The Effect of SGLT2-inhibitor Dapagliflozin on the Fatty Acid Metabolism of the Kidneys and the Renal Sinus Fat : a Randomized, Placebo-controlled Study

Abstract

Dapagliflozin is an SGLT2-inhibitor that is used in the treatment of type 2 diabetes. This class of drugs have renal and cardiometabolic benefits, including reducing visceral fat, lowering blood pressure and modulating whole body metabolism. The aim of our study was to see how dapagliflozin affects fatty acid metabolism of the kidneys, and see if dapagliflozin reduces renal sinus fat, which has been hypothesized to be the mechanism through which SGLT2-inhibitors lower blood pressure.

Our data has been collected from two different randomized, placebo-controlled studies: DERISC and DAPAKID. Participants were given either dapagliflozin 10 mg or placebo. Participants underwent imaging at the beginning and end of the experiment. Renal sinus fat was measured from MRI-images using Carimas-software. Renal fatty acid uptake was measured with FTHA-radiotracer from PET/CT-imaging.

At the end of treatment, renal sinus fat had decreased in the left kidney in the dapagliflozin treatment group. No change was seen between groups on the right side. A negative correlation was seen between HbA1c and change in renal sinus fat in the left kidney. We did not see a significant effect on renal fatty acid uptake.

In conclusion, our results showed that a short intervention with dapagliflozin affects the volume of renal sinus fat modestly but is unlikely the reason for the renal and cardiometabolic benefits associated with SGLT2-inhibitors. In contrast to previous research on other tissues, dapagliflozin did not alter renal fatty acid uptake significantly.