Regular use of PPIs linked to increased risk of type 2 diabetes

In an analysis of the Nurses' Health and Health Professionals studies, regular users of proton-pump inhibitors (PPIs) had a 24% higher risk of diabetes than nonusers, with longer duration of use associated with greater risk.


Regular use of proton-pump inhibitors (PPIs) was associated with an increased risk of type 2 diabetes in a recent study.

Researchers conducted an analysis of 204,689 participants free of diabetes in three prospective cohorts: the Nurses' Health Study (NHS), the NHS II, and the Health Professionals Follow-up Study. They evaluated regular use of PPIs and risk of type 2 diabetes and adjusted hazard ratios (HRs) for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications, and clinical indications. Participants self-reported on biennial questionnaires whether they had ever been diagnosed with diabetes, and researchers confirmed diagnoses (using American Diabetes Association diagnostic criteria) by mailing a supplementary questionnaire to collect data on date of diagnosis, symptoms, diagnostic testing, and diabetes drug treatment. Results were published online on Sept. 28 by Gut.

This study included 176,050 women from the NHS (n=80,500) and NHS II (n=95,550) and 28,639 men from the Health Professionals Follow-up Study. At baseline, regular PPI users (n=13,528) tended to be less physically active, had higher rates of hypertension and hypercholesterolemia, and were more likely to use NSAIDs and steroids than non-PPI users (n=191,161). Overall, there were 10,105 incident cases of diabetes over 2.13 million person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than nonusers (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 up to two years and 1.26 (95% CI, 1.18 to 1.35) for participants who used PPIs for more than two years compared with nonusers. Stopping PPI use was likely to be associated with a lower risk of diabetes. Every 318.9 (95% CI, 285.2 to 385.0), 170.8 (95% CI, 209.7 to 150.8), and 77.3 (95% CI, 97.0 to 66.8) regular PPI users may result in one case of diabetes over one, two, and five years, respectively, the authors calculated. In subgroup analyses, the risk of diabetes with PPI use seemed to be higher among participants with lower body mass index or normal blood pressure (P<0.05 for interactions).

Limitations of the study include its observational design and the lack of detailed data on PPI use, including dosage, frequency, brand, and indications, the authors noted. They added that the association between PPI use and diabetes may be confounded by the indications for use of PPIs.

“Given the potential risk of diabetes and other adverse effects such as enteric infections, clinicians should carefully balance the benefits and harms in prescribing PPIs, particularly for long-term continuous use,” they concluded. “For patients who have to receive long-term PPI treatment, screening for abnormal blood glucose and type 2 diabetes is recommended.”