Abstract: FR-OR093

Effects of SGLT2 Inhibition on Fibroblast Growth Factor 23 and 25(OH) Vitamin D

Session Information

Category: Diabetes

  • 502 Diabetes Mellitus and Obesity: Clinical

Authors

  • de Jong, Maarten A., University Medical Center Groningen, Groningen, Netherlands
  • Petrykiv, Sergei, University Medical Center Groningen, Groningen, Netherlands
  • Laverman, Gozewijn Dirk, ZGT Almelo, Almelo, Overijssel, Netherlands
  • de Zeeuw, Dick, University Medical Center Groningen, Groningen, Netherlands
  • Bakker, Stephan J.L., University Medical Center Groningen, Groningen, Netherlands
  • Lambers Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands
  • De Borst, Martin H., University Medical Center Groningen, Groningen, Netherlands
Background

Sodium glucose co-transporter 2 (SGLT2) inhibitors like dapagliflozin are novel drugs for the treatment of diabetes mellitus, which also promise to slow the progression of kidney disease. Previous studies found that SGLT2 inhibition increases serum phosphate and PTH. However, the effects on fibroblast growth factor 23 (FGF23) and vitamin D are less well studied.

Methods

This is a post-hoc analysis of a double-blind, randomized, cross-over trial, enrolling patients on stable RAAS blockade, albumin:creatinine ratio between 100 and 3500 mg/g, eGFR ≥ 45 ml/min/1.73m2 and HbA1c ≥ 55 and <100 mmol/mol. Patients were treated with dapagliflozin 10 mg/d (DAPA) or placebo during 2 consecutive periods of 6 weeks each, with a 6-week wash-out in between. Plasma C-terminal FGF23 was measured with ELISA (Immutopics Inc), 25(OH) vitamin D with LC-MS/MS. Data are shown as mean (95%CI). Endpoints were assessed with linear mixed models.

Results

Thirty-three patients (age 61±9 yrs; 24% female; median 24h UAE 470 mg/24hr) completed the study. Baseline characteristics and results are shown in table 1. DAPA increased serum phosphate, PTH and FGF23 compared to both baseline and placebo. Serum calcium and 25(OH)D did not change (p=0.9, p=0.8). DAPA reduced eGFR, but change in eGFR and change in bone and mineral parameters were not correlated (all P>0.5). All effects of DAPA were reversed 6 weeks after discontinuation.

Conclusion

Dapagliflozin treatment induced a significant rise in serum phosphate, PTH and FGF23 levels, independent of concomitant effects on eGFR. Serum calcium and 25(OH)D levels remained unchanged. In light of the high prevalence of bone and mineral disorders in patients with diabetes and kidney disease, future studies should assess the clinical significance of these alterations.

Plasma parameterBaselineΔ PlaceboΔ DAPA
Phosphate (mg/dL)3.37 (3.19;5.59)0.03 (-0.12;0.19)0.25 (0.09;0.40)*‡
PTH (pg/mL)48.3 (40.5;55.4)1.9 (-2.2;6.1)10.4 (5.7;14.1)*‡
FGF23 (RU/mL)124.3 (100.6;153.6)4.9% (-5.3;16.2%)24.9% (12.3;38.8%)*‡
Calcium (mg/dL)9.42 (9.26;9.58)0.06(-0.04;0.20)0.06 (-0.04;0.19)
25(OH)D (ng/mL)19.29 (16.21;22.37)-1.44 (-3.27;0.39)-1.25 (-3.13;0.63)
eGFR (ml/min*1.73m2)69.7 (63.5;76.4)0.9 (-1.6;3.4)-4.4 (-7.0;-1.9)*‡

Table 1: baseline values and mean change (95%CI) vs. baseline during Dapa and Placebo study periods. * denotes P < 0.01 vs baseline. ‡ denotes P< 0.01 vs placebo.

Funding

  • Commercial Support