Patients with type 2
diabetes mellitus (T2DM) appear to have increased risk for fractures. In this context, the finding that
canagliflozin, a
sodium-
glucose co-transporter-2 (SGLT) inhibitor, increased the risk for fracture compared with placebo in the
Canagliflozin Cardiovascular Assessment Study (CANVAS), a large randomized controlled trial (RCT) in patients with established
cardiovascular disease or multiple cardiovascular risk factors, created concern. In the present review, we summarize the data regarding the association between
SGLT2 inhibitors and fracture risk in patients with T2DM. In contrast to the findings reported in CANVAS,
canagliflozin did not affect the risk of fracture in a more recent, large RCT in patients with
diabetic nephropathy. In addition,
empagliflozin and
dapagliflozin, other members of this class, also do not appear to affect the incidence of fracture. Moreover, there is no clear pathogenetic mechanism through which
SGLT2 inhibitors increase the risk for fractures. Therefore, available data are inconclusive to attribute to these drugs a direct responsibility for
bone fractures.