Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study

Abstract

Context It is still debated whether prolonged use of proton pump inhibitors (PPIs) might affect metabolic health. Objective To investigate the relationship between prolonged use of PPIs and the risk of developing diabetes. Methods We performed a case-control study nested into a cohort of 777,420 patients newly treated with PPIs between 2010 and 2015 in Lombardy, Italy. A total of 50,535 cases diagnosed with diabetes until 2020 were matched with an equal number of controls that were randomly selected from the cohort members according to age, sex, and clinical status. Exposure to treatment with PPIs was assessed in case-control pairs based on time of therapy. A conditional logistic regression model was fitted to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the exposure-outcome association, after adjusting for several covariates. Sensitivity analyses were performed to evaluate the robustness of our findings. Results Compared to patients who used PPIs for <8 weeks, higher odds of diabetes of 19% (95% CI, 15–24%), 43% (38–49%), and 56% (49–64%) were observed among those who used PPIs for between 8 weeks and 6 months, 6 months and 2 years, and >2 years, respectively. The results were consistent when analyses were stratified according to age, sex and clinical profile, with higher ORs being found in younger patients and those with worse clinical complexity. Sensitivity analyses revealed that the association was consistent and robust. Conclusions Regular and prolonged use of PPIs is associated with a higher risk of diabetes. Physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use.

Alterations in gut microbiota and bile acids by proton‐pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance

“…Consistent with our results, a recent study of 9531 individuals found that PPI use was associated with increased serum levels of fasting insulin and insulin resistance 11 . In addition, several recent large population‐based cohort studies and case‐control studies have reported an increased risk of incident diabetes among PPI users 11–15 . Possible explanations for the conflicting results may include the differences in study populations (e.g., general individuals vs. diabetic patients), variations in the definition of PPI use, and the presence of confounding factors.…”

“…Our findings indicated that the gut microbiota-bile axis might partially mediate the relationships of PPI use with elevated FBG levels and IR, which provides mechanistic insight into the observed epidemiological association of PPI use and incident diabetes in previous studies. [11][12][13][14][15] The study population was restricted to patients with GERD, which eliminated the influence of clinical indications for PPI use. However, our study has several limitations.…”

“…Accumulating observational studies found that PPI use was associated with metabolic diseases, like obesity, diabetes, metabolic syndrome, and fatty liver disease 6–10 . Evidence from five recent large population‐based cohort studies and case–control studies reported that PPI users had a higher risk of diabetes 11–15 …”

From contact coverage to effective coverage of community care for patients with severe mental disorders: A real-world investigation from Italy

“…In Italy, all citizens have equal access to healthcare provided by the National Health Service (NHS). An automated system of HCU databases is used to locally manage health services in each region ( 16 ). HCU data include a variety of information on residents, such as diagnosis at discharge from public or private hospitals, outpatient drug prescriptions, specialist visits and diagnostic exams provided fully or partly free-of-charge by the NHS.…”

“Chronic Exposure to Proton Pump Inhibitor use and Diabetes Mellitus Incidence. A Systemic Review and Meta-Analysis “

“…].A case-control study by HY et al, from Taiwan's National Health Insurance Research Database between 1998 and 2013 with a total of 20,940 patients with T2DM and 20,940 controls have shown that, Compared with the cumulative de ned daily dose (cDDD) ≤ 30 mg, higher dosage of PPI exposure was associated with an increased risk of T2DM development: cDDD 31-120 (odds ratio [OR]: 1.20, 95% con dence interval [CI]: 1.13-1.26). Dose-dependent increased risk of T2DM was found among patients with higher doses of PPIs compared with those with lower doses of PPIs[14].in the subgroup analysis of individual PPIs and incidence of diabetes risk showed that pantoprazole (OR: 1.14, 95% CI: 1.07-1.21), lansoprazole (OR: 1.08, 95% CI: 1.03-1.12), and omeprazole (OR: 1.11, 95% CI: 1.06-1.16) have shown a signi cantly high association than rabeprazole, esomeprazole.In another large, nested case-control study by Ciardullo S et al, in a cohort of 777,420 patients, a total of 50,535 cases diagnosed with diabetes until 2020 were matched with an equal number of controls that were randomly selected from the cohort members according to age, sex, and clinical status have shown that, compared with patients who received PPIs for less than 8 weeks, patients who have received PPIs for 8 weeks to 6 months had a 19% of increased risk, Patients who have received PPIs for 6 months to 2 years had a 43% increased risk of the outcome, and those who received PPIs for more than 2 years had a 56% increased risk of the outcome of being diagnosed with diabetes during follow-up, after adjusting for age, clinical pro le, comorbidities, medical therapy, and PPI type[15]. who are on higher PPI dosage were with signi cantly increased risk) in those on more than one de ned daily dose (HR 1.88, 95% CI;1.29-2.75) and a longer duration of PPI use increases the incidence of diabetes[17].…”