Dapagliflozin and semaglutide yield greatest absolute BMI reduction in Obesity III patients, proportional response uniform.

Saudi Arabia faces a high prevalence of obesity and diabetes mellitus, with cardiovascular disease being a leading cause of mortality. Sodium-glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin and glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide are key therapeutic agents for these conditions, primarily targeting weight reduction and glycemic control. However, it remains unclear how the BMI response to these medications, alone or in combination, varies across different WHO BMI classes, particularly in real-world settings. This study addresses that gap, providing insights into class-specific efficacy.

Researchers conducted a retrospective observational cohort study involving 328 patients initiated on dapagliflozin 10 mg once daily with or without once-weekly semaglutide at a Saudi Arabian hospital. Patients were followed for 90-365 days. The primary outcome measured was absolute ΔBMI, while secondary outcomes included proportional BMI change and the proportion achieving ≥5% reduction in BMI. The cohort was stratified into WHO BMI classes: Normal (n = 23), Overweight (n = 57), Obesity I (n = 87), Obesity II (n = 89), and Obesity III (n = 72). Multivariable sensitivity analysis adjusted for age, baseline BMI, treatment group, and sex to isolate the effects.

Absolute ΔBMI differed significantly across the WHO BMI classes (Kruskal-Wallis, p = 0.005). The most substantial absolute BMI reduction was observed in the Obesity III group, with a mean change of -1.05 kg/m², significantly greater than the -0.09 kg/m² seen in the Normal weight group (Bonferroni p_adj = 0.017). In contrast, the proportional BMI change was found to be uniform across all classes (p = 0.182), suggesting that the greater absolute reduction in higher BMI classes primarily reflects their higher baseline BMI rather than a class-specific pharmacological advantage. Baseline BMI emerged as the dominant predictor of BMI reduction (β = -0.38, p < 0.001), although Obesity III status retained an independent association with greater absolute reduction (β = -0.59, p = 0.021).