SGLT2i use and fracture risk compared with DPP4i in patients with T2DM
- 1School of Post‐Baccalaureate Medicine, College of Medicine Kaohsiung Medical University Kaohsiung Taiwan
- 2Division of Adult Reconstruction Surgery, Department of Orthopedics, Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan
- 3Institute of Health and Welfare Policy, College of Medicine National Yang Ming Chiao Tung University Taipei Taiwan
Abstract
Introduction The association between sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) use and fracture risk remains inconclusive. Most previous studies have focused on treatment‐naïve patients, despite many patients in routine clinical practice initiating SGLT2i therapy after prior dipeptidyl peptidase‐4 inhibitor (DPP4i) use. This study aimed to evaluate the risk of fractures associated with SGLT2i compared with dipeptidyl peptidase‐4 inhibitors (DPP4i) in Taiwan. Materials and Methods This nationwide cohort study used Taiwan's National Health Insurance Research Database. Patients with T2DM initiating SGLT2i or DPP4i therapy between 2016 and 2019 were identified. Follow‐up began one year after the index date to ensure adequate treatment exposure before outcome assessment. A prevalent new‐user design and 1:2 propensity score matching (PSM) were applied to balance baseline characteristics. Fractures were ascertained from medical claims, and competing risk regression was used to estimate fracture risk, accounting for death as a competing event. Results After PSM, 106,992 SGLT2i users and 213,984 DPP4i users were included with comparable baseline profiles. Over a mean follow‐up of 3.5 years, the overall risk of any fracture did not differ between groups. Although SGLT2i use was associated with a significantly lower risk of hip fracture compared with DPP4i use (subdistribution hazard ratio = 0.89, 95% CI: 0.81–0.98), this association was no longer statistically significant after adjustment for multiple comparisons. Subgroup analyses yielded generally consistent findings. Conclusions In this cohort, SGLT2i use was not associated with increased overall or major osteoporotic fracture risk vs DPP4i. The prevalent new‐user design captures prior treatment histories and reflects real‐world practice.
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BibTeX
@article{lin2026sglt2i,
title = {{SGLT2i use and fracture risk compared with DPP4i in patients with T2DM}},
author = {Sung‐Yen Lin and Shih‐Hao Huang and Ching‐Han Chiang and Cheng‐Jung Ho and Chung‐Hwan Chen and Li‐Nien Chien},
journal = {Journal of Diabetes Investigation},
year = {2026},
month = nov,
doi = {10.1111/jdi.70433},
url = {https://doi.org/10.1111/jdi.70433},
note = {CC BY},
}
RIS
TY - JOUR
TI - SGLT2i use and fracture risk compared with DPP4i in patients with T2DM
AU - Sung‐Yen Lin
AU - Shih‐Hao Huang
AU - Ching‐Han Chiang
AU - Cheng‐Jung Ho
AU - Chung‐Hwan Chen
AU - Li‐Nien Chien
PY - 2026
DA - 2026/11/02
JO - Journal of Diabetes Investigation
DO - 10.1111/jdi.70433
UR - https://doi.org/10.1111/jdi.70433
AB - Introduction The association between sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) use and fracture risk remains inconclusive. Most previous studies have focused on treatment‐naïve patients, despite many patients in routine clinical practice initiating SGLT2i therapy after prior dipeptidyl peptidase‐4 inhibitor (DPP4i) use. This study aimed to evaluate the risk of fractures associated with SGLT2i compared with dipeptidyl peptidase‐4 inhibitors (DPP4i) in Taiwan. Materials and Methods This nationwide cohort study used Taiwan's National Health Insurance Research Database. Patients with T2DM initiating SGLT2i or DPP4i therapy between 2016 and 2019 were identified. Follow‐up began one year after the index date to ensure adequate treatment exposure before outcome assessment. A prevalent new‐user design and 1:2 propensity score matching (PSM) were applied to balance baseline characteristics. Fractures were ascertained from medical claims, and competing risk regression was used to estimate fracture risk, accounting for death as a competing event. Results After PSM, 106,992 SGLT2i users and 213,984 DPP4i users were included with comparable baseline profiles. Over a mean follow‐up of 3.5 years, the overall risk of any fracture did not differ between groups. Although SGLT2i use was associated with a significantly lower risk of hip fracture compared with DPP4i use (subdistribution hazard ratio = 0.89, 95% CI: 0.81–0.98), this association was no longer statistically significant after adjustment for multiple comparisons. Subgroup analyses yielded generally consistent findings. Conclusions In this cohort, SGLT2i use was not associated with increased overall or major osteoporotic fracture risk vs DPP4i. The prevalent new‐user design captures prior treatment histories and reflects real‐world practice.
SN - 2040-1124
SN - 2040-1116
ER -