Core Insights - The article discusses a systematic review and meta-analysis published by researchers from Xiangya Second Hospital, focusing on weight loss medications approved by the FDA and EMA [2][4]. Research Background - Overweight and obesity pose significant health challenges for individuals and society. The study aims to promote personalized treatment for obesity by summarizing recent research on weight loss medications, emphasizing their effects on weight loss, cardiovascular metabolic health, psychological outcomes, and adverse events [4]. Research Methodology - The systematic review and meta-analysis included randomized controlled trials assessing weight loss medications approved by the FDA or EMA for treating overweight or obesity, with a search conducted until June 8, 2024. Key outcomes included weight change, cardiovascular metabolic indicators, psychological outcomes, and adverse events [5][6]. Research Results - A total of 154 randomized controlled trials involving 112,515 participants were included. Tirzepatide showed the best weight loss effect, followed by Semaglutide. Tirzepatide exhibited the strongest antihypertensive effects and best reductions in triglycerides, fasting blood glucose, insulin, and HbA1c levels. Semaglutide and Liraglutide reduced the risk of major adverse cardiovascular events (MACE). However, some medications, such as Naltrexone/Bupropion, increased blood pressure risk, and Phentermine/Topiramate had higher risks of psychological side effects [8]. Tirzepatide Efficacy - The SURMOUNT-1 study demonstrated that Tirzepatide significantly reduced weight in patients with obesity or overweight and prediabetes over 176 weeks, with average weight reductions of 15.4% (5mg), 19.9% (10mg), and 22.9% (15mg) compared to a 2.1% reduction in the placebo group. Tirzepatide also reduced the risk of diabetes progression by 88% compared to placebo [10][12][13]. - In the SURMOUNT-3 trial, patients experienced up to a 26.6% weight loss after 12 weeks of lifestyle intervention and 72 weeks of Tirzepatide treatment. The SURMOUNT-4 trial showed an average weight loss of 26.0% over 88 weeks [14]. - The SURMOUNT-5 trial indicated that participants receiving Tirzepatide lost an average of 50.3 pounds (approximately 22.8 kg), significantly outperforming the active control group [15]. Semaglutide Efficacy - The STEP series of studies revealed that Semaglutide achieved an average weight loss of 15% in obese patients, demonstrating good safety. The STEP 1 study showed a 14.9% weight reduction, with over one-third of participants losing more than 20% of their weight [16][18]. - In the STEP 2 study, Semaglutide led to a 10.6% weight loss in patients with type 2 diabetes, with improvements in cardiovascular risk factors and quality of life [20]. - The STEP 3 study indicated that Semaglutide combined with behavioral therapy resulted in a 16% weight loss, while the STEP 4 study showed a sustained weight loss of 18.2% over time [21]. - Overall, the STEP trials demonstrated that Semaglutide could significantly lower body mass index, blood pressure, fasting insulin levels, and waist circumference, with FDA approval granted for its use in managing obesity [22].