Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucose-lowering drugs that increase urinary glucose excretion have been shown to reduce CV events in patients with type 2 diabetes (T2D). Furthermore, several studies have demonstrated that treatment with SGLT2 inhibitors affect calcium and phosphate homeostasis, but the effect of empagliflozin on these biomarkers is hitherto not investigated in detail.

Aim: This post-hoc analysis of the EMPA hemodynamics study examined effects of empagliflozin on calcium and phosphate homeostasis.

Methods: In this placebo-controlled, randomized, double-blind study patients with T2D were randomized to empagliflozin 10 mg (n=20) or placebo (n=22). Biomarkers of calcium and phosphate homeostasis were assessed before, and after 3 days and 3 months of treatment.

Results: After 3 days of treatment empagliflozin significantly increased serum levels of phosphate (baseline: 1.10 ± 0.21 mmol/L; day 3: 1.25 ± 0.23 mmol/L; p=0.036), parathyroid hormone (PTH) (baseline: 57.40 ± 30.49 pg/mL; day 3: 70.23 ± 39.25 pg/mL; p=0.025), fibroblast growth factor 23 (FGF23) (baseline: 77.92 ± 24.31 pg/mL; day 3: 109.18 ± 58.20 pg/mL; p=0.001) and decreased 1,25-dihydroxyvitamin D (baseline: 35.01 ± 14.01 ng/L; day 3: 22.09 ± 10.02 mg/L; p<0.001), while no difference of these parameters was recorded after 3 months of treatment. Empagliflozin had no significant effects on serum calcium and markers of bone resorption (collagen type 1 β-carboxy-telopeptide = β-CTX) or formation (osteocalcin) after 3 days and 3 months of treatment.

Conclusions: Empagliflozin treatment of patients with T2D transiently increases serum phosphate, PTH and FGF23, and decreases 1,25-dihydroxyvitamin D. This might reflect a temporal increase of sodium driven phosphate reabsorption in the proximal tubule of the kidney caused by increased sodium availability in response to SGLT2 inhibition.