Effects of Metformin Alone or in Combination With Insulin on Bone Mineral Density in Osteopenic Patients With Type 2 Diabetes

Omodele Awoniyi, Spencer Conner, Solomon Solomon


Background: Patients with diabetes are at risk for osteoporotic fractures. We propose to test the hypothesis that treatment of diabetes mellitus with metformin alone or in combination with insulin affects bone mineral density (BMD) in a positive way possibly via the Wnt/beta-catenin pathway.

Methods: We retrospectively reviewed records of veterans at the Memphis Veterans Administration Medical Center (VAMC) with type 2 diabetes on treatment with metformin alone or in combination with insulin found to have osteopenia by dual-energy X-ray absorptiometry (DXA) between 2002 and 2013. Change in BMD over time was compared with age, race and sex matched controls.

Results: Of 1,662 patients with DXA scans, we had two study groups (13 patients on metformin and insulin; 20 on metformin alone). These patients were compared to age, race and sex matched controls not on metformin, insulin or thiazolidinediones (TZDs). On follow-up (1 - 6 years) of both study groups, there was no statistical difference in average BMD over time compared to controls (P = 0.172 in combination group, P = 0.747 in metformin alone group). However, there was improvement in BMD over time at the right and left femoral neck in the metformin alone group compared to control (left femur P = 0.130; right femur P = 0.017).

Conclusions: In this retrospective study, there was a trend towards improvement in BMD in osteopenic patients with type 2 diabetes treated with metformin. The exact mechanism by which metformin exerts positive effects on bone is yet to be fully elucidated. We propose that metformin may promote bone formation by decreasing sclerostin levels, an inhibitor of the Wnt/beta-catenin pathway. Overall, we surmise that the osteo-anabolic effect of metformin on BMD still needs to be further studied in a larger prospective study.

J Endocrinol Metab. 2014;4(4):89-92
doi: http://dx.doi.org/10.14740/jem234w


Type 2 diabetes mellitus; Osteopenia; Bone mineral density; Metformin; Insulin; Wnt; T-score; Fracture

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