Long-term use of proton pump inhibitors and its impact on glucose homeostasis: results of a prospective observational study
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20251067Keywords:
PPIs, Dys-glycemia, ADRs of PPIsAbstract
Background: Proton pump inhibitors (PPIs) being the commonly used medications in various gastrointestinal diseases, and were so far considered as most tolerated and safe medications with few, mild adverse effects associated with their use, but of late there have some concerns emerged on their long-term use and the one important observation is their impact on glucose homeostasis. Aim of the study was to measure the dysglycemic potential of proton pump inhibitors by estimating blood sugar and HbA1c at baseline, 6 months and 1 year follow up in patients put on long-term PPIs.
Methods: 150 patients of both the sexes, aged ≥18 years and diagnosed as gastroesophageal reflux disease (GERD), functional dyspepsia or ulcer dyspepsia were included in the study. Patients excluded from the study were those who didn’t consent for their inclusion, known cases of diabetes, any liver or renal disease, pregnant ladies and the ones who were on medications like NSAIDs, steroids or any other hormone.
Results: Mean age of the studied subjects being 41.5±14.6 years with the male: female ratio of 1.1:1. The mean body mass index (BMI) of the patients was 24.5±2.7 kg/m2. Prevalence of hypertension and hypothyroidism and hypercholesterolemia among the participants was 36%, 34.7% and 36.7% respectively and 18% participants had family history of diabetes.
Conclusions: The conclusions that can be drawn from the presents study are that in patients undergoing long-term more than 12 weeks treatment with PPI, there is a significant increase in overall blood glucose parameters, as measured by fasting blood glucose, random blood glucose, and glycosylated haemoglobin.
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References
Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11(1):27. DOI: https://doi.org/10.5009/gnl15502
Nehra AK, Alexander JA, Loftus CG, Nehra V. Proton pump inhibitors: review of emerging concerns. Mayo Clin Proceed. 2018;93(2):240-6. DOI: https://doi.org/10.1016/j.mayocp.2017.10.022
Mössner J. The indications, applications, and risks of proton pump inhibitors: A review after 25 years. Deutsches Ärzteblatt Int. 2016;113(27-28):477. DOI: https://doi.org/10.3238/arztebl.2016.0477
Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Safety. 2019;2042098618809927. DOI: https://doi.org/10.1177/2042098618809927
Chen J, Yuan YC, Leontiadis GI, Howden CW. Recent safety concerns with proton pump inhibitors. J Clin Gastroenterol. 2012;46(2):93-114. DOI: https://doi.org/10.1097/MCG.0b013e3182333820
Chait MM. Gastroesophageal reflux disease: Important considerations for the older patients. World J Gastrointest Endosc. 2010;2(12):388-96. DOI: https://doi.org/10.4253/wjge.v2.i12.388
Maret-Ouda J, Markar SR, Lagergren J. Gastroesophageal reflux disease: a review. JAMA. 2020;324(24):2536-47. DOI: https://doi.org/10.1001/jama.2020.21360
Rajput MA, Ali F, Zehra T, Zafar S, Kumar G. The effect of proton pump inhibitors on glycaemic control in diabetic patients. J Taibah Univ Med Sci. 2020;15(3):218-23. DOI: https://doi.org/10.1016/j.jtumed.2020.03.003
He Q, Yang M, Qin X, Fan D, Yuan J, Pan Y. Risk stratification for proton pump inhibitor-associated type 2 diabetes: a population-based cohort study. Gut. 2021;70:2212-3. DOI: https://doi.org/10.1136/gutjnl-2020-323816
Abrahami D, McDonald EG, Schnitzer M, Azoulay L. Trends in acid suppressant drug prescriptions in primary care in the UK: a population-based cross-sectional study. BMJ Open. 2020;10(12):e041529. DOI: https://doi.org/10.1136/bmjopen-2020-041529
Hálfdánarson ÓÖ, Pottegård A, Björnsson ES, Lund SH, Ogmundsdottir MH, Steingrímsson E, et al. Proton-pump inhibitors among adults: a nationwide drug-utilization study. Ther Adv Gastroenterol. 2018;11:1756284818777943. DOI: https://doi.org/10.1177/1756284818777943
Hvid-Jensen F, Nielsen RB, Pedersen L, Funch-Jensen P, Drewes AM, Larsen FB, et al. Lifestyle factors among proton pump inhibitor users and nonusers: a cross-sectional study in a population-based setting. Clin Epidemiol. 2013;493-9. DOI: https://doi.org/10.2147/CLEP.S49354
Boj-Carceller D. Proton pump inhibitors: impact on glucose metabolism. Endocrine. 2013;43:22-32. DOI: https://doi.org/10.1007/s12020-012-9755-3
Hove KD, Brøns C, Færch K, Lund SS, Petersen JS, Karlsen AE, et al. Effects of 12 weeks’ treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomized double-blind prospective placebo-controlled study. Diabetologia. 2013;56:22-30. DOI: https://doi.org/10.1007/s00125-012-2714-y
Lin HC, Hsiao YT, Lin HL, Uang YS, Cheng HW, Wang Y, 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. 2016;95(28). DOI: https://doi.org/10.1097/MD.0000000000004195
Gómez-Izquierdo JC, Yu OH. The influence of proton-pump inhibitors on glycemic control: a systematic review of the literature and a meta-analysis. Canad J Diabet. 2017;41(4):351-61. DOI: https://doi.org/10.1016/j.jcjd.2016.11.004
Blume H, Donath F, Warnke A, Schug BS. Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Saf. 2006;29:769-84. DOI: https://doi.org/10.2165/00002018-200629090-00002
Thomson AB, Sauve MD, Kassam N, Kamitakahara H. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010;16(19):2323. DOI: https://doi.org/10.3748/wjg.v16.i19.2323
Ciardullo S, Rea F, Savaré L, Morabito G, Perseghin G, Corrao G. Prolonged use of proton pump inhibitors and risk of type 2 diabetes: results from a large population-based nested case-control study. J Clin Endocrinol Metab. 2022;107(7):e2671-9. DOI: https://doi.org/10.1210/clinem/dgac231
Yuan J, He Q, Nguyen LH, Wong MC, Huang J, Yu Y, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2021;70(6):1070-7. DOI: https://doi.org/10.1136/gutjnl-2020-322557
Czarniak P, Ahmadizar F, Hughes J, Parsons R, Kavousi M, Ikram M, et al. Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population‐based cohort study. Br J Clin Pharmacol. 2022;88(6):2718-26. DOI: https://doi.org/10.1111/bcp.15182
Kuo HY, Liang CS, Tsai SJ, Chen TJ, Chu CS, Chen MH. Dose-Dependent Proton Pump Inhibitor Exposure and Risk of Type 2 Diabetes: A Nationwide Nested Case–Control Study. Int J Env Res Public Health. 2022;19(14):8739. DOI: https://doi.org/10.3390/ijerph19148739
Guo YR, Liu XM, Wang GX. Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis. World J Diabetes. 2023;14(2):120. DOI: https://doi.org/10.4239/wjd.v14.i2.120
Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157(3):682-91. DOI: https://doi.org/10.1053/j.gastro.2019.05.056
Trang A, Bushman J, Halalau A. Effect of long-term proton pump inhibitor use on glycemic control in patients with type two diabetes mellitus. J Diabetes Res. 2021;2021:1-4. DOI: https://doi.org/10.1155/2021/5578265
Crouch MA, Mefford IN, Wade EU. Proton pump inhibitor therapy associated with lower glycosylated hemoglobin levels in type 2 diabetes. J Am Board Fam Med. 2012;25(1):50-4. DOI: https://doi.org/10.3122/jabfm.2012.01.100161
Naito Y, Kashiwagi K, Takagi T, Andoh A, Inoue R. Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use. Digestion. 2018;97(2):195-204. DOI: https://doi.org/10.1159/000481813
Villegas K, Meier JL, Long M, Lopez J, Swislocki A. The Effect of Proton Pump Inhibitors on Glycemic Control in Patients with Type 2 Diabetes. Metab Syndr Relat Disord. 2019;17(4):192-6. DOI: https://doi.org/10.1089/met.2018.0138
Peng CC, Tu YK, Lee GY, Chang RH, Huang Y, Bukhari K, et al. Effects of proton pump inhibitors on glycemic control and incident diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2021;106(11):3354-66. DOI: https://doi.org/10.1210/clinem/dgab353