Elsevier

Endocrine Practice

Volume 22, Issue 4, April 2016, Pages 406-411
Endocrine Practice

Original Articles
Comparison Of The Long-Term Effects Of Liraglutide And Glimepiride Monotherapy On Bone Mineral Density In Patients With Type 2 Diabetes

https://doi.org/10.4158/EP15758.ORGet rights and content

ABSTRACT

Objective: Patients with type 2 diabetes have an increased risk of fragility fractures; the cause is unclear but is likely multifactorial. Some diabetes treatments induce bone loss, accentuating underlying skeletal fragility and increasing fracture risk. This subgroup analysis aimed to compare long-term effects of liraglutide and glimepiride on bone mineral density (BMD) in patients with type 2 diabetes.

Methods: LEAD-3, a 52-week, double-blind, activecontrol, phase III, multicenter trial, investigated the efficacy of liraglutide (1.2 and 1.8 mg/day) versus glimepiride monotherapy in type 2 diabetes. A 52-week, open-label extension followed, in which participants remained on randomized therapy. A subgroup of participants underwent BMD measurement by dual-energy X-ray absorptiometry at baseline, 52, and 104 weeks. The main outcome measure was change from baseline in total body BMD at 52 and 104 weeks, assessed by analysis of covariance.

Results: A total of 746 patients with type 2 diabetes aged 19 to 79 years were randomized into the main trial. Of these, 61 patients (20 assigned to liraglutide 1.8 mg/day, 23 to liraglutide 1.2 mg/day, 18 to glimepiride 8 mg/day) had BMD measurements. Baseline age, body mass index, diabetes duration, glycated hemoglobin, and total BMD were similar across treatment groups. There was no apparent difference in mean total BMD change from baseline in patients receiving liraglutide 1.8 or 1.2 mg/day or glimepiride 8 mg/day at 52 or 104 weeks.

Conclusion: In this small subgroup analysis, liraglutide monotherapy did not negatively affect total BMD in a 2-year prospective study, suggesting it may not exacerbate the consequences of bone fragility.

Abbreviations:

BMD = bone mineral density

BMI = body mass index

DPP-4 = dipeptidyl peptidase-4

DXA = dual-energy X-ray absorptiometry

GLP-1RA = glucagon-like peptide 1 receptor agonist

LEAD = Liraglutide Effect and Action in Diabetes

TZD = thiazolidinedione

Section snippets

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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