BMI response to dapagliflozin with or without semaglutide across obesity classes: a real-world observational study conducted in Saudi Arabia

BACKGROUND: Obesity is highly prevalent in Saudi Arabia and is a primary therapeutic target for SGLT2 inhibitors and GLP-1 receptor agonists. Whether BMI response to dapagliflozin ± semaglutide varies across WHO BMI classes remains incompletely characterized. OBJECTIVE: To examine absolute and proportional BMI changes across WHO BMI classes in a real-world Saudi cohort, using normal weight as the reference group. METHODS: A retrospective observational cohort of 328 patients initiated on dapagliflozin ± once-weekly semaglutide at King Abdulaziz Hospital, MNGHA, Al-Ahsa (follow-up 90-365 days). The primary outcome was absolute ΔBMI; secondary outcomes included proportional BMI change and ≥5% reduction. Multivariable sensitivity analysis adjusted for age, baseline BMI, treatment group, and sex. Dapagliflozin 10 mg once daily was the only available formulation; individual semaglutide dose data were unavailable. RESULTS: Normal (n = 23), overweight (n = 57), obesity I (n = 87), obesity II (n = 89), obesity III (n = 72). Absolute ΔBMI differed significantly across classes (Kruskal-Wallis, p = 0.005), with the greatest reduction in Obesity III (-1.05 vs. -0.09 kg/m² in Normal; Bonferroni p_adj = 0.017). Proportional change was uniform (p = 0.182), indicating the absolute gradient reflects higher baseline BMI. Baseline BMI was the dominant predictor (β = -0.38, p < 0.001); Obesity III retained independent association (β = -0.59, p = 0.021). CONCLUSIONS: Absolute BMI reduction was greatest in Obesity III, but proportional response was uniform across classes, reflecting baseline BMI rather than class-specific pharmacological advantage. Semaglutide add-on showed a directional trend toward greater benefit in obesity I. These exploratory findings support obesity-class-informed monitoring and provide a basis for prospective studies.