Core Viewpoint - The article discusses the significant advancements in GLP-1 receptor agonists over the past 20 years, highlighting their transformative impact on the treatment of metabolic diseases, particularly diabetes and obesity, and their potential for broader clinical applications [3][4][6]. Group 1: Development and Mechanism of GLP-1 Receptor Agonists - GLP-1 receptor agonists have evolved from a niche discovery to a cornerstone in clinical treatment, with their development rooted in the identification of GLP-1's insulinotropic properties [4][6]. - The scientific foundation of GLP-1 receptor agonists dates back to the 1960s, with key discoveries revealing the biological mechanisms that enhance insulin secretion through GLP-1 receptor activation [6][7]. - Recent studies, such as the SELECT trial, demonstrate that GLP-1 receptor agonists significantly reduce cardiovascular risks, establishing their role beyond glucose control [7][9]. Group 2: Clinical Benefits and Applications - GLP-1 receptor agonists provide multiple benefits, including cardiovascular protection, weight management, and organ protection, making them essential in managing metabolic syndrome [4][8]. - The drugs exhibit a glucose-dependent insulin secretion mechanism, which minimizes the risk of hypoglycemia, and have shown efficacy in weight loss and cardiovascular health [13][12]. - New formulations, including long-acting and oral versions, are being developed to enhance patient compliance and treatment outcomes [4][6]. Group 3: Safety and Future Directions - Despite their benefits, GLP-1 receptor agonists are associated with potential adverse effects, including gastrointestinal issues and risks of serious complications like kidney damage [8][9]. - Ongoing research aims to optimize dosing regimens and identify the best patient populations for these therapies, balancing efficacy and safety [9][10]. - The exploration of GLP-1's role in metabolic regulation continues, with potential implications for future targeted therapies in metabolic diseases [10][12].

Core Viewpoint - The article discusses the approval and potential impact of the dual receptor agonist Mazdutide (信尔美®), developed by Innovent Biologics and Eli Lilly, for weight management in overweight and obese adults in China. This drug is the first of its kind globally, targeting both GLP-1 and GCGR receptors to enhance weight loss and metabolic health [2][4][12]. Group 1: Drug Approval and Mechanism - Mazdutide has received approval from the National Medical Products Administration in China for long-term weight control in adults with obesity or overweight [2]. - Unlike traditional single-target GLP-1 receptor agonists, Mazdutide activates both GLP-1 and glucagon (GCG) receptors, combining appetite suppression and energy expenditure to improve metabolic health [4][9]. - The drug's dual mechanism allows it to effectively reduce body weight while also improving liver lipid metabolism, showcasing its potential in managing metabolic diseases [4][18]. Group 2: Clinical Efficacy and Safety - Multiple clinical studies have confirmed the efficacy and safety of Mazdutide, with significant weight loss and improvement in metabolic markers observed [5][21]. - The GLORY-1 Phase III clinical trial, led by a Chinese research team, demonstrated that Mazdutide significantly reduced weight and improved various metabolic indicators in overweight or obese populations [6][12]. - At 48 weeks, participants receiving Mazdutide showed an average weight reduction of -12.0% and -14.8% for the 4mg and 6mg doses, respectively, compared to a -0.5% reduction in the placebo group [20]. Group 3: Impact on Liver Health - Mazdutide has shown promising results in reducing liver fat content, which is crucial for addressing metabolic dysfunction-related fatty liver disease (MASH) [21][22]. - In participants with baseline liver fat content ≥10%, the drug resulted in a reduction of liver fat by -65.85% and -80.24% for the 4mg and 6mg doses, respectively, compared to -5.27% in the placebo group [22]. - The drug's ability to lower liver fat and improve metabolic health positions it as a potential treatment for MASH, which currently lacks effective therapies [21][22]. Group 4: Broader Implications and Future Research - The introduction of Mazdutide is expected to reshape the clinical treatment landscape for obesity and metabolic diseases in China, aligning with national health initiatives aimed at managing overweight and obesity [17][25]. - The drug's innovative delivery system enhances user convenience and safety, addressing common concerns associated with injectable medications [25]. - Ongoing and planned clinical studies will further explore Mazdutide's efficacy in various populations, including adolescents and patients with heart failure [29].