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Clinical Summary

Proton Pump Inhibitors Raise the Risk of CVD and Mortality in T2D


  • In patients with type 2 diabetes (T2D), proton pump inhibitor use was associated with an increased risk of cardiovascular disease (CVD), such as coronary artery disease, myocardial infarction and heart failure, and all-cause mortality.
  • There was no significant association between the proton pump inhibitor use and stroke risk.

Why This Matters

  • Findings suggest that clinicians should consider benefit-risk assessments before prescribing proton pump inhibitors to patients with T2D.

Study Design

  • This was a large prospective cohort study that included 19,229 patients (age, 37-73 years) with T2D from the UK Biobank (2006-2010).
  • Primary outcomes: coronary artery disease, myocardial infarction, stroke, and heart failure.
  • Secondary outcome: all-cause mortality.
  • Funding: None disclosed.

Key Results

  • During a median follow-up of 10.9-11.2 years, 2971 cases of coronary artery disease, 1827 cases of myocardial infarction, 1192 cases of heart failure, 738 cases of stroke and 2297 deaths were reported.
  • Proton pump inhibitor users vs non-users had higher risks of (adjusted HR [aHR]; 95% CI):
    • coronary artery disease (1.27; 1.15 to 1.40);
    • myocardial infarction (1.34; 1.18 to 1.52);
    • heart failure (1.35; 1.16 to 1.57); and
    • all-cause mortality (1.30; 1.16 to 1.45).
  • No significant association was seen between proton pump inhibitor use and stroke risk (aHR 1.11; 95% CI 0.90 to 1.36).
  • These results were consistent in the subgroup analyses stratified by indications for proton pump inhibitors, anti-diabetic medication use and antiplatelet drug use.


  • Observational design.
  • Data on proton pump inhibitor use were self-reported.