Endocrinol Metab.  2021 Aug;36(4):895-903. 10.3803/EnM.2021.1026.

Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus

• Ha J
• Lim Y
• Kim MK
• Kwon HS
• Song KH
• Ko SH
• Kang MI
• Moon SD
• Baek KH

• KMID: 2519677
• DOI: http://doi.org/10.3803/EnM.2021.1026

Abstract

Background
Prospective comparative studies on the effects of various antidiabetic agents on bone metabolism are limited. This study aimed to assess changes in bone mass and biochemical bone markers in postmenopausal patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective, multicenter, open-label, comparative trial included 264 patients with T2DM. Patients who had received a metformin, or sulfonylurea/metformin combination (Group 1); a thiazolidinedione combination (Group 2); a dipeptidyl peptidase-4 inhibitor (gemigliptin) combination (Group 3); or an sodium-glucose cotransporter 2 inhibitor (empagliflozin) combination (Group 4) were prospectively treated for 12 months; bone mineral density (BMD) and bone turnover marker (BTM) changes were evaluated.
Results
The femoral neck BMD percentage changes were −0.79%±2.86% (Group 1), −2.50%±3.08% (Group 2), −1.05%±2.74% (Group 3), and −1.24%±2.91% (Group 4) (P<0.05). The total hip BMD percentage changes were −0.57%±1.79% (Group 1), −1.74%±1.48% (Group 2), −0.75%±1.87% (Group 3), and −1.27%±1.72% (Group 4) (P<0.05). Mean serum BTM (C-terminal type 1 collagen telopeptide and procollagen type 1 amino-terminal propeptide) levels measured during the study period did not change over time or differ between groups.
Conclusion
Significant bone loss in the femoral neck and total hip was associated with thiazolidinedione combination regimens. However, bone loss was not significantly associated with combination regimens including gemigliptin or empagliflozin. Caution should be exercised during treatment with antidiabetic medications that adversely affect the bone in patients with diabetes at a high risk of bone loss.

Keyword

Osteoporosis; Diabetes mellitus; Bone density; Thiazolidinediones; Sodium-glucose transporter 2 inhibitors

Figure

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  Fig. 1 Enrollment, randomization, and follow-up of participants. T2DM, type 2 diabetes mellitus; DPP4i, dipeptidyl peptidase-4 inhibitor; SGLT2i, sodium-glucose cotransporter 2 inhibitor.

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  Fig. 2 Percentage change of bone mineral density (BMD) from baseline to 12 months. (A) Lumbar spine, (B) femoral neck, (C) total hip. Group 1, metformin or metformin/sulfonylurea combination; Group 2, thiazolidinedione with metformin and/or sulfonylurea combination; Group 3, dipeptidyl peptidase 4 inhibitor with metformin and/or sulfonylurea combination; Group 4, sodium-glucose cotransporter 2 inhibitors with metformin and/or sulfonylurea combination. aP<0.05 compared with Group 1, 3, and 4; bP<0.05 compared with baseline; cP<0.05 compared with Group 1 and 3.

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