Core Viewpoint - The STEP 5 trial demonstrates that semaglutide 2.4 mg is effective for long-term weight management in obese adults without type 2 diabetes, showing significant and sustained weight loss over a two-year period [2][3][4]. Group 1: Trial Overview - STEP 5 is a phase 3b randomized, double-blind, placebo-controlled trial involving 304 adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) [3][4]. - Participants were assigned to receive either weekly subcutaneous injections of 2.4 mg semaglutide or a placebo, alongside a low-calorie diet and increased physical activity, for 104 weeks [3][4]. - The primary endpoint was the percentage change in weight and the proportion of participants achieving a weight loss of ≥5% by week 104 [3]. Group 2: Weight Loss Results - The semaglutide group experienced a weight loss of -15.2%, compared to -2.6% in the placebo group [4]. - 77.1% of participants in the semaglutide group lost at least 5% of their body weight, while only 34.4% in the placebo group achieved this [4]. Group 3: Safety and Side Effects - Common adverse events associated with semaglutide included nausea, diarrhea, vomiting, constipation, and abdominal pain [6]. - The safety profile of semaglutide in STEP 5 was consistent with previous trials, with 5.9% of patients discontinuing treatment due to adverse events [6]. Group 4: Health Improvements - Significant improvements were observed in waist circumference (-14.4 cm in the semaglutide group vs. -5.2 cm in the placebo group) and systolic blood pressure (-5.7 mmHg vs. -1.6 mmHg) [7]. - Semaglutide also improved various metabolic health markers, including HbA1c, fasting blood glucose, and lipid profiles [7]. Group 5: STEP Trial Context - The STEP program is a comprehensive phase 3 clinical development plan for semaglutide, involving approximately 4,500 overweight or obese adults across multiple trials [8].