Sodium-Glucose Cotransporter 2 Inhibitors vs Incretin-Based Drugs and Risk of Fractures for Type 2 Diabetes

Abstract

This cohort study assesses the risk of fractures associated with sodium-glucose cotransporter 2 inhibitors vs incretin-based drugs of dipeptidyl-peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists, separately, in postmenopausal individuals with type 2 diabetes.

Key Points

Question

Do sodium-glucose cotransporter 2 inhibitors (SGLT2i) increase the risk of fractures among postmenopausal individuals with type 2 diabetes?

Findings

In this Korean nationwide cohort study among the population susceptible for bone fragility, SGLT2i was not associated with the increased risk of fractures compared with the incretin-based drugs of dipeptidyl-peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists, separately.

Meaning

In this study, SGLT2i use was associated with either similar or lower risks of fractures than incretin-based drugs even in a population with high risk of fractures.

Abstract

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.