Introduction: Semaglutide, a GLP-1 receptor agonist approved for obesity treatment, has shown significant weight loss in trials. However, real-world effectiveness may vary due to patient-specific factors. This study evaluated weight loss in routine clinical settings and how baseline metabolic and comorbid conditions influence response.

Methods: Retrospective observational study in 281 adults with obesity treated with semaglutide over ∼6 months. Baseline demographics, comorbidities, and body composition data were collected. Paired t-tests assessed weight changes, and ANOVA evaluated the influence of baseline variables.

Results: Mean age was 52.85 ± 13.21 years; 76.2% were women. Common comorbidities: dyslipidemia (46.2%), hypertension (40.4%), hepatic steatosis (24.4%), and sleep apnea (17.1%). Type 1 diabetes affected 3.6%, and 9.1% had prior bariatric surgery. Initial weight and BMI were 93.30 ± 21.15 kg and 34.87 ± 6.03 kg/m², decreasing to 83.05 ± 27.98 kg and 26.83 ± 14.06 kg/m². Mean weight loss was 10.20 ± 24.89 kg (p < 0.001). ANOVA showed that type 1 diabetes, chronic kidney disease, prior myocardial infarction, and higher FIB-4 scores were linked to less weight loss (all p < 0.001). Also associated with poorer outcomes were dyslipidemia (p = 0.001), hepatic steatosis (p = 0.019), sedentarism (p = 0.021), prior bariatric surgery (p = 0.028), and sleep apnea using CPAP (p < 0.001). Smoking influenced weight loss (p < 0.001), while age, hypertension, and heart failure did not show significance.

Conclusions: Semaglutide is effective in real-world use, leading to considerable weight loss. Yet, several comorbidities may attenuate the response, underlining the importance of personalized treatment strategies. Semaglutide achieves meaningful weight reduction in practice. Baseline characteristics can significantly affect outcomes, supporting the role of individualized approaches in obesity management.