Comparative change in HbA1c and weight outcomes between obese and non-obese adults with type 2 diabetes mellitus treated with SGLT-2 inhibitors or GLP-1 receptor agonists.

Background: Obesity and type 2 diabetes mellitus (T2DM) are closely linked through shared pathophysiological mechanisms affecting glucose metabolism and insulin resistance. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely recommended for patients with T2DM who are overweight or obese because of their favorable effects. However, whether baseline obesity influences the glycemic response to these agents in real-world clinical practice remains unclear. Methods: This multicenter retrospective study included adults with T2DM initiated on either SGLT2i or GLP-1RA at three healthcare centers in Riyadh, Saudi Arabia. Patients were stratified into obese (BMI ≥30 kg/m²) and non-obese (BMI <30 kg/m²). Changes in HbA1c, body weight, and BMI were evaluated at 3, 6, 9, and 12 months. Between-group comparisons were performed using independent t-tests, followed by mixed-effects models for repeated measures (MMRM) to adjust for potential confounders. Secondary outcomes included the proportions of patients achieving ≥5% weight loss, HbA1c <7.0% (among those uncontrolled at baseline), and HbA1c reductions of ≥0.5% and ≥1.0%. Results: A total of 1,016 patients were included, of whom 73.4% were obese. Obese patients were associated with greater reductions in absolute body weight and BMI at 3, 6, 9, and 12 months than non-obese patients, although their higher baseline body weight may have contributed to these differences. Responder analysis showed that obesity was associated with a higher likelihood of achieving ≥5% weight loss at months 3 (21.9% vs. 12.0%, p=0.0016) and 6 (27.2% vs. 15.5%, p=0.0086). In the adjusted MMRM, obesity was associated with greater least-squares mean reductions in weight and BMI (p<0.05), whereas HbA1c reductions and responder rates (HbA1c <7.0%, ≥0.5%, and ≥1.0% reductions) were statistically comparable between groups. Conclusion: These findings suggest that baseline obesity was associated with greater reductions in anthropometric measures following SGLT2i or GLP-1RA therapy after multivariable adjustment, whereas improvements in glycemic control were similar between obese and non-obese patients. As these findings are hypothesis-generating, prospective studies are needed to determine whether baseline BMI modifies treatment response.