#5699 IS GFR DECLINE INDUCED BY SGLT-2 INHIBITOR OF CLINICAL IMPORTANCE?

Abstract

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcome and with nephroprotection independent of diabetes status. However, the use of SGLT2i often cause an initial decline in estimated glomerular filtration rate (eGFR). This study addresses the question whether there is a relationship between vascular improvement and GFR dipping. Method We measured GFR (mGFR) and calculated GFR (eGFR) in 65 patients with T2D at baseline and after 12 weeks of treatment with either a combination of Empagliflozin (E) + Linagliptin (L) (n = 34) or Metformin (M) + Insulin (I) (n = 31). mGFR was measured using the gold standard clearance technique by infusion of inulin. In addition, pulse wave velocity (PWV) was obtained at office and under ambulatory conditions. We splitted the study cohort according to the median change of mGFR after 12 weeks and compared the baseline characteristics. Results mGFR and eGFR decreased significantly with E+L and with M+I (Ott C et. al. Cardiovasc Diabetol. 2021). However, no correlation was noticed between the change of mGFR and change of eGFR for either treatment cohorts (E+L: p = 0.404; M+I: p = 0.460). We found a significant decrease in office PWV in the E+L group only (8.2±1.6 to 7.8±1.5, p = 0.028) without any change in 24-h PWV. The change of office PWV correlated with the change of mGFR (p = 0.009) in E+L group only and remained significant after adjustment for the change of office systolic BP (p = 0.018). In addition, we observed a correlation between the change of high sensitive C reactive protein (hsCRP) and change in mGFR (p = 0.031). We identified patients with higher albumin excretion (p = 0.044), higher fasting plasma glucose (p = 0.014) and high hsCRP (p = 0.057) to have a greater decline in mGFR with E+L. Conclusion First, eGFR may not be an appropriate parameter to assess the true change in renal function after receiving E+L in a single patient. Second, after E+L medication a high decrease in mGFR goes in parallel with vascular improvement and less inflammation thereby reflecting the pleiotropic pharmacologic effects of SGLT 2 inhibitors.