Comparison of Renal and Metabolic Effects of Empagliflozin and Dapagliflozin on Type 2 Diabetes-Induced Rats

Background: Diabetes mellitus is a disease that affects millions of people worldwide. Extensive clinical studies are ongoing on Empagliflozin and Dapagliflozin, in patients with heart failure and chronic renal failure. The aim of this study is to investigate the equivalence and superiority of different SGLT2 inhibitors by comparing the metabolic and renal effects. Methods: 44 Sprague-Dawley rats were divided into four groups, which had unrestricted access to food and water (ad libitum). Following a three-week high-fat diet, streptozotocin was administered, and groups were randomly divided based on mean glucose levels. Treatment was applied for one month. Serum and urine samples were collected before and after 1 month of the treatment. Urine samples were analysed with NMR and confirmed with Mass Spectrometry. Kidneys were collected at the end of the experiment for histological analysis. Results: The Empa-treated group had considerably decreased blood glucose levels as compared to the Dapa group (p<0.001). While treatment groups did not exhibit a meaningful increase in plasma insulin levels, the placebo group did (p=0.027). The placebo group had a significant increase in BUN levels (p=0.006), but the treatment groups did not exhibit this change. Both Empa and Dapa-treated groups ameliorated interstitial inflammation, mesangial expansion, and basal membrane thickening equally well. Conclusions: In conclusion, different molecules from the SGLT2-inhibitors are not equally effective on various parameters. In terms of blood and urine parameters, Empagliflozin outperformed Dapagliflozin, while both medicines showed equal improvement in terms of kidney histology. Our research demonstrates that SGLT2 inhibitors' renoprotective effects extend beyond their glucose-lowering properties. Funding: Commercial Support - The Scientific and Technological Research Council of Turkey (TUBITAK)Table 1.: Urinary ParametersFig.1.1: Placebo Group Mesengial Expansion and Basal Membrane Thickening with PAS StainFig.1.2: Empa Group with PAS Stain