Effects of GLP-1 Receptor Agonists on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: A 52-Week Clinical Study

Introduction. Hypoglycemic drugs affect the bone quality and the risk of fractures in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and insulin on bone mineral density (BMD) in T2DM. Methods. In this single-blinded study, a total of 65 patients with T2DM were randomly assigned into four groups for 52 weeks: the exenatide group ( $n=19$ ), dulaglutide group ( $n=19$ ), insulin glargine group ( $n=10$ ), and placebo ( $n=17$ ). General clinical data were collected, and BMD was measured by dual-energy X-ray absorptiometry. Results. Compared with baseline, the glycosylated hemoglobin (HbA1c) decreased significantly in the exenatide ( $8.11\pm 0.24\%$ vs. $7.40\pm 0.16\%$ , $P=0.007$ ), dulaglutide ( $8.77\pm 0.37\%$ vs. $7.06\pm 0.28\%$ , $P<0.001$ ), and insulin glargine ( $8.57\pm 0.24\%$ vs. $7.23\pm 0.25\%$ , $P<0.001$ ) groups after treatment. In the exenatide group, the BMD of the total hip increased. In the dulaglutide group, only the BMD of the femoral neck decreased ( $P=0.027$ ), but the magnitude of decrease was less than that in the placebo group; the BMD of L1-L4, femoral neck, and total hip decreased significantly ( $P<0.05$ ) in the placebo group, while in the insulin glargine group, the BMD of L2, L4, and L1-4 increased ( $P<0.05$ ). Compared with the placebo group, the BMD of the femoral neck and total hip in the exenatide group and the insulin glargine group were increased significantly ( $P<0.05$ ); compared with the exenatide group, the BMD of L4 in the insulin glargine group was also increased ( $P=0.001$ ). Conclusions. Compared with the placebo, GLP-1RAs demonstrated an increase of BMD at multiple sites of the body after treatment, which may not exacerbate the consequences of bone fragility. Therefore, GLP-1RAs might be considered for patients with T2DM. This trial is registered with ClinicalTrials.gov NCT01648582.