Effects of SGLT-2 inhibitors on thyroid-stimulating hormone and systemic immune-inflammation index in type 2 diabetes: a retrospective study

This retrospective study examined whether long-term SGLT-2i use is associated with differences in thyroid-stimulating hormone (TSH) and the systemic immune-inflammation index (SII) in patients with type 2 diabetes mellitus (T2DM) without known thyroid disease. The neutrophil-to-lymphocyte ratio (NLR), renal function (eGFR), diabetes duration, and metformin use were also evaluated as potential covariates. This was a single-center, retrospective observational study. Adults with T2DM who had used empagliflozin or dapagliflozin for at least six months were compared with an age- and sex-matched control group of patients with T2DM not using SGLT-2i, drawn from the same outpatient clinics. Key exclusion criteria included known thyroid disease, known positivity for thyroid autoantibodies, active inflammatory or autoimmune processes, advanced organ failure, and immunomodulatory treatment. TSH, SII, and NLR were measured. Statistical analyses included intergroup comparisons, correlation, multivariate linear regression, post-hoc power calculation, and multicollinearity diagnostics (variance inflation factor, VIF). The study included 330 patients across the empagliflozin ( n = 139), dapagliflozin ( n = 85), and control ( n = 106) groups. Median TSH (1.6, 1.8, and 1.9 µIU/mL; p = 0.338) and SII (481, 531, and 468.5; p = 0.509) did not differ significantly between groups. SII and NLR were significantly correlated ( r = 0.467, p < 0.001). In multivariate regression, female sex (B = 0.161, p = 0.015) and eGFR (B=–0.0043, p = 0.037) were independent predictors of log-transformed TSH; SGLT-2i use, SII, NLR, age, metformin use, and diabetes duration were not. The study had 80% power to detect a Cohen’s f of 0.17 or greater; observed effect sizes were substantially below this threshold (f = 0.02 for TSH, f ≈ 0.00 for SII). Long-term SGLT-2i use was not associated with significant changes in TSH or SII in patients with T2DM without known thyroid disease, and the achieved effect sizes suggest that any true effect, if present, is likely small. Renal function emerged as an independent correlate of TSH, suggesting that the relationship between the hypothalamic-pituitary-thyroid axis and renal physiology merits further attention in this population, independent of SGLT-2i exposure. Prospective, multicenter studies incorporating free thyroxine and triiodothyronine measurements are warranted to further clarify these relationships. This study is retrospective and does not involve a clinical trial registration.