The Effects of Switching from Dipeptidyl Peptidase-4 Inhibitors to Glucagon-Like Peptide-1 Receptor Agonists on Bone Mineral Density in Diabetic Patients

Abstract

Purpose Diabetes increases the risk of fragility fractures. As a result, when choosing a diabetes treatment, whether the drug affects bone density should be taken into account. The goal of this study was to determine how switching from dipeptidyl peptidase-4 inhibitors (DPP-4i) to glucagon-like peptide-1 receptor agonists (GLP-1RA) influenced bone mineral density (BMD) in diabetic patients. Patients and Methods In this retrospective cohort study, diabetic patients with osteoporosis or osteopenia who used DPP-4i but not anti-osteoporosis medications were divided into two groups: those who switched to GLP-1RA (n = 132) and those who did not (control group, n = 133). We compared changes in glycemic control and BMD with and without conversion from DPP-4i to GLP-1RA. Results Prior to switching, there was no difference between the groups in terms of age, gender, glycosylated hemoglobin (HbA1c), or BMD. HbA1c was 8.7% in the participants (mean age 62.7 years, 17.4% female). Despite the fact that there was no difference in femoral neck BMD, the GLP-1RA group had a greater decrease in lumbar spine BMD (−0.028 g/cm 2 versus −0.019 g/cm 2 , p = 0.041) than the control group. Furthermore, HbA1c levels in the GLP-1RA-treated group were considerably lower than in the control group (7.5% versus 8.0%, p = 0.027). Conclusion While switching to GLP-1RA improves glycemic control, it appears to have a less favorable effect on bone density than continuing DPP-4i. More research is needed, however, to determine whether diabetic patients with low bone density should be switched from DPP-4i to GLP-1RA.

The effects of exenatide and insulin glargine treatments on bone turnover markers and bone mineral density in postmenopausal patients with type 2 diabetes mellitus

“…There are conflicting data on this subject, and long-term studies with large groups are needed. [ 30 , 31 ] There was no significant change in BMI and BMD with treatment in the glargine group. Similar to our study, there are studies in the literature showing that BMD does not change with glargine treatment [ 9 ] and there are studies showing that it increases differently with our study.…”

Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes—A Systematic Review

“…Although an improvement of glycemic control and a larger weight loss was observed, the GLP‐1 RA group experienced a more significant decrease in the lumbar spine BMD than the group continuing DPP‐4i treatment (−0.028 g/cm 2 versus −0.019 g/cm 2 , p = 0.041, adjusted for body mass index [BMI]). ( 48 ) However, in the study examining bone turnover markers, a 6‐month exposure to exenatide in people with T1D did not result in any changes in BMD, as assessed through measurements of the whole body, hip, lumbar spine, and forearm. ( 42 ) Furthermore, in a trial involving obese people without diabetes who were on antipsychotic treatment, a 3‐month exposure to exenatide did not lead to any changes in BMD in the lumbar spine, femoral neck, or total hip.…”

Effect of incretins on skeletal health

“…However, an observational study evaluating the switch in treatment from DPP4-i to GLP-1 RA report an improved glycemic status but significantly decreased lumbar spine BMD in patients switching to GLP-1 RA compared to patients staying on DPP4-i treatment [38 ▪ ]. Although the groups had similar body mass index, HbA1c and BMD at baseline there may be some residual confounding in relation to which patients switched from DPP4-i to GLP-1 RA [38 ▪ ]. This is in contrast to previous studies where patients with type 2 diabetes treated with GLP-1 RA preserved hip and lumbar spine BMD compared to placebo in spite of a weight loss in the active treated group [39], and obese women treated with GLP-1 RA preserved bone mineral content, based on whole body scans, despite a 12% weight loss [40].…”

“…A recent systematic review including data from meta-analyses, randomized controlled trials, and observational studies concluded that treatment with GLP-1 RA does not impact BMD [37]. However, an observational study evaluating the switch in treatment from DPP4-i to GLP-1 RA report an improved glycemic status but significantly decreased lumbar spine BMD in patients switching to GLP-1 RA compared to patients staying on DPP4-i treatment [38 ▪ ]. Although the groups had similar body mass index, HbA1c and BMD at baseline there may be some residual confounding in relation to which patients switched from DPP4-i to GLP-1 RA [38 ▪ ].…”