Hwa Yeon Ko, PharmD1; Sungho Bea, PharmD1; Han Eol Jeong, MPH, PhD1,2; Sohee Park, PharmD, PhD1,3; Young Min Cho, MD, PhD4,5; Sung Hye Kong, MD6; Ju-Young Shin, PhD1,2,7
1School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
2Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
3Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom
4Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
5Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
6Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
7Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea
Drs Ko and Bea contributed equally to this work as co–first authors.
Corresponding Author: Ju-Young Shin, PhD
Importance Postmenopausal individuals with type 2 diabetes are susceptible to fractures due to the interaction of elevated blood glucose levels and a deficiency of the hormone estrogen. Despite continued concerns of fracture risks associated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), existing evidence in this high-risk population is lacking.
Objective To assess the risk of fractures associated with SGLT2i vs incretin-based drugs of dipeptidyl-peptidase 4 inhibitors (DPP4i) and glucagon-like peptide 1 receptor agonists (GLP1RA), separately, in postmenopausal individuals with type 2 diabetes.
Design, Setting, and Participants This active-comparator, new-user cohort study used nationwide claims data of Korea and took place from January 1, 2013, to December 31, 2020. Postmenopausal individuals (aged ≥45 years) with type 2 diabetes were included.
Exposures New users of SGLT2i or comparator drugs.
Main Outcomes and Measures The primary outcome was overall fractures, comprising vertebral, hip, humerus, and distal radius fractures. Patients were followed up from the day after drug initiation until the earliest of outcome occurrence, drug discontinuation (90-day grace period) or switch, death, or end of the study period. After propensity score fine stratification, hazard ratios (HRs) with 95% CIs were estimated using weighted Cox models.
Results Among 37 530 (mean [SD] age, 60.6 [9.7] years) and 332 004 (mean [SD] age, 60.6 [9.9] years) new users of SGLT2i and DPP4i, respectively, a lower rate of incident overall fractures was presented with SGLT2i vs DPP4i (weighted HR, 0.78; 95% CI, 0.72-0.84). Among 111 835 (mean [SD] age, 61.4 [9.8] years) and 8177 (mean [SD] age, 61.1 [10.3] years) new users of SGLT2i and GLP1RA, respectively, no association with an increased risk of overall fractures was presented with SGLT2i vs GLP1RA (weighted HR, 0.92; 95% CI, 0.68-1.24). Results from several subgroup and sensitivity analyses presented consistent results from main analysis.
Conclusions and relevance This population-based cohort study suggests that SGLT2i was not associated with an increased rate of incident fractures compared with DPP4i and GLP1RA, separately, among postmenopausal individuals with type 2 diabetes.