Objective The association between the regular use of proton pump inhibitors (PPIs) and the risk of type 2 diabetes remains unclear, although a recent randomised controlled trial showed a trend towards increased risk. This study was undertaken to evaluate the regular use of PPIs and risk of type 2 diabetes.
Method This is a prospective analysis of 204 689 participants free of diabetes in the Nurses' Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS). Type 2 diabetes was confirmed using American Diabetes Association (ADA) diagnostic criteria. We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications and clinical indications.
Results We documented 10 105 incident cases of diabetes over 2 127 471 person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than non-users (HR 1.24, 95% CI 1.17 to 1.31). The risk of diabetes increased with duration of PPI use. Fully adjusted HRs were 1.05 (95% CI 0.93 to 1.19) for participants who used PPIs for >0–2 years and 1.26 (95% CI 1.18 to 1.35) for participants who used PPIs for >2 years compared with non-users.
Conclusions Regular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use. Physicians should therefore exercise caution when prescribing PPIs, particularly for long-term use.
- proton pump inhibition
- diabetes mellitus
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JY and QH are joint first authors.
Contributors JY had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: JY, CZ and YH. Acquisition, analysis or interpretation of data: All authors. Drafting of the manuscript: JY, QH and CZ. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: JY and QH. Obtained funding: JY and CZ. Administrative, technical or material support: YH and CZ. Supervision: YH and CZ.
Funding This work was supported by the Startup Fund for the 100 Top Talents Program, SYSU (392012), the National Heart, Lung, and Blood Institute grants (CA176726, CA186107, and CA167552) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants (DK082486, DK58845 and DK112940).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval This study was approved by the institutional review board at the Brigham and Women's Hospital.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party (firstname.lastname@example.org) and are not publicly available. Requests for access to data,questionnaires, and statistical code may be made by contacting the corresponding author at email@example.com.
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