Adverse effects of SGLT2 inhibitors on bone health

Abstract

Sodium–glucose cotransporter 2 (SGLT2) inhibitors offer attractive metabolic and cardiorenal benefits for patients with type 2 diabetes, but are associated with a number of safety issues. A recent study documented that SGTL2 inhibition indirectly triggers the FGF23/1,25-dihydroxyvitamin D/parathyroid hormone axis, which may contribute to adverse effects on bone health.

Figures

Figure 1. Time course of pharmacodynamic responses to canagliflozin

Healthy volunteers (N=25) were admitted to the NIH Clinical Center to participate in a randomized crossover trial . Research subjects participated in two admissions during which they received either placebo or canagliflozin (300 mg/d) for five days. Each research subject was randomized between placebo or canagliflozin for the first admission, and then crossed over to the other treatment for the second admission. Four blood samples were obtained on each day (8 AM, 10 AM, 12 noon, and 8 PM). The details of the study design are described in Blau et al. We calculated averages of the timed blood samples on each of the five days of the study. This figure presents drug-induced changes of those averages (i.e., placebo-subtracted values) for each day. In order to display all four parameters on the same axes, we expressed the data in the following units: serum phosphorus (mg/L); plasma FGF23 (pg/mL); plasma PTH (pg/mL); and 1,25-dihydroxyvitamin D (% of time zero value).