Semaglutide Weight Management and Cardiovascular Risk Reduction

GLP-1 RAs have proven positive effects beyond glycaemic control in T2D and may hold further potential Glucagon-like peptide-1 receptor agonists to expand the healthy lifespan: Current and future potentials Frederik Flindt Kreiner | Bernt Johan von Scholten | Peter Kurtzhals | Stephen Charles Langford Gough Global Medical Affairs, Novo Nordisk A/S, Søborg. Denmark Correspondence Stephen Charles Langford Gough, Global Medical Affairs, Novo Nordisk A/S, Søborg, Denmark. Email: [email protected] Abstract To help ensure an expanded healthy lifespan for as many people possible world- wide, there is a need O prevent or manage a number of prevalent chronic diseases directly and indirectly closely related to aging, including diabetes and obesity. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have proven beneficial in type 2 diabetes, are amongst the few medicines approved for weight management, and are also licensed for focused cardiovascular risk reduction. In addition, strong evi- dence suggests several other beneficial effects of the pleiotropic peptide hormone, including anti-inflammation. Consequently, GLP-1 RAS are now in advanced clinical development for the treatment of chronic kidney disease, broader cardiovascular risk reduction, metabolic liver disease and Alzheimer's disease. In sum, GLP-1 RAS are po sitioned as one of the pharmacotherapeutic options that can contribute to addressing the high unmet medical need characterising several prevalent aging-related diseases, potentially helping more people enjoy a prolonged healthy lifespan. KEYWORDS Alzheimer's disease, cardiovascular diseases, chronic kidney diseases, diabetes mellitus, glucagon-like peptide-1, healthy aging, non-alcoholic steatohepatitis, obesity 1 INTRODUCTION Increased age is associated with trailty and diseases of varying sever- ities, and for many, the hope of a long and healthy lifespan therefore becomes elusive. Nevertheless, overall life expectancy has increased markedly during the past decades, owing to a large extent to the in- troduction medicines such as statins and anti-hypertensives. These and newer generation drugs have resulted in a lower prevalence and severity of age-related illnesses such as cardiovascular disease (CVD) To sustain and reinforce this positive trend and help ensure a pro- longed healthspan for more people across the world, novel pharmaco- therapeutics and optimal use of existing options are arguably needed. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are ample of a drug class with proven or potential benefits across a range of prevalent age-related conditions and complications (Müller et al., 2019). Originally developed to manage blood glucose levels in type 2 diabetes (T2D), GLP-1 RAs have subsequently been confirmed to have marked benefits on body weight and CVD risk. Furthermore, evidence from Abbreviation CHIP, clonal haematopoiesis of indeterminate potential CKD, chronic kidney disease; CVD, cardiovascular CVOT, cardiovascular outcomes trial; DKD, diabetic kidney disease, DM, diabetes mellitus: GP, gastric inhibitory peptide GLP-1, glucagon-like peptide-1: GLP-1R glucagon-like peptide-1 receptor, HFPEF, heart failure with preserved ejection fraction; MACE major adverse cardiovascular event; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic hepatocteatosis; RA, receptor agonist: T2D, type 2 diabetes. This is an open access and _ is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in provided the original work is properly cited. © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. any medium, Proven GLP-1 RA effects in T2D Glycaemic control Weight loss CV risk reduction Hypothesized GLP-1 RA effects GD Chronic kidney disease Alzheimer's disease GLP-1 RA: Glucagon like peptide-1 receptor agonist; T2D: Type 2 diabetes; CV: Cardiovascular Metabolic liver syndrome Peripheral artery disease

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