Objective To investigate the effects of Semaglutide injection on glycolipid metabolism and adipokine levels in the treatment of type 2 diabetes mellitus （T2DM） patients with varying body mass index （BMI）. Methods A total of 143 patients with T2DM admitted to our hospital between May 2022 and May 2024 were enrolled in this study. Based on their BMI， the patients were categorized into three groups： the normal-weight group （31 cases， 18.5 kg/m² ≤ BMI < 24 kg/m²）， the super-recombinant group （49 cases， 24 kg/m² ≤ BMI < 28 kg/m²）， and the obese group （63 cases， 28 kg/m² ≤ BMI）. 28 kg/m² ≤ BMI）. All participants received standard guideline-based conventional treatment and were additionally administered semaglutide injections for a duration of 12 weeks. The study compared glucose metabolism， islet β-cell function， lipid metabolism， body composition， adipokine levels before treatment and at 12 weeks post-treatment， as well as safety profiles during the treatment period across the three groups. Results After 12 weeks of treatment， the levels of fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG）， glycated hemoglobin （HbA1c）， insulin resistance index （HOMA-IR）， serum triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） decreased in all three groups. Specifically， the reductions were more pronounced in the obesity group compared to the normal group and the super-reorganization group， and the super-reorganization group showed intermediate reductions between the obesity and normal groups （P < 0.05）. Conversely， fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， irisin， adipsin， and omentin-1 levels increased in all three groups after treatment， with the greatest increases observed in the obesity group， followed by the super-reorganization group， both of which were significantly higher than the normal group （P < 0.05）. Additionally， high-density lipoprotein cholesterol （HDL-C） levels increased in all three groups after 12 weeks of treatment （P < 0.05）. BaselineBMI and total body fat mass （WBFM） were significantly higher in the obesity group compared to the super-reorganization group， which in turn were higher than the normal group （P < 0.05）. After treatment， BMI and WBFM decreased in both the obesity and super-reorganization groups， but remained significantly higher than in the normal group （P < 0.05）. The incidence of adverse reactions during treatment was 12.90% （4/31）， 10.20% （5/49）， and 11.11% （7/63） in the normal， super-reorganization， and obesity groups， respectively， with no statistically significant differences among the groups （P > 0.05）. Conclusion Smiglutide injection can improve glucose and lipid metabolism， islet function， and adipokine levels in T2DM patients across different BMI categories， while also regulating body composition. It demonstrates a particularly strong improvement effect on glucose and lipid metabolism， islet function， and adipokine levels in overweight and obese T2DM patients. Additionally， smiglutide does not increase safety risks.