Patients with type 2 diabetes mellitus appear to have increased risk for fractures. |
Canagliflozin, a sodium-glucose co-transporter-2 (SGLT) inhibitor, increased the risk for fracture compared with placebo in a large randomized controlled trial (RCT) in patients with established cardiovascular disease or multiple cardiovascular risk factors but not in a more recent, large RCT in patients with diabetic nephropathy. |
Empagliflozin and dapagliflozin, other members of this class, also do not appear to affect the incidence of fracture. |
There is no clear pathogenetic mechanism through which SGLT2 inhibitors increase the risk for fractures. |
Overall, available data are inconclusive to attribute to SGLT2 inhibitors a direct responsibility for bone fractures. |
Introduction
Search Strategy
T2DM and Fractures
References | n | Major findings | Comments |
---|---|---|---|
[11] | 6655 | Patients with T2DM had increased nonvertebral fracture risk than subjects without T2DM (hazard ratio 1.33, 95% confidence interval 1.00–1.77) | Patients with T2DM had higher bone mineral density than subjects without T2DM The increased fracture risk was present only in treated patients with T2DM and not in newly diagnosed patients |
[12] | 996 | T2DM was an independent risk factor for prevalent vertebral fracture | Bone mineral density was not associated with the presence of vertebral fracture in patients with T2DM |
SGLT2 Inhibitors and Fracture Risk
References | Trial | n | Inclusion criteria | Age (years) | Female (%) | BMI (kg/m2) | T2DM duration (years | Follow-up (years) | Fracture risk |
---|---|---|---|---|---|---|---|---|---|
[7] | CANVAS | 10,142 | Established CVD or age ≥ 50 years with ≥ 2 cardiovascular risk factors | 63 | 36 | 32.0 | 13.5 | 2.4 | HR 1.26, 95% CI 1.04–1.52 |
[26] | CREDENCE | 4401 | Chronic kidney disease | 63 | 34 | 31.3 | 15.8 | 2.6 | HR 0.98, 95% CI 0.70–1.37 |
[8] | DECLARE-TIMI 58 | 17,160 | Established CVD or multiple cardiovascular risk factors | 64 | 37 | 32.0 | 10.5 | 4.2 | HR 1.04, 95% CI 0.91–1.18 |
[27] | DAPA-HF | 1983 | New York Heart Association class II, III, or IV heart failure and ejection fraction ≤ 40% | 66 | 23 | 28.2 | NR | 1.8 | 2.1% in both placebo and dapagliflozin group |
[9] | EMPA-REG OUTCOME | 7020 | Established CVD | 63 | 29 | 30.6 | NR | 3.1 | 3.9% and 3.8% in the placebo and empagliflozin group, respectively |
References | Number of studies | Number of patients | Major findings | Comments |
---|---|---|---|---|
[28] | 30 | 23,372 | Similar incidence of bone fractures in patients receiving SGLT2 inhibitors and placebo | When the effects of canagliflozin, dapagliflozin, and empagliflozin on fractures were analyzed separately, none was associated with increased risk for fracture |
[29] | 27 | 20,895 | Similar incidence of bone fractures in patients receiving SGLT2 inhibitors and placebo | In groups at higher risk for fracture, including women and the elderly, no increase in the incidence of fracture was noted in patients treated with SGLT2 inhibitors |