Glucagon-like Peptide-1 Receptor Agonists as an Approach to Modestly Slow Aging
Semaglutide is probably the best known of the glucagon-like peptide-1 receptor agonists, a class of drug deployed to treat type 2 diabetes and other consequences of obesity. This is one of a number of classes of diabetes drug where there is some suspicion that maybe these small molecules can modestly slow aging through much the same set of mechanisms that help to steer the abnormal metabolism of obesity and diabetes into a modestly less terrible state, e.g. reduced blood glucose and inflammatory signaling. Equally, the data to support that belief is far from compelling, and the effect sizes are small in comparison to, say, those produced by exercise. An equally plausible explanation for observed effects is that drugs that promote weight loss and lower calorie intake operate through the well studied mechanisms of calorie restriction and reduced impact of visceral fat.
Increased age is associated with frailty and diseases of varying severities, 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 introduction of 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 prolonged healthspan for more people across the world, novel pharmacotherapeutics and optimal use of existing options are arguably needed.
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an example of a drug class with proven or potential benefits across a range of prevalent age-related conditions and complications. 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 research and clinical use of the drug class has led to the initiation of clinical trials with GLP-1 RAs in other prominent aging-related diseases, including chronic kidney disease (CKD) and Alzheimer's disease. In sum, GLP-1 RAs are positioned 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.