In addition to their known hypoglycemic effects, sodium-glucose cotransporter-2 (SGLT2) inhibitors have also been reported to show cardio-renal protective effects in recent studies. Pharmacological treatment of diabetes mellitus is based on combinations of drugs with different actions to control blood glucose and reduce the three major complications of the disease. However, the renoprotective effects of many of these drug combinations remain unknown. In this study, we investigated the renoprotective effects of the combination of a dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and an SGLT2 inhibitor canagliflozin.

The target period is from April 2017 to March 2022.Patients were those who were prescribed vildagliptin by the department of nephrology at our hospital from April 2017 to March 2022, and were divided into a vildagliptin-only group and a canagliflozin-combined groups. Estimated glomerular filtration rate (We set eGFR) and urine albumin-creatinine ratio (UACR) were used as primary endpoints, and investigated renoprotective factors were investigated. The results showed that the combination of canagliflozin reduced the rate of urine albumin-to-creatinine ratio (UACR) suppression by 0.01 g/gCr per year (P = 0.97) and the rate of estimated glomerular filtration rate (eGFR) decline by 0.19 mL/min/1.73m² per year in comparison with vildagliptin alone (P < 0.05), indicating a renoprotective effect. As a result of Mmultiple regression analysis using eGFR as the objective variable and age, HbA1c , and UACR as explanatory variables showed, a significant difference was found only in UACR (P < 0.05). Moreover, this effect was independent of the concomitant use of renin-angiotensin system inhibitors.

The results of this study suggested that the combined use of vildagliptin and canagliflozin may have a renoprotective effect. It was clarified that this effect was due to urinary protein reduction. Considering the number of combinations of DPP4 inhibitors and SGLT2 inhibitors used in clinical practice, future studies should aim to evaluate the renoprotective potential of other combinations and verify their efficacy.