Frontiers in endocrinology · 2026
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.
Сравнительное исследованиеСтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Almohammed Omar A, Alshaya Omar A, Alduhayshi Lama A, Alshaibani Sara T, Alhamed Meshal S, Alzeer Mohammed A, Alabdullah Othman M, Ibn Saqyan Mohamed F, Al Yami Majed S, Bin Sheraim Nader, Almohareb Sumaya N, Alfayez Osamah M, Korayem Ghazwa B
Аннотация
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.
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.