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Abstract: TH-PO910

Empagliflozin as an Add-On to Linagliptin Ameliorates Renal Interstitial Fibrosis in Spontaneously Diabetic Torii Fatty Rats

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Kodama, Goh, Kurume University School of Medicine, Kurume, Japan
  • Nakayama, Yosuke, Kurume University, Kurume, Japan
  • Ito, Sakuya, Kurume University School of Medicine, Kurume, Japan
  • Yokota, Yunosuke, Kurume University School of Medicine, Kurume, Japan
  • Kaida, Yusuke, Kurume University School of Medicine, Kurume, Japan
  • Fukami, Kei, Kurume University School of Medicine, Kurume, Japan

Group or Team Name

  • Division of Nephrology, Department of Medicine, Kurume University School of Medicine
Background

Recent clinical trials have shown that SGLT2 inhibitor significantly attenuates the rapid decline in eGFR and enhances blood pressure control. Further, DPP4-inhibitor has become the first-line therapy of blood glucose control in patients with diabetic kidney disease (DKD). However, whether dual therapy could prevent the development and progression of DKD are yet to be elucidated. Therefore, we investigated the effects of empagliflozin as an add-on to linagliptin or vice versa on diabetes-induced renal injury in SDT fatty rats, a type 2 diabetic model of DKD.

Methods

Eight-week-old SDT fatty rats were divided into 5 groups, 1) SDT fatty rats untreated (SDT), 2) SDT fatty rats given 30 mg/kg of empagliflozin for 12 weeks (EMPA), 3) SDT fatty rats given 3 mg/kg of linagliptin for 12 weeks (LINA), 4) SDT fatty rats given empagliflozin for 6 weeks in addition with linagliptin for 6 weeks (EMPA–EMPA+LINA), and 5) SDT fatty rats given linagliptin for 6 weeks in addition with empagliflozin for 6 weeks (LINA–LINA+EMPA). All experimental groups were given water supplemented with 0.5% salt. All animals (20 weeks of age) were euthanized and parameters such as urine and blood chemistry, blood pressure (BP), renal pathology, and GFR were measured.

Results

At 14 weeks of age, SDT exhibited hypertension, which was not ameliorated in EMPA and LINA groups. However, at 20 weeks of age, BP decreased in all treated groups. Treatment with empagliflozin showed glycosuria and increased urinary sodium excretion. SDT showed albuminuria and glomerulosclerosis, which were not ameliorated in all the treated groups. Compared with SD, GFR was significantly higher in SDT, suggesting hyperfiltration, and it further increased in LINA. SDT manifested dramatically increased urinary L-type fatty acid binding protein levels, which were attenuated in LINA–LINA+EMPA (p=0.069 vs SDT). Besides, renal interstitial fibrosis was ameliorated in EMPA, EMPA–EMPA+LINA, and further reduced in LINA–LINA+EMPA, as evidenced by the Masson trichrome staining. Diabetes-associated interstitial TGF-b expression was inhibited only in LINA–LINA+EMPA (p<0.05 vs SDT).

Conclusion

Empagliflozin as an add-on to linagliptin might be a better therapy for diabetes-induced renal fibrosis than linagliptin as an add-on to empagliflozin and each drug.