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Chronic PPI Use Increases Risk of Type 2 Diabetes


Yuan J, He Q, Nguyen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2020 Sep 28:gutjnl-2020-322557. doi: 10.1136/gutjnl-2020-322557. Epub ahead of print. PMID: 32989021 

Study Summary

This prospective study of 200,000+ participants without type 2 diabetes from the Nurses' Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS) looked to determine the influence of chronic proton pump inhibitor (PPI) use on the development of type 2 diabetes.10,105 new cases of diabetes developed over 2,127,471 person-years of follow-up. For those who used PPIs for 0–2 years, the adjusted hazards ratio = 1.05 (95% CI 0.93 to 1.19 – a non-significant difference), but for those who used PPIs for more than 2 years, the aHR = 1.26 (95% CI 1.18 to 1.35). When combined, the overall risk of type 2 diabetes mellitus from regular PPI use was aHR = (HR 1.24, 95% CI 1.17 to 1.31), showing the risk of diabetes increased with duration of PPI use. 


Chronic use of PPIs increases the risk of type 2 diabetes, especially with use over 2 years. This finding adds to the list of adverse outcomes from PPIs. Other findings based upon cohort studies found chronic PPI use increased risk of hip fracture, atrophic gastritis, Clostridium difficile diarrhea, pneumonia, dementia, and rarely, chronic kidney disease. 

Stats Refresher

Confidence Intervals: the aHR for under 2 years of chronic PPI use was 1.05 but was found non-significant because the 95% confidence interval (CI) was 0.93-1.19; it crossed the number 1.0, meaning there was no significant difference between chronic PPI use and nonuse. Confidence intervals are significant when they are both less than 1.0 or both greater than 1.0. 

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