Longitudinal Changes in Insulin Resistance Indices During SGLT2 Inhibitor Therapy in Type 2 Diabetes: A Prospective Observational Cohort Study

Background/Objectives: Glucose-lowering treatment can change insulin resistance indices without demonstrating improved insulin sensitivity. We described these changes during sodium–glucose cotransporter-2 (SGLT2) inhibitor therapy in routine care. Methods: In this prospective, uncontrolled observational cohort, 54 adults with type 2 diabetes were assessed at baseline, 3 and 6 months. Background medication was abstracted from hospital and prescription records. Exploratory baseline-to-6-month comparisons used Wilcoxon signed-rank tests with Benjamini–Hochberg adjustment across 15 analysed outcomes. Results: Median HOMA-IR decreased from 8.38 (IQR 3.47–13.26) to 3.14 (2.19–4.39), a 62.6% reduction in group medians (rank-biserial r = −0.79; adjusted p < 0.001); in the 41 participants without documented insulin use, the reduction was 50.9% (r = −0.76). Median triglyceride–glucose (TyG) index decreased from 9.45 to 9.04 (−4.3%; r = −0.63; adjusted p < 0.001). Change in HOMA-IR was not significantly correlated with change in HbA1c (ρ = −0.15; p = 0.27). Conclusions: Both indices decreased during follow-up, including in participants without documented insulin use, but these observations cannot establish a treatment effect or improved insulin sensitivity. TyG requires no insulin measurement but remains sensitive to glucose- and triglyceride-lowering therapies, including SGLT2 inhibitors. Controlled studies with direct measures of insulin sensitivity are needed.