title: Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study.
abstract: Type 2 diabetes and osteoporosis are both common, chronic, and increase with age, whereas type 2 diabetes is also a risk factor for major osteoporotic fractures (MOFs). However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin).
  
  
  
  To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study.
  
  
  
  A sitagliptin new user study design employing a nationally representative Unites States claims database of 72 738 insured patients with type 2 diabetes. We used 90-day time-varying sitagliptin exposure windows and controlled confounding by using multivariable analyses that adjusted for clinical data, comorbidities, and time-updated propensity scores.
  
  
  
  We compared the incidence of MOF (hip, clinical spine, proximal humerus, distal radius) in new users of sitagliptin vs nonusers over a median 2.2 years follow-up.
  
  
  
  At baseline, the median age was 52 years, 54% were men, and median A1c was 7.5%. There were 8894 new users of sitagliptin and 63 834 nonusers with a total 181 139 person-years of follow-up. There were 741 MOF (79 hip fractures), with 53 fractures (4.8 per 1000 person-years) among new users of sitagliptin vs 688 fractures (4.0 per 1000 person-years) among nonusers (P = .3 for difference). In multivariable analyses, sitagliptin was not associated with fracture (adjusted hazard ratio 1.1, 95% confidence interval 0.8-1.4; P = .7), although insulin (P < .001), sulfonylureas (P < .008), and thiazolidinedione (P = .019) were each independently associated with increased fracture risk.
  
  
  
  Even in a young population with type 2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type 2 diabetes were associated with increased risk. These data should be considered when making treatment decisions for those with type 2 diabetes at particularly high risk of fractures.
authors.affiliation: Department of Medicine (S.R.M.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Alliance for Health Outcomes Research in Diabetes at the Alberta Diabetes Institute (S.R.M., D.T.E.), Edmonton, Alberta T6G 2G3, Canada; Department of Medicine (R.G.J.), University of Toronto, Toronto, Ontario M5B 1W8, Canada; Li Ka Shing Knowledge Institute (R.G.J.), St Michael's Hospital, Toronto, Ontario M5B 1W8, Canada; and School of Public Health (M.L., D.T.E.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Sumit R
authors.initials: SR
authors.lastname: Majumdar
authors.affiliation: Department of Medicine (S.R.M.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Alliance for Health Outcomes Research in Diabetes at the Alberta Diabetes Institute (S.R.M., D.T.E.), Edmonton, Alberta T6G 2G3, Canada; Department of Medicine (R.G.J.), University of Toronto, Toronto, Ontario M5B 1W8, Canada; Li Ka Shing Knowledge Institute (R.G.J.), St Michael's Hospital, Toronto, Ontario M5B 1W8, Canada; and School of Public Health (M.L., D.T.E.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Josse
authors.affiliation: Department of Medicine (S.R.M.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Alliance for Health Outcomes Research in Diabetes at the Alberta Diabetes Institute (S.R.M., D.T.E.), Edmonton, Alberta T6G 2G3, Canada; Department of Medicine (R.G.J.), University of Toronto, Toronto, Ontario M5B 1W8, Canada; Li Ka Shing Knowledge Institute (R.G.J.), St Michael's Hospital, Toronto, Ontario M5B 1W8, Canada; and School of Public Health (M.L., D.T.E.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Mu
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Medicine (S.R.M.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Alliance for Health Outcomes Research in Diabetes at the Alberta Diabetes Institute (S.R.M., D.T.E.), Edmonton, Alberta T6G 2G3, Canada; Department of Medicine (R.G.J.), University of Toronto, Toronto, Ontario M5B 1W8, Canada; Li Ka Shing Knowledge Institute (R.G.J.), St Michael's Hospital, Toronto, Ontario M5B 1W8, Canada; and School of Public Health (M.L., D.T.E.), University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Dean T
authors.initials: DT
authors.lastname: Eurich
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D058866:Osteoporotic Fractures / Q000453:epidemiology* / Q000209:etiology; D018570:Risk Assessment; D012307:Risk Factors; D000068900:Sitagliptin Phosphate / Q000009:adverse effects* / Q000627:therapeutic use; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione; D000068900:Sitagliptin Phosphate