title: Use of Dipeptidyl-Peptidase-4 Inhibitors and the Risk of Pneumonia: A Population-Based Cohort Study.
abstract: BACKGROUND
  Dipeptidyl-peptidase-4 inhibitors (DPP4Is) are drugs for the treatment of type 2 diabetes mellitus (T2DM). There is increasing evidence that DPP4Is may result in suppression of the immune system and may increase the risk of infections such as pneumonia. Aim of this study was to evaluate the association between the use of DPP4Is and the risk of pneumonia in a population-based study.
  
  
  METHODS
  We conducted a population-based cohort study using data from the world's largest primary care database, the UK Clinical Practice Research Datalink (CPRD). We selected all users of non-insulin antidiabetic drugs (NIADs), including DPP4Is, between 2007 and 2012. To each NIAD user, we matched randomly selected non-users. The NIAD user's first prescription defined the index date, which was then assigned to the matched non-users. Patients were followed from their first prescription until end of data collection or the first event of pneumonia, whichever came first. Cox regression analysis estimated the association between pneumonia and current use of DPP4Is versus 1) current use of other NIADs and 2) non-users. DPP4I use was then stratified to daily and cumulative dose. Analyses were statistically adjusted for age, sex, lifestyle factors and comorbidities and concomitant use of various other drugs.
  
  
  RESULTS
  Risk of pneumonia was not increased with current DPP4I use versus use of other NIADs, adjusted Hazard Ratio (HR) 0.70; 95% Confidence Interval (CI) 0.55-0.91. Also higher cumulative doses or daily doses did not further increase risk of pneumonia.
  
  
  CONCLUSIONS
  We found no increased risk of pneumonia in T2DM patients using DPP4Is compared to T2DM patients using other NIADs. Our finding is in line with direct and indirect evidence from observational studies and RCTs. There is probably no need to avoid prescribing of DPP4Is to elderly patients who are at risk of pneumonia.
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University, Medical Centre+, Maastricht, Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Wvan der Zanden
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University, Medical Centre+, Maastricht, Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Arief
authors.initials: A
authors.lastname: Lalmohamed
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University, Medical Centre+, Maastricht, Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Johanna H M
authors.initials: JH
authors.lastname: Driessen
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Department of Respiratory Medicine, Maastricht University, Medical Centre+, Maastricht, Netherlands.
authors.forename: Gernot
authors.initials: G
authors.lastname: Rohde
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University, Medical Centre+, Maastricht, Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Neef
authors.affiliation: Department of Sexual Health, Infectious Diseases and Environmental Health, Public Health Service South Limburg, Geleen, Netherlands; Department of Microbiology, Maastricht University Medical Centre+, Maastricht, Netherlands.
authors.forename: Casper
authors.initials: C
authors.lastname: den Heijer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced* / Q000453:epidemiology; D012306:Risk; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors