Effect of SGLT2 Inhibitors and Metformin on Inflammatory and Prognostic Biomarkers in Type 2 Diabetes Patients

Objective: To assess the combined effect of Sodium-Glucose Transporter 2 Inhibitors (SGLT2i) and metformin treatment on inflammatory and prognostic biomarkers in patients with T2DM. Methods: Using the search terms “Sodium-Glucose Transporter 2 Inhibitors,” “Diabetes Mellitus, Type 2,” and “randomized controlled trial,” we screened the literature on PubMed, Cochrane Library, Embase, and Web of Science according to the inclusion and exclusion criteria. The studies selected were grouped to determine the combined effect of SGLT2i and metformin on inflammatory markers in patients with T2DM. Results were expressed using continuous variables, combined into weighted mean differences (WMD) and 95% confidence intervals (CI). The study was registered under the PROSPERO number CRD42022296480. Results: Meta-analysis showed that, compared with the control and metformin treatment groups, the SGLT2i coupled with metformin group was more effective in reducing C-reactive protein (CRP) (WMD, −0.185, 95% CI, −0.330 to −0.040, P < 0.05), tumor necrosis factor (TNF-α) (WMD, −0.628, 95% CI, −1.046 to −0.210, P < 0.05), uric acid (WMD, −0.653, 95% CI, −0.734 to −0.572, P < 0.05), leptin (WMD, −3.663, 95% CI, −4.812 to −2.515, P < 0.05), glycated hemoglobin (HbA1c) (WMD = −0.172, 95% CI, −0.255 to −0.089, P < 0.05), and estimated glomerular filtration rate (eGFR)(WMD = 0.978, 95% CI (0.027, 1.928), P = 0.044). In parallel, we performed a Trial Sequential Analysis (TSA) of and the results showed reliable conclusions. Conclusion: SGLT2i combined with metformin reduced inflammation levels and significantly improved glycemic control and prognosis in patients with T2DM.