Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks

Abstract

BackgroundThe aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.MethodsA 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).ResultsDuring the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.ConclusionOur results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

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The use of metformin, insulin, sulphonylureas, and thiazolidinediones and the risk of fracture: Systematic review and meta‐analysis of observational studies

“…Furthermore, the underlying mechanism by which thiazolidinediones may increase the risk of fracture did not appear to be explained by the effect of these medications on bone turnover markers . Notably, 52 weeks of treatment with 0.5 mg of lobeglitazone, a novel thiazolidinedione that has been approved in South Korea did not appear to have a negative effect on BMD in the femoral neck and total hip compared with the placebo . Limited evidence from RCTs has indicated that the negative effects of thiazolidinediones on bone may not worsen after the discontinuation of use, suggesting causality between these medications and bone health.…”

Diabetes pharmacotherapy and effects on the musculoskeletal system

“…Interestingly, the newer TZD, lobeglitazone, when compared with placebo over a 52‐week treatment period, was not associated with a significant decrease in BMD in 112 adults with T2D (mean age ~56 years; duration of T2D ~4 years); however, these relatively better skeletal outcomes need to be confirmed with further studies, as there are no long‐term data yet available.…”