Disclosures: The authors report no relevant financial disclosures.
October 06, 2020
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Regular use of proton pump inhibitors may increase type 2 diabetes risk

Disclosures: The authors report no relevant financial disclosures.
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The risk for developing type 2 diabetes rose with regular use of proton pump inhibitors, particularly for longer than 2 years, but the risk decreased when the drugs were discontinued, according to study results published in Gut.

“Regular proton pump inhibitor use was likely to be associated with an increased risk of type 2 diabetes, particularly for those with prolonged use,” Jinqiu Yuan, PhD, of The Seventh Affiliated Hospital, Sun Yat-sen University in Shenzhen, China, and colleagues wrote. “Owing to its wide usage, the overall number of diabetes cases associated with proton pump inhibitor use could be considerable.”

Individuals who regularly used protein pump inhibitors were at greater risk for developing type 2 diabetes, with the risk decreasing after use was discontinued.

Researchers conducted a prospective analysis of 204,689 participants in the Nurses’ Health Study (NHS), NHS II and Health Professionals Follow-Up Study who used proton pump inhibitors (PPIs) and did not have diabetes at baseline. Every 2 years after baseline, participants reported whether they used PPIs regularly during the previous 2 years. Regular use of PPI was defined as using two times or more per week. Participants also reported whether they had ever received a diagnosis of diabetes, which researchers confirmed with a subsequent questionnaire. Researchers used 2000 as the baseline for NHS and continued follow-up through 2014; 2001 was baseline for NHS II with follow-up through 2017, and 2004 was baseline in the Health Professionals Follow-Up Study with follow-up through 2016.

In pooled data, 13,528 participants said they used PPI regularly. During 2,127,471 person-years of follow-up, there were 10,105 diabetes diagnoses, with more cases in the regular PPI user group (7.44 per 1,000 person-years) vs. the nonuser group (4.32 per 1,000 person-years). After adjusting for demographic factors, lifestyle habits, comorbidities, other medications and clinical indications for PPI use, the PPI user group had a higher risk for type 2 diabetes compared with nonusers (HR = 1.24; 95% CI, 1.17-1.31).

The risk for diabetes increased the longer individuals stayed on PPI. When compared with nonusers, those who used PPI for 2 years or less were at a slightly elevated risk for diabetes (HR = 1.05; 95% CI, 0.93-1.19), whereas those who used PPI for more than 2 years were at a higher risk (HR = 1.26; 95% CI, 1.18-1.35). Those in the user group who stopped using PPI within 2 years of starting (HR = 0.83; 95% CI, 0.7-0.98) or after more than 2 years of use (HR = 0.81; 95% CI, 0.76-0.86) were at a lower risk for diabetes than current PPI users.

“The mechanism underlying the association between PPI use and diabetes is still unclear,” the researchers wrote. “Increasing evidence suggests that gut microbiota may mediate this association. Previous studies have shown that PPI use is associated with reduced diversity of gut microbiome and consistent changes in the microbiota phenotype. ... Observational studies have also suggested that other medicines with a major impact on gut microbiota, such as antibiotics, are associated with an increased risk of diabetes. In addition, as mentioned previously, PPI use could result in weight gain, metabolic syndrome and chronic liver disease, which in turn may increase the risk of type 2 diabetes.”

More studies are needed to investigate the mechanisms and confirm the findings, but researchers added that providers should be aware of possible adverse effects in prescribing 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,” the researchers wrote. “For patients who have to receive long-term PPI treatment, screening for abnormal blood glucose and type 2 diabetes is recommended.”