Original ArticlesComparison Of The Long-Term Effects Of Liraglutide And Glimepiride Monotherapy On Bone Mineral Density In Patients With Type 2 Diabetes
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INTRODUCTION
Patients with type 2 diabetes, particularly postmenopausal women, are at increased risk for fragility fractures (1–4). This occurs despite type 2 diabetes being associated with a higher bone mineral density (BMD) (5).
Although BMD is useful to predict fracture risk in the general population, the relation of BMD and fracture risk in patients with type 2 diabetes is unclear. A recent study reported that rosiglitazone reduced BMD and increased bone turnover in postmenopausal women with type 2
METHODS
This study was a subgroup analysis from the LEAD-3 trial, in which assessment of total BMD at baseline, week 52, and week 104 was optional. Detailed methods for the LEAD-3 study have been previously published (20). Briefly, the study was a double-blind, double-dummy, active-control, parallel-group, phase III clinical trial that investigated the safety and efficacy of two doses of liraglutide (1.2 and 1.8 mg/day) versus glimepiride for treatment of type 2 diabetes. A total of 138 sites (126 in
Serum Calcium and Fractures
In the trial as a whole, there was minor variation in serum calcium and phosphatase levels in each treatment group throughout the study. At 104 weeks (n = 14, 13, and 9, respectively), mean serum calcium levels were 2.34 (0.12), 2.36 (0.11), and 2.32 (0.07) mmol/L (SD) in the liraglutide 1.8 mg, liraglutide 1.2 mg, and glimepiride groups, with mean changes from baseline of -0.10 (0.12), -0.11 (0.11), and -0.13 (0.14) mmol/L (SD), respectively. Mean phosphatase levels were 88.79 (30.67), 87.46
DISCUSSION
Given the increased risk of fractures in patients with type 2 diabetes, it is of interest to examine the effects of new antidiabetic therapies on BMD. In this small, first long-term analysis of liraglutide monotherapy, no decline in total BMD was observed in patients with type 2 diabetes over a 2-year treatment period. There was no notable difference in change in BMD over this period between liraglutide and glimepiride. Significant weight loss is associated with notable decreases in BMD, as
CONCLUSION
Further studies, including those measuring regional BMD, are needed to extend the findings of the present study to a larger population of patients with type 2 diabetes and to determine whether liraglutide or other incretin therapies are associated with a reduced risk of fracture in patients with type 2 diabetes.
DISCLOSURE
M.P.G. has no conflicts of interest to report. M.M. has attended advisory panels for Novo Nordisk, Sanofi, Servier; and is a board member for Eli Lilly & Co and Merck. J.J.H. is a consultant for Novo Nordisk and has attended advisory panels for Novo Nordisk. A.J.G. has attended advisory panels for Novo Nordisk, Daiichi Sankyo, Merck, Takeda, LipoScience, and Boehringer Ingelheim; has acted as a consultant for Novo Nordisk, Daiichi Sankyo, Merck, Santarus, Takeda, LipoScience, Boehringer
ACKNOWLEDGMENT
We acknowledge the important contribution of our friend and colleague Michaela Diamant, who was involved in manuscript preparation and sadly died before this paper was completed. The study (ClinicalTrials.gov NCTC00294723) was funded by Novo Nordisk, the manufacturer of liraglutide. Editorial assistance was provided by Watermeadow Medical, funded by Novo Nordisk.
Author contributions: M.G., M.M., J.H., A.G., F.B., H.T., and R.P. contributed to the writing, revisions, critical review, and
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