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A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment.
J Pharmacokinet Pharmacodyn
January 2025
Department of Clinical Pharmacy and Pharmacy Administration, West China school of Pharmacy, Sichuan University, Chengdu, 610064, China.
Alogliptin is a highly selective inhibitor of dipeptidyl peptidase-4 and primarily excreted as unchanged drug in the urine, and differences in clinical outcomes in renal impairment patients increase the risk of serious adverse reactions. In this study, we developed a comprehensive physiologically-based quantitative systematic pharmacology model of the alogliptin-glucose control system to predict plasma exposure and use glucose as a clinical endpoint to prospectively understand its therapeutic outcomes with varying renal function. Our model incorporates a PBPK model for alogliptin, DPP-4 activity described by receptor occupancy theory, and the crosstalk and feedback loops for GLP-1-GIP-glucagon, insulin, and glucose.
View Article and Find Full Text PDFThe Effects of Glucagon-Like Peptide-1 Receptor Agonists on Mitochondrial Function Within Skeletal Muscle: A Systematic Review.
J Cachexia Sarcopenia Muscle
February 2025
Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester, UK.
Background: Obesity is a chronic disease associated with increased risk of multiple metabolic and mental health-related comorbidities. Recent advances in obesity pharmacotherapy, particularly with glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have the potential to transform obesity and type 2 diabetes mellitus (T2DM) care by promoting marked weight loss, improving glycaemic control and addressing multiple obesity-related comorbidities, with added cardio-renal benefits. Dual agonists combining GLP-1 with other enteropancreatic hormones such as glucose-dependent insulinotropic polypeptide (GIP) have also been developed in recent years, leading to greater weight loss than using GLP-1 RAs alone.
View Article and Find Full Text PDF[Patient with type 2 diabetes and progressive chronic kidney disease].
Rev Med Liege
January 2025
Service de Néphrologie, Dialyse, Transplantation, CHU Liège, Belgique.
Chronic kidney disease (CKD) is a common and severe complication in patients with type 2 diabetes (T2D). While inhibitors of the renin-angiotensin system remained for a long time the only medications that had proven nephroprotective effects, several other pharmacological classes also recently showed such a benefit : sodium-glucose cotransporter type 2 (SGLT2) inhibitors (gliflozins), glucagon-like peptide-1 receptor agonists (semaglutide), and mineralocorticoid receptor antagonists (MRA, finerenone). This clinical vignette aims at explaining the pharmacotherapy strategy for a patient with T2D who presents a progressive CKD.
View Article and Find Full Text PDFGlucagon-like peptide 1 receptor agonists outperform basal insulin in cardiovascular and renal outcomes for type 2 diabetes mellitus: a retrospective cohort study.
Acta Diabetol
January 2025
Division of Cardiology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan.
Purpose: Glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and basal insulin are currently used in the treatment of type 2 diabetes mellitus (T2DM) as long-acting injectables. In this study, we aimed to compare the cardiovascular (CV) and renal outcomes of GLP-1 RAs and basal insulin treatment in patients with T2DM.
Method: We conducted a propensity score-matched cohort study of patients from Chang Gung Memorial Hospital institutions between 2013 and 2021.
[Diabetology : what's new in 2024].
Rev Med Suisse
January 2025
Service d'endocrinologie et diabétologie, Hôpitaux universitaires de Genève, 1211 Genève 14.
Diabetology is a continuously evolving discipline, many molecules are developed, and treatment recommendations change regularly according to the latest published studies. After lifestyle measures that must always be preferred before any drug, metformin remains the pharmacological basis of treatment. Current recommendations favor the introduction of an SGLT2 inhibitor or a GLP-1 receptor agonist after metformin because these molecules have shown beneficial cardiovascular and renal effects.
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