Short-term effects of dapagliflozin on biomarkers of bone and mineral metabolism in patients with diabetic kidney disease: A prospective observational study

Abstract

Background

There is still a lack of information regarding the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on bone and mineral metabolism in patients with diabetes and chronic kidney disease (CKD). Therefore, we aimed to investigate the effects of SGLT2i in a cohort of patients suffering from diabetic kidney disease (DKD).

Methods

In this prospective observational study, patients with type 2 diabetes and biopsy-proven diabetic nephropathy or presumptive DKD with eGFR levels ≥20 ml/min/1.73m2 and 25-OH vitamin D levels ≥20 ng/dl were included. 41 used SGLT2i (study group) and 39 continued their current treatment regimens (control group). Serum FGF-23, sclerostin, osteoprotegerin (OPG), and hydroxyproline levels were measured at baseline, 1 month and 3 months after treatment.

Results

Mean age of all patients was 67 ± 9.3 years, and 48 (60%) were female. All patients in the study group used dapagliflozin. Taking into account the renal functions at the commencement of the study, the eGFR values for the study group and the control group were 51.2 ± 15.6 and 44.6 ± 16.9 ml/min/1.73m², respectively (p = 0.01). After three months, these values were observed to be 47.4 ± 16.7 and 44.3 ± 18.8 ml/min/1.73m² (p = 0.43), respectively. At baseline, OPG levels were higher in the study group (p = 0.025) but there were no differences between the groups in terms of FGF-23 and sclerostin levels (p = 0.670 and p = 0.467, respectively). Levels of OPG, FGF-23, and sclerostin significantly decreased throughout 3 months of treatment with dapagliflozin (p < 0.001 for all). Hydroxyproline levels also declined but did not reach to statistical significance (p = 0.075). Multiple linear regression models revealed that treatment with SGLT2i was associated with the change in levels of sclerostin (β=0.303, p = 0.011) and OPG (β=0.210, p = 0.010), but not with FGF-23 (β=0.089, p = 0.150).

Conclusions

FGF-23, sclerostin and OPG levels significantly declined after treatment with dapagliflozin for 3 months.