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

Abstract

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±0.24% vs. 7.40±0.16%, P=0.007), dulaglutide (8.77±0.37% vs. 7.06±0.28%, P<0.001), and insulin glargine (8.57±0.24% vs. 7.23±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.