title: No increased risk of cardiovascular events in older adults initiating dipeptidyl peptidase-4 inhibitors vs therapeutic alternatives.
abstract: To compare the cardiovascular (CV) risk associated with dipeptidyl peptidase-4 (DPP-4) inhibitors relative to sulphonylureas (SUs) and thiazolidinediones (TZDs).
  
  
  
  During 2007 to 2013, using Medicare data for beneficiaries aged >65 years, we identified the following 2 cohorts of new-users, who had not been exposed to the drugs being compared in the 6 months before initiation: (1) DPP-4 inhibitor vs SU initiators and (2) DPP-4 inhibitor vs TZD initiators. Using propensity-score-adjusted Cox models accounting for competing risk by death, we estimated the hazard ratios (HRs), risk differences and 95% confidence intervals (CIs) for myocardial infarction (MI), stroke, hospitalization for heart failure (HF), and a combined outcome (MI, stroke, all-cause mortality).
  
  
  
  In the DPP-4 inhibitor vs SU comparison, there were 30 130 DPP-4 inhibitor initiators and 68 382 SU initiators. Their mean age was 75 years, 41% were men and 55% had a baseline CV condition. The HR for the composite outcome was 0.75 (95% CI 0.72-0.79) over a median treatment duration of 1 year, but the 1-year risks of MI were 1.00 (95% CI 0.89-1.12) and 1.47 (95% CI 1.38-1.56) per 100 patients for DPP-4 inhibitors and SUs, respectively, and the corresponding stroke risks were 0.98 (95% CI 0.87-1.10) and 1.09 (95% CI 1.01-1.17). For the DPP-4 inhibitor vs TZD comparison, there were 20 596 DPP-4 inhibitor initiators and 13 526 TZD initiators without previous HF. Their mean age was 74 years, 42% were men and 30% had a baseline CV event. The composite outcome HR was 0.94 (95% CI 0.86-1.02) over a median treatment duration of 1 year. The 1-year risk for MI was ~0.90 and for stroke it was ~0.80 per 100 patients in both DPP-4 inhibitor and TZD initiators.
  
  
  
  Although limited by the short treatment period, the present study suggests there is no increased short-term risk of MI, stroke or HF with DPP-4 inhibitors vs SUs/TZDs.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Real World Evidence, GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Mugdha
authors.identifier: 0000-0003-0223-1016
authors.initials: M
authors.lastname: Gokhale
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Michele
authors.initials: M
authors.lastname: Jonsson Funk
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lund
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pate
authors.affiliation: Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Simpson
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Til
authors.initials: T
authors.lastname: Stürmer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D006278:Medicare; D009026:Mortality; D016016:Proportional Hazards Models; D012306:Risk; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones
keywords: DPP-4 inhibitor; antidiabetic drug; database research; incretins; observational study; pharmaco-epidemiology