Sitagliptin and risk of fractures in type 2 diabetes: Results from the TECOS Trial

Objective Type 2 diabetes is associated with increased fracture risk, further elevated by treatments such as thiazolidinediones and sodium-glucose co-transporter-2 inhibitors. As data regarding dipeptidyl peptidase-4 inhibitors are mixed, we examined fracture incidence in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Research Design and Methods We used data from 14,671 TECOS patients randomized double-blind to sitagliptin (n=7332) or placebo (n=7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment examined using multivariable Cox proportional hazards regression. Results Baseline mean (SD) age was 65.5 (8.0) years, diabetes duration 11.6 (8.1) years, HbA1c 7.2% (0.5%) (55.2 mmol/mol [5.5]), with 29.3% of participants women and 32.1% non-White. During 43,222 person-years’ follow-up, 375 (2.6%; 8.7 per 1000 person-years) had a fracture; 146 were major osteoporotic fractures (hip [n=34], upper extremity [n=81], and clinical spine [n=31]). Adjusted analyses showed fracture risk increased independently with older age (p Conclusion Fractures were common among TECOS patients with diabetes, but not related to sitagliptin therapy. Insulin and metformin treatment were associated with increased and decreased fracture risks, respectively.