Core Viewpoint - The efficacy of semaglutide for weight management is consistently superior in non-diabetic patients compared to diabetic patients, with potential explanations discussed in the article [2][3]. Group 1: Efficacy in Non-Diabetic Patients - In non-diabetic patients, semaglutide leads to an average weight loss of 10.3% to 17.4%, while diabetic patients experience an average weight loss of 6.2% [3]. - The STEP series of clinical trials, which included approximately 25,000 overweight and obese participants, demonstrated that semaglutide significantly reduces weight, achieving an average weight loss of 17% (16.8 kg) regardless of the presence of type 2 diabetes [5]. - In the STEP trials, the proportion of participants achieving a weight loss of ≥ 5% with semaglutide was between 86.4% and 88.7% [8]. Group 2: Efficacy in Diabetic Patients - The STEP 2 trial, a double-blind, placebo-controlled study, evaluated semaglutide 2.4 mg against semaglutide 1.0 mg and placebo in overweight or obese adults with type 2 diabetes, showing an average weight loss difference of 6.2% compared to placebo [9]. - The proportion of participants in the STEP 2 trial achieving a weight loss of ≥ 5% with semaglutide was 68.8% [9]. Group 3: Explanations for Efficacy Differences - Previous studies have noted that diabetic patients find it more challenging to lose weight compared to non-diabetic patients, with several hypotheses proposed for this discrepancy [10]. - Factors such as concomitant medications that promote weight gain, fear of hypoglycemia leading to increased food intake, and reduced energy expenditure in diabetic patients may contribute to the observed differences in weight loss efficacy [12][13]. - The complex pathophysiology of obesity in diabetic patients, including longer duration of obesity and lower exercise adherence, may also enhance the effects of GLP-1 receptor agonists [13].