PMID- 27061884
OWN - NLM
STAT- MEDLINE
DCOM- 20170915
LR  - 20190318
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 38
IP  - 6
DP  - 2016 Jun
TI  - Safety of Concomitant Metformin and Proton Pump Inhibitor Use: A Population 
      Retrospective Cohort Study.
PG  - 1392-1400
LID - S0149-2918(16)30161-8 [pii]
LID - 10.1016/j.clinthera.2016.03.024 [doi]
AB  - PURPOSE: The purpose of this study was to investigate the effect of concomitant 
      use on important clinical outcomes. METHODS: In this retrospective cohort study, 
      a cohort of new metformin users was identified between 2004 and 2010 and followed 
      up until termination of insurance coverage, December 31, 2010, or the outcomes 
      were reached. The primary outcome was a composite of time to all-cause mortality 
      or hospitalization; our secondary outcome was time to cardiovascular 
      hospitalization. Exposures to metformin, a proton pump inhibitor (PPI), and/or a 
      histamine2 receptor antagonist (H2RA) were compared with a Cox proportional 
      hazards model after adjustment. FINDINGS: Relative to metformin-only users, 
      metformin and PPI users were at increased risk of the primary outcome (adjusted 
      hazard ratio [HR] = 1.55; 95% CI, 1.46-1.64); metformin and H2RA users also had 
      an elevated risk (adjusted HR = 1.29; 95% CI, 0.97-1.70). Similar patterns were 
      seen with cardiovascular-specific hospitalization. Compared with no drug use, 
      metformin users had an increased risk of the primary outcome, but risk was 
      substantially elevated when patients were taking PPIs or H2RAs, alone or in 
      combination with metformin. IMPLICATIONS: Concomitant use of metformin and a PPI 
      or metformin and an H2RA were associated with an increased risk of death or 
      hospitalization. This finding suggests that the harm observed may not be due to a 
      specific drug interaction but uncontrolled confounding secondary to an increased 
      risk in those patients using a PPI or H2RA.
CI  - Copyright (c) 2016 Elsevier HS Journals, Inc. All rights reserved.
FAU - Chen, Christopher B
AU  - Chen CB
AD  - School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
FAU - Lin, Mu
AU  - Lin M
AD  - School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
FAU - Eurich, Dean T
AU  - Eurich DT
AD  - School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
FAU - Johnson, Jeffrey A
AU  - Johnson JA
AD  - School of Public Health, University of Alberta, Edmonton, Alberta, Canada. 
      Electronic address: jeff.johnson@ualberta.ca.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
DEP - 20160406
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Histamine H2 Antagonists)
RN  - 0 (Proton Pump Inhibitors)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Drug Therapy, Combination
MH  - Female
MH  - Histamine H2 Antagonists/*adverse effects
MH  - Hospitalization
MH  - Humans
MH  - Male
MH  - Metformin/*adverse effects
MH  - Middle Aged
MH  - Proportional Hazards Models
MH  - Proton Pump Inhibitors/*adverse effects
MH  - Retrospective Studies
OTO - NOTNLM
OT  - *Death
OT  - *Hospitalization
OT  - *Metformin
OT  - *Proton Pump Inhibitors
EDAT- 2016/04/12 06:00
MHDA- 2017/09/16 06:00
CRDT- 2016/04/11 06:00
PHST- 2016/01/19 00:00 [received]
PHST- 2016/03/04 00:00 [revised]
PHST- 2016/03/14 00:00 [accepted]
PHST- 2016/04/11 06:00 [entrez]
PHST- 2016/04/12 06:00 [pubmed]
PHST- 2017/09/16 06:00 [medline]
AID - S0149-2918(16)30161-8 [pii]
AID - 10.1016/j.clinthera.2016.03.024 [doi]
PST - ppublish
SO  - Clin Ther. 2016 Jun;38(6):1392-1400. doi: 10.1016/j.clinthera.2016.03.024. Epub 
      2016 Apr 6.