Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: An updated meta‐analysis

Abstract

Background The aim of the study is to update and determine the effects of sodium glucose cotransporter 2 (SGLT2) inhibitor therapy on fracture and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). Methods We identified 27 eligible randomized controlled trials (RCTs) that compared the efficacy and safety of SGLT2 inhibitors to a placebo in 20 895 T2DM participants, with an average duration of 64.22 weeks. The relative risk (RR) of bone fracture and weighted mean difference (WMD) of changes in the BMD from baseline were determined to evaluate the risk of fracture. The degree of heterogeneity was evaluated by the I2 statistic, and publication bias was estimated using a funnel plot and Egger test. Results The pooled RR was 1.02 (95% CI [0.81, 1.28]) with low heterogeneity, indicating that SGLT2 inhibitor treatment was not correlated with a higher risk of fracture. Additionally, no increased risk was found for patients with different ages, sexes, and levels of HbA1c and some biochemical indicators. Three trials with 1303 patients reported a change in the BMD from baseline. SGLT2 inhibitor treatment did not decrease the BMD at four skeletal sites (lumbar spine, femoral neck, total hip, and distal forearm), and the overall WMD was 0.08 (95% CI [−0.09, 0.26]). No significant publication bias was detected. Conclusions No increased risk for bone fracture was detected in patients with T2DM treated with SGLT2 inhibitors in this meta‐analysis. SGLT2 inhibitor therapy did not appear to affect bone health, but more long‐term detailed data are needed to validate this conclusion.

Bone health in diabetes and prediabetes

“…Furthermore, increased bone turnover and reduced total hip BMD have been reported in patients with T2D treated with canagliflozin[214]. Nevertheless, recent population studies and metanalyses including several thousands of patients consistently failed to demonstrate an association between SGLT2 inhibitor treatment and increased fracture risk in patients with T2D[215-219].…”

Sodium-Glucose Co-Transporter 2 Inhibitors and Fracture Risk

“…In another recent meta-analysis of 27 randomized controlled trials (n = 20,895), SGLT2 inhibitors did not increase the risk of fracture compared with placebo (relative risk 1.02, 95% CI 0.81-1.28) [29]. In groups at higher risk for fracture, including women and the elderly, no increase in the incidence of fracture was noted either [29]. Moreover, three trials (n = 1303) evaluated the effects of SGLT2 inhibitors on BMD and did not show any change in the evaluated skeletal sites (lumbar spine, femoral neck, total hip, and distal forearm) ( Table 3) [29].…”

“…In another recent meta-analysis of 27 randomized controlled trials (n = 20,895), SGLT2 inhibitors did not increase the risk of fracture compared with placebo (relative risk 1.02, 95% CI 0.81-1.28) [29]. In groups at higher risk for fracture, including women and the elderly, no increase in the incidence of fracture was noted either [29].…”

“…In groups at higher risk for fracture, including women and the elderly, no increase in the incidence of fracture was noted either [29]. Moreover, three trials (n = 1303) evaluated the effects of SGLT2 inhibitors on BMD and did not show any change in the evaluated skeletal sites (lumbar spine, femoral neck, total hip, and distal forearm) ( Table 3) [29].…”

Therapie des Typ-2-Diabetes

“…Eine aktuelle Frakturanalyse von Menschen mit Typ-2-Diabetes (n≥ 12 000), die mit Empagliflozin behandelt wurden (gepoolte Daten aus placebokontrollierten Studien und einer Head-to-Head-Studie vs. Glimepirid), ergab keine signifikant erhöhte Rate von Frakturen [108]. Zahlreiche Metaanalysen zeigten auch keine signifikante Erhöhung der Frakturraten unter der Therapie mit SGLT2-Hemmern [109][110][111].…”