Effects of sodium-glucose cotransporter 2 inhibitor, tofogliflozin, on the indices of renal tubular function in patients with type 2 diabetes

Kiyohide Nunoi; Yuichi Sato; Kohei Kaku; Akihiro Yoshida; Hideki Suganami

doi:10.1002/edm2.15

Effects of sodium-glucose cotransporter 2 inhibitor, tofogliflozin, on the indices of renal tubular function in patients with type 2 diabetes

Endocrinol Diabetes Metab. 2018 Mar 26;1(2):e00015. doi: 10.1002/edm2.15. eCollection 2018 Apr.

Authors

Kiyohide Nunoi¹, Yuichi Sato¹, Kohei Kaku², Akihiro Yoshida³, Hideki Suganami⁴

Affiliations

¹ Division of Endocrinology and Metabolism St. Mary's Hospital Fukuoka Japan.
² Department of Internal Medicine Kawasaki Medical School Okayama Japan.
³ Medical Information and Product Advancement Department Kowa Pharmaceutical Company, Ltd. Tokyo Japan.
⁴ Clinical Data Science Department Kowa Company, Ltd. Tokyo Japan.

PMID: 30815551
PMCID: PMC6354802
DOI: 10.1002/edm2.15

Abstract

Aims: Little is known of the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the renal tubules. We investigated the effect of the SGLT2 inhibitor, tofogliflozin (TOFO) on renal tubular indices, according to the degree of albuminuria, in type 2 diabetes mellitus (T2DM) patients with preserved renal function.

Materials and methods: A total of 988 patients, receiving TOFO, were enroled and divided into 3 groups, based on the urine albumin-to-creatinine ratio (UACR). The tubular indices (urinary N-acetyl-beta-d-glucosaminidase [NAG]-to-creatinine and urinary beta-2 microglobulin [beta2MG]-to-creatinine ratios) and UACR were log-transformed in the correlation analysis.

Results: Treatment with TOFO led to similar reductions in glycated haemoglobin (HbA1c) levels, from baseline to week 24, across all groups. The NAG level increased in the normoalbuminuria group and decreased in the macroalbuminuria group significantly (P < .001, both), but did not change in the microalbuminuria group. Significant reductions in the UACR were observed in both microalbuminuria and macroalbuminuria groups (P < .001, both). Significant negative correlations between changes in the NAG and beta2MG levels and their corresponding baseline values were observed in all participants. The reduction in the UACR was negatively correlated with baseline levels. The changes in the tubular indices were positively correlated with reductions in the UACR across groups.

Conclusions: Logarithmic reductions in the renal tubular indices, via SGLT2 inhibition, were observed in patients with T2DM. TOFO may not only improve the degree of albuminuria but may also have protective effects on the tubules.

Keywords: N‐acetyl‐beta‐d‐glucosaminidase; albuminuria; beta‐2 microglobulin; diabetic nephropathy; estimated glomerular filtration rate; sodium‐glucose cotransporter 2; tofogliflozin; tubular glomerular feedback; type 2 diabetes mellitus; urine albumin‐to‐creatinine ratio.