Core Viewpoint - GLP-1 receptor agonists and co-agonists, initially developed for type 2 diabetes treatment, have expanded benefits including weight loss and reduced incidence of chronic diseases such as cardiovascular disease, chronic kidney disease, and metabolic dysfunction-related fatty liver disease [2][3][27]. Summary by Sections GLP-1 Class Drugs Overview - GLP-1 drugs like liraglutide, dulaglutide, semaglutide, and tirzepatide enhance insulin secretion, reduce glucagon secretion, and slow gastric emptying, contributing to weight loss and appetite suppression [2]. - These drugs have been approved for treating type 2 diabetes and obesity, with additional benefits in reducing chronic kidney disease, myocardial infarction, stroke, and cardiovascular mortality [2]. Clinical Evidence and Expanding Benefits - Daniel J. Drucker's article highlights the benefits of GLP-1 drugs beyond diabetes and obesity, including cardiovascular disease, chronic kidney disease, metabolic dysfunction-related fatty liver disease, osteoarthritis, obstructive sleep apnea, and peripheral artery disease [3]. Cardiovascular and Kidney Disease - Semaglutide received FDA approval in 2024 as the first weight loss drug proven to reduce major adverse cardiovascular events in adults with obesity or overweight and established cardiovascular disease [7]. - In clinical trials, semaglutide significantly reduced the incidence of non-fatal myocardial infarction and stroke, with a risk ratio of 0.8 compared to placebo [7]. - In patients with heart failure with preserved ejection fraction (HFpEF), semaglutide improved symptoms and reduced cardiovascular death and heart failure-related events by 31% [10]. Metabolic Dysfunction-Related Fatty Liver Disease - In a clinical trial involving 1,200 adults with metabolic dysfunction-associated steatotic liver disease (MASH), semaglutide improved liver histology and increased the rate of fatty liver resolution [13]. - The benefits of semaglutide may be secondary to weight loss or improvements in liver metabolism and inflammation [13]. Osteoarthritis - The STEP 9 trial showed that semaglutide treatment significantly reduced pain scores in patients with knee osteoarthritis and resulted in greater weight loss compared to placebo [17]. Obstructive Sleep Apnea - The SURMOUNT-OSA trial demonstrated that tirzepatide significantly reduced the apnea-hypopnea index in adults with moderate to severe obstructive sleep apnea [19]. Peripheral Artery Disease - The STRIDE trial indicated that semaglutide improved walking distance in patients with peripheral artery disease, correlating with weight loss [21]. Neuroprotective Effects - GLP-1 drugs have been associated with reduced stroke incidence and may lower the risk of all-cause dementia, including Alzheimer's disease [23]. - Ongoing trials are exploring the potential of oral semaglutide in modifying Alzheimer's disease [23]. Mechanisms of Action - The exact mechanisms by which GLP-1 drugs provide benefits independent of weight loss remain unclear, but they may involve improvements in insulin sensitivity and inflammation reduction [25][26]. - GLP-1 drugs consistently lower inflammatory biomarkers, suggesting immune-modulating effects that may contribute to their therapeutic benefits [26]. Conclusion and Future Directions - The broad benefits of GLP-1 drugs extend to various chronic conditions, with ongoing research exploring their applications in substance abuse, mental health, and neurodegenerative diseases [27]. - Understanding the dose-response relationship and optimal treatment duration for conditions beyond diabetes and obesity may open new therapeutic avenues for GLP-1 drugs [27].