Background: Despite the recent evidence of SGLT2-inhibitors (SGLT2i) in renal function protection, the treatment of ACEI/ARB and pioglitazone may also be promising to diabetic kidney disease progression. This study aims to discuss the interplay between SGLT2i, ACEI/ARB and pioglitazone to changes of renal function in patients with type 2 diabetes (T2DM).

Materials and Methods: Patients with T2DM who initialized SGLT2i over six months and had at least two serum creatinine examinations were included in the present study. We categorized our participants into three groups according to their ACEI/ARB and pioglitazone status. GEE was used to analyze significant factors for subsequent EPI changes.

Results: A total of 253 patients with T2DM were included in the present study. Their SGLT2i treatment duration was 23.7±9.6 months and serum creatinine was followed 4.1± 1.6 times during the study period. After SGLT2i initiation, A1C reduced 0.5%, body weight decreased 2.2 kg, systolic blood pressure dropped 6 mmHg and LDL-C lowered 7 mg/dl; however, EPI showed a J-curve improvement as treatment duration increased (P=0.021). To disclose the interaction between ACEI/ARB and pioglitazone in these SGLT2i users, we categorized our participants into three groups, and the number of patients in the ACEI/ARB(-)/pioglitazone(-), ACEI/ARB(+)/or pioglitazone(+) and ACEI/ARB(+)/pioglitazone(+) group was 83, 133 and 37, respectively. In the consideration of the effect of age, gender, body weight, A1C, albuminuria status, treatment duration, systolic and diastolic blood pressure and LDL-C, we found SGLT2i users who simultaneously under ACEI/ARB and pioglitazone therapy had a significant renal function deterioration by 5.77 mL/min/1.73m2 (P=0.011) as compared with other two group.

Conclusions: Our study suggested that the encouraging renal effect brought by SGLT2i may be lessened in patients with T2DM who simultaneously under ACEI/ARB and pioglitazone treatment.


T. Lee: None.

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