速递｜GLP-3类减重药横空出世！礼来三重激动机制或超越肥胖手术

Core Viewpoint - The article discusses the evolution of weight loss and metabolic treatment drugs, highlighting the transition from GLP-1 receptor agonists like Semaglutide to the dual agonist Tirzepatide, and now to the triple agonist Retatrutide, which represents a significant advancement in the treatment of obesity and metabolic diseases [5][8][12]. Group 1: GLP-1 and Tirzepatide - Semaglutide, originally developed for type 2 diabetes, has gained popularity as a weight loss drug, demonstrating significant weight reduction and additional cardiovascular and renal protective effects [5]. - Tirzepatide, known as a "second-generation miracle drug," is the first GLP-1/GIP dual agonist, showing enhanced effects on weight loss and lipid metabolism, particularly beneficial for high-risk cardiovascular patients [5][6]. - Clinical trials indicate that Tirzepatide may provide kidney protection comparable to or better than Semaglutide [5][8]. Group 2: Introduction of GLP-3 - Retatrutide, a candidate in phase III clinical trials, represents a new class of GLP-3 drugs that act on three key metabolic hormone receptors, enhancing appetite suppression and energy expenditure [6][9]. - The mechanism of GLP-3 drugs allows for a more comprehensive approach to weight loss, combining appetite suppression with increased energy expenditure, moving beyond the traditional "eat less" strategy [7][9]. Group 3: Clinical Data and Potential - Early and mid-stage clinical studies of Retatrutide show significant weight loss and improvements in insulin sensitivity and metabolic markers, with effects comparable to metabolic surgery [8][9]. - In obese populations, Retatrutide's weight loss is approaching that of surgical interventions, and it demonstrates superior reductions in key atherosclerotic indicators compared to existing drugs [9]. Group 4: Kidney Function and Safety - A study on Retatrutide's effects on overweight or obese individuals with chronic kidney disease suggests potential renal benefits, with some participants showing improved kidney function and reduced urinary albumin excretion [10]. - The ongoing research aims to clarify Retatrutide's long-term effects on kidney health, particularly concerning its impact on renal hemodynamics and potential protective mechanisms [10][11]. Group 5: Future Implications - The transition from Semaglutide to Tirzepatide and now to Retatrutide signifies a fundamental shift in metabolic treatment logic, focusing on comprehensive metabolic reprogramming rather than just glucose control or weight loss [12]. - If Retatrutide fulfills its potential in clinical trials, it could herald a new era in the treatment of metabolic diseases, integrating weight loss, glycemic control, and lipid management into a single therapeutic approach [12].