Ponirakis G, Abdul-Ghani MA, Jayyousi A, et al. - In this exploratory sub-study of an open-label, randomized controlled trial, experts aspired to explore whether insulin resistance (IR) in patients with type 2 diabetes (T2D) undergoing intensive glycemic control determines the extent of improvement in neuropathy. The sample consisted of patients with poorly controlled T2D treated with exenatide and pioglitazone or insulin to achieve an HbA1c < 7.0% (< 53 mmol/mol). Using corneal confocal microscopy, baseline IR was defined using HOMA-IR and change in neuropathy was evaluated. Participants in the study were 38 T2D patients aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR. Treatment resulted in a significant decrease in HbA1c, diastolic blood pressure, total cholesterol, and LDL, as well as an increase in body weight. Individuals with HOMA-IR < 1.9 had significantly higher corneal nerve fiber density, length, and branch density, whereas those with HOMA-IR ≥ 1.9 had no change. Nerve regeneration may be limited in T2D and IR patients receiving pioglitazone plus exenatide or insulin to improve glycemic control.