Authors’ reply
We would like to thank Patoulias and colleagues for their observations, highlighting a possible association between proton pump inhibitors (PPIs) use and diabetes mellitus (DM). Besides the meta-analysis by Yuan et al,1 including 3 cohorts of health professionals showing that regular PPIs use was likely to be associated with an increased risk of type 2 DM compared with controls, the evidence on such association appears contradictory and inconclusive to date.
Although similar changes in the microbiota phenotype have been reported between PPI users and patients affected by DM, suggesting that gut microbiota may mediate this association, the exact mechanisms have not yet been clarified. On the contrary, it has been suggested that PPIs could be effective as antidiabetic agents, since they increase serum gastrin concentrations, whereby affecting glucose metabolism through promoting β-cell regeneration and also enhancing insulin secretion.2,3 Indeed, a meta-analysis on this topic found no significant effect on glucose metabolism and insulin resistance in patients with type 2 DM treated with PPIs4 and population-based cohort studies demonstrated a decreased risk of DM in patients with upper gastrointestinal disease taking PPIs.5
Nevertheless, we agree with Patoulias and colleagues that clinicians should prescribe PPIs with caution to those affected by DM, as they represent patients at a high risk for developing cardiovascular complications and, as reported in our review, long-term PPIs use is associated with an increased risk of cardiovascular events.6 Therefore, we also agree that further research is warranted to investigate the association, if any, between PPIs and DM, to clarify possible underlying mechanisms and their clinical implications.
Chiara Castellana, Andrea Telese, Leonardo H. Eusebi (CC and HE: Gastroenterology and Endoscopy Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; AT: Department of Gastroenterology, University College London Hospital [UCLH], London, United Kingdom)
None declared.
Castellana C, Telese A, Eusebi LH. Proton pump inhibitors and the development of diabetes and its complications: a risk hidden in the shadows? Authors’ reply. Pol Arch Intern Med. 2021; 131: 591. doi:10.20452/pamw.16043
- 1.
- Yuan J, He Q, Nguyen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2021; 70: 1070-1077.Crossref
- 2.
- Boj-Carceller D. Proton pump inhibitors: impact on glucose metabolism. Endocrine. 2013; 43: 22-32.Crossref
- 3.
- Inci F, Atmaca M, Ozturk M, et al. Pantoprazole may improve beta cell function and diabetes mellitus. J Endocrinol Invest. 2014; 37: 449-454.Crossref
- 4.
- Sánchez-García A, Simental-Mendía M, Simental-Mendía LE. Effect of proton-pump inhibitors on glucose and insulin metabolism on patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Curr Pharm Des. 2020; 26: 4007-4013.Crossref
- 5.
- Lin HC, Hsiao YT, et al. The use of proton pump inhibitors decreases the risk of diabetes mellitus in patients with upper gastrointestinal disease: a population-based retrospective cohort study. Medicine (Baltimore). 2016; 95: e4195.Crossref
- 6.
- Castellana C, Pecere S, Furnari M, et al. Side effects of long-term use of proton pump inhibitors: practical considerations. Pol Arch Intern Med. 2021; 131: 541-549.Crossref