose body weight lowering potential, presenting also ability increase sensitivity, reduce systolic blood pressure inflammation ameliorate dyslipidemia, particularly by reducing triglycerides levels. Conclusion counteract pathogenetic factors contributing T2D, potentially representing a step forward incretin-based therapy towards nephroprotection. Further needed understand its role hemodynamics, fibrosis, cell well conclusively show reduction hard outcomes.
Язык: Английский
Процитировано
20
Nature, Год журнала: 2025, Номер 639(8055), С. 708 - 716
Опубликована: Фев. 5, 2025
Abstract The hypothalamus is a brain region that plays key role in coordinating fundamental biological functions 1 . However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies 2,3 Here we combine single-nucleus sequencing 433,369 human hypothalamic cells with spatial transcriptomics, generating comprehensive spatio-cellular transcriptional map hypothalamus, ‘HYPOMAP’. Although conservation neuronal cell types between humans mice, as based on transcriptomic identity, generally high, there are notable exceptions. Specifically, significant disparities identity pro-opiomelanocortin neurons expression levels G-protein-coupled receptors two species carry direct implications for currently approved obesity treatments. Out 452 types, find 291 clusters significantly enriched body mass index (BMI) genome-wide association study genes. This enrichment driven by 426 ‘effector’ Rare deleterious variants six these ( MC4R , PCSK1 POMC CALCR BSN CORO1A ) associate BMI at population level, has not been linked previously to BMI. Thus, HYPOMAP provides detailed atlas context serves an important resource identify new druggable targets treating wide range conditions, including reproductive, circadian metabolic disorders.
Язык: Английский
Процитировано
8
Comprehensive physiology, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 1, 2025
ABSTRACT Humans are perhaps evolutionarily engineered to get deeply addicted sugar, as it not only provides energy but also helps in storing fats, which survival during starvation. Additionally, sugars (glucose and fructose) stimulate the feel‐good factor, they trigger secretion of serotonin dopamine brain, associated with reward sensation, uplifting mood general. However, when consumed excess, contributes imbalance, weight gain, obesity, leading onset a complex metabolic disorder, generally referred diabetes. Type 2 diabetes mellitus (T2DM) is one most prevalent forms diabetes, nearly affecting all age groups. T2DM clinically diagnosed cardinal sign chronic hyperglycemia (excessive sugar blood). Chronic hyperglycemia, coupled dysfunctions pancreatic β‐cells, insulin resistance, immune inflammation, further exacerbate pathology T2DM. Uncontrolled T2DM, major public health concern, significantly toward progression several micro‐ macrovascular diseases, such diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, cardiovascular including cancer. The current review discusses epidemiology, causative factors, pathophysiology, comorbidities, existing emerging therapies related It future roadmap for alternative drug discovery management
Язык: Английский
Процитировано
3