Effects of Evogliptin and Dapagliflozin on Bone and Glucose Metabolism in Postmenopausal Women with Type 2 Diabetes: A Multicenter Randomized Exploratory Clinical Trial

BACKGROUND: Postmenopausal women with type 2 diabetes mellitus (T2DM) are at increased risk of fragility fractures, emphasizing the importance of selecting antidiabetic agents that support glycemic control and bone health. Most dipeptidyl peptidase-4 inhibitors have shown neutral or favorable effects on bone metabolism; however, data specifically on evogliptin remain limited. This study evaluated the effects of evogliptin and dapagliflozin on bone metabolism and glycemic parameters in postmenopausal women with T2DM. METHODS: This multicenter, randomized clinical trial enrolled postmenopausal women with T2DM assigned to receive evogliptin or dapagliflozin for 48 weeks. The primary outcome was change in bone mineral density (BMD). Glycemic indices were the secondary endpoints. RESULTS: Sixty participants were included in the final analysis, with 30 in each group. After 48 weeks, the change in BMD at the L1-L4 spine and total hip did not differ significantly between groups. Femoral neck BMD decreased significantly in the dapagliflozin group compared with the evogliptin group, although the absolute between-group difference was small (0.00 ± 0.02 vs -0.02 ± 0.04 g/cm², p = 0.0402). After adjustment for baseline femoral neck BMD and 25OHD, the between-group difference was attenuated (p = 0.0763). The body mass index (BMI) decreased more in the dapagliflozin group than in the evogliptin group. In analyses of factors associated with femoral neck BMD change, no statistically significant predictors were identified, although decreasing BMI showed a trend toward association. Glycemic indices did not differ significantly between the groups. CONCLUSION: In postmenopausal women with T2DM, BMD remained stable with evogliptin, whereas dapagliflozin was associated with a small reduction in femoral neck BMD, although this finding was weakened after adjustment. These findings provide preliminary evidence regarding the skeletal effects of evogliptin and dapagliflozin and warrant confirmation in larger studies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04706637).