Does PPI Use Affect Risk of Developing Diabetes?


Regular use of proton pump inhibitors could increase the risk of developing diabetes, but the findings are based off an observational study.


Regular use of proton pump inhibitors (PPIs), commonly-prescribed agents for acid reflux, may be associated with an increased risk of type 2 diabetes, according to a study published in Gut.

A prospective analysis of approximately 200,000 participants analyzed the risk of PPIs in long-term users, evaluating hazard ratios that adjusted for potentially influential factors such as demographics, lifestyle habits, comorbidities, use of other medications, and clinical indications.

The study investigators noted that the study was observational, and as such, can’t establish cause. However, the analysis included many individuals whose health was tracked over a relatively long period of time.

Investigators used data of the participants, none of whom had diabetes at the start of the study, from the Nurses’ Health Study (NHS), NHS II, and Health Professionals Follow-up Study (HPFS). At enrollment and for every 2 years after that, participants updated information on their health behaviors, medical history, and newly diagnosed conditions. Over the course of follow-up, the investigators documented 10,105 incident cases of diabetes over 2,127,471 person-years.

Overall, regular PPI users demonstrated a 24% higher risk of developing diabetes compared with non-users (HR 1.24, 95% CI 1.17 to 1.31), according to the findings. The risk of diabetes appeared to increase along with the duration of PPI use, the investigators noted, with use for up to 2 years associated with a 5% increased risk and use for more than 2 years associated with a 26% increased risk.

Additionally, further analysis showed that the risk of diabetes among PPI users was not affected by sex, age, family history of diabetes, smoking, alcohol intake, diet, physical activity, high cholesterol or regular use of anti-inflammatory drugs. However, the risk was still higher among participants who weren’t overweight or who had normal blood pressure.

“Given the range of side effects and the heightened risk of diabetes, doctors should carefully weigh up the pros and cons of prescribing these drugs,” the investigators wrote. “For patients who have to receive long-term PPI treatment, screening for abnormal blood glucose and type 2 diabetes is recommended.”


Yuan J, He Q, Nyugen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2020. doi: 10.1136/gutjnl-2020-322557

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