A Prospective Study on the Metabolic and Hormonal Outcomes of SGLT2 Inhibitor Combination Therapy With and Without Metformin in Newly Diagnosed Type 2 Diabetes Mellitus

Background/Objectives: The rising global burden of type 2 diabetes mellitus (T2DM) demands multifaceted and more effective treatment strategies beyond monotherapy to achieve optimal metabolic control. The study aimed to evaluate the integrated effects of SGLT2 inhibitors and metformin in newly diagnosed T2DM patients on biochemical parameters, clinical outcomes and hormonal changes. Methods: This prospective longitudinal study was conducted at the Department of Biochemistry, Baqai Medical University, in collaboration with the Baqai Institute of Diabetology and Endocrinology. A total of 120 newly diagnosed T2DM patients were enrolled and stratified into three groups (n = 40): Group 1 (SGLT2 inhibitors only), Group 2 (SGLT2 inhibitors + metformin), and Group 3 (metformin only). Patients were followed for six months with data collection at baseline, at 3 months and 6 months. Anthropometric indices (weight, BMI, waist and hip circumferences, WHR), biochemical markers (FBS, HbA1c, lipid profile, uric acid, serum creatinine, HOMA-IR), and hormonal levels (insulin, glucagon) were assessed at baseline, first follow-up, and second follow-up. ANOVA, post hoc, Bonferroni and Tukey’s tests were applied; p-value < 0.05 was considered significant. Results: The findings indicate that Group 2 showed the greatest improvement in anthropometric parameters, particularly waist and hip circumferences (p < 0.01). Group 3 demonstrated the most significant improvement in glycemic indices and lipid profile (p < 0.01). HOMA-IR significantly decreased in Group 3 from baseline to the first follow-up (p < 0.01). While insulin levels remain insignificantly different among all groups. Glucagon levels declined significantly from baseline to the second follow-up in all groups, with a more pronounced decrease in Group 3 (p < 0.01). Serum creatinine and uric acid levels showed significant reductions from baseline to the second follow-up in Group 1 and Group 2 (p < 0.05). However, given the observational design, these associations should not be interpreted as causal evidence of renoprotection. Conclusions: Within the limitations of this observational study, early differences among treatment regimens were observed, though metabolic outcomes became statistically comparable across groups by six months. These hypothesis-generating findings suggest potential benefits of early combination therapy that require confirmation in randomized controlled trials. Given the substantial within-group variability and non-randomized design, no definitive conclusions about therapeutic associations can be drawn from these data.