Sodium-Glucose Cotransporter 2 Inhibitors Improve Pancreatic ß-Cell Function by the Relief of ß-Cell Distress in Japanese Type 2 Diabetes

Abstract

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapies have demonstrated efficacy and safety in the treatment of type 2 diabetes (T2D). Recent studies suggested the potential roles of SGLT2i in the restoration of pancreatic β-cell function. SGLT2i is a new class of antidiabetic agent, independent from insulin action, however, its mechanism are not enough elucidated. We investigated the effects of SGLT2i on pancreatic β-cell function in T2D patients. This open-label, single-arm trial was conducted in our single medical hospital. A total of 30 patients (mean age 57.9±9.0 years, hemoglobin A1c 8.35±1.09%, BMI 29.2±4.5 kg/m2, diabetes duration 9.6±7.0 years) received some kinds of SGLT2i, canagliflozin, dapagliflozin or empagliflozin. Any change in the medication of oral hypoglycemic agents was not prohibited during the period of this trial. After 3 months of treatment, changes in hemoglobin A1c,body weight, fat mass, proinsulin-to-C-peptide ratio (ProINS/CPR, as an indicator of distressed pancreatic β-cell) and secretory units of islets in transplantation index (SUIT, as a marker of pancreatic β-cell function) were evaluated. Mean hemoglobin A1c decreased from 8.35 to 7.39% (p<0.01), and body weight decreased from 81.3 to 79.3 kg (p<0.01), significantly. ProINS/CPR ratio decreased from 0.037 to 0.031 (p=0.022), whereas SUIT index restored from 35.3 to 47.8 (p<0.01). We found a linear negative relationship between δProINS/CPR ratio and δSUIT index (r(2)=0.338, p<0.01). Multivariate analysis revealed that only baseline ProINS/CPR ratio was independently associated with SUIT index restoration (β=0.673, p<0.01), whereas older age, longer diabetic duration, body weight, fat mass, hemoglobin A1c were not associated. These results suggest that SGLT2i improves pancreatic β-cell function by the relief of β-cell distress, independent of the efficacy of glycemic control and body weight loss effect. Disclosure T. Yamamoto: None.