Relation between HOMA-IR and insulin sensitivity index determined by hyperinsulinemic-euglycemic clamp analysis during treatment with a sodium-glucose cotransporter 2 inhibitor

Abstract

We had aimed to determine whether homeostasis model assessment–insulin resistance (HOMA-IR) reflects insulin resistance-sensitivity during treatment with a sodium-glucose cotransporter 2 inhibitor (SGLT2i). Hyperinsulinemic-euglycemic clamp analysis was performed in 22 patients with type 2 diabetic patients taking dapagliflozin (5 mg/day before or after breakfast). Propensity score matching of these individuals (SGLT2i group) for age, sex, body mass index, and clamp-derived tissue glucose uptake rate with 44 type 2 diabetic patients who had undergone clamp analysis without SGLT2i treatment (control group) identified 17 paired subjects in each group for further analysis of the relation between HOMA-IR and a clamp-derived insulin sensitivity index (ISI). Natural log–transformed HOMA-IR was negatively correlated with ISI in both SGLT2i (r = –0.527, p = 0.030) and control (r = –0.534, p = 0.027) groups. The simple regression lines for log-transformed HOMA-IR and ISI in the two groups showed similar slopes but differed in their intercepts. Multivariate analysis revealed that HOMA-IR for patients with the same ISI in the two groups was related by the formula: HOMA-IR_control = HOMA-IR_SGLT2i × 2.45. In conclusion, HOMA-IR was well correlated with ISI during SGLT2i treatment, but values corresponding to the same ISI were lower in the SGLT2i group than in the control group.