Sitagliptin and risk of fractures in type 2 diabetes: Results from the TECOS trial.
To examine fracture incidence among participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).



We used data from 14 671 participants in the TECOS study who were randomized double-blind to sitagliptin (n = 7332) or placebo (n = 7339). Cumulative fracture incidence rates were calculated and their association with study treatment assignment was examined using multivariable Cox proportional hazards regression.



The baseline mean (standard deviation) participant age was 65.5 (8.0) years, diabetes duration was 11.6 (8.1) years and glycated haemoglobin level was 7.2 (0.5)% [55.2 (5.5) mmol/mol], and 29.3% of participants were women and 32.1% were 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 < .001), female sex (P < .001), white race (P < .001), lower diastolic blood pressure (P < .001) and diabetic neuropathy (P = .003). Sitagliptin, compared with placebo, was not associated with a higher fracture risk [189 vs 186 incident fractures: unadjusted hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.82 to 1.23, P = .944; adjusted HR 1.03, P = .745], major osteoporotic fractures (P = .673) or hip fractures (P = .761). Insulin therapy was associated with a higher fracture risk (HR 1.40, 95% CI 1.02-1.91; P = .035), and metformin with a lower risk (HR 0.76, 95% CI 0.59-0.98; P = .035).



Fractures were common among people with diabetes in the TECOS study, but were not related to sitagliptin therapy. Insulin and metformin treatment were associated with higher and lower fracture risks, respectively.
St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Robert G
RG
Josse
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Sumit R
SR
Majumdar
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
Yinggan
Y
Zheng
Wolfson Diabetes and Endocrine Clinic, Addenbrooke's Hospital, Cambridge University Hospitals Foundation Trust, Cambridge, UK.
Amanda
A
Adler
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
M Angelyn
MA
Bethel
University of North Carolina School of Medicine, Chapel Hill.
John B
JB
Buse
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Jennifer B
JB
Green
Merck & Co., Inc., Kenilworth, New Jersey.
Keith D
KD
Kaufman
Endocrine and Metabolic Consultants, Rockville, Maryland.
Helena W
HW
Rodbard
Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria.
Tsvetalina
T
Tankova
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
Cynthia M
CM
Westerhout
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Eric D
ED
Peterson
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Rury R
RR
Holman
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
Paul W
PW
Armstrong
D000367:Age Factors; D000368:Aged; D001793:Blood Preservation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000453:epidemiology / Q000209:etiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006620:Hip Fractures / Q000453:epidemiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000453:epidemiology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D044465:White People
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human
DPP-4 inhibitors; diabetes; fractures; sitagliptin