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Long-term and regular use of PPIs in treating acid-related diseases can lead to the onset of T2DM, particularly in younger patients with higher clinical severity, according to a recent case-control study. Therefore, physicians are advised to refrain from the unnecessary or long-term prescription of PPIs.

Proton pump inhibitors (PPIs) suppress the meal-stimulated and basal secretion of acid by irreversibly inhibiting H+/K+ ATPase located on the gastric parietal cells. PPIs are used in acid-related conditions, including Barett esophagus, peptic ulcers, gastrointestinal bleeding, and gastroesophageal reflux disease. Increased misuse of PPIs has led to various potential adverse outcomes. One of the clinically significant complications is the alteration of the gut microbiome, which leads to the development of metabolic disorders, including diabetes. There is limited evidence to support the association between prolonged administration of PPIs and the development of type 2 diabetes mellitus (T2DM). This case-control study, published in The Journal of Clinical Endocrinology and Metabolism, investigated the relationship between the long-term use of PPIs and the development of T2DM.
The study recruited 50,535 participants with diabetes, with an equal number as controls. The participants were matched for their clinical status, age, and sex. The investigators assessed exposure to treatment with PPIs in case-control pairs. Compared to those who consumed PPIs for a duration of < 8 weeks, greater odds of diabetes were observed in those who used PPIs for 8 weeks to 6 months, 6 months to 2 years, and greater than 2 years. Higher odds ratios of T2DM were observed in patients who were younger (40-65 years) and with worse clinical complexity. This association was found to be robust and consistent in the sensitivity analyses. In summary, the population-based case-control study demonstrates an increased risk of T2DM with prolonged PPI treatment, mainly in younger patients with higher clinical complexity. Therefore, physicians should refrain from the unnecessary prescription of PPIs, particularly for long-term use of this class of drugs. Reference Ciardullo, S., Rea, F., Savaré, L., Morabito, G., Perseghin, G., & Corrao, G. (2022). Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study. Journal of Clinical Endocrinology and Metabolism, 107(7), e2671-e2679. https://doi.org/10.1210/clinem/dgac231

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