Baseline Sodium-Glucose Cotransporter-2 Inhibitor Use Strongly Attenuates the Uric Acid-Elevating Effect of Thiazide Exposure


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DOI:

https://doi.org/10.58600/eurjther1889

Keywords:

Sodium glucose cotransporter 2 inhibitors, hypertension, uric acid, thiazides

Abstract

Objective: Thiazide diuretics are among the major anti-hypertensive medications. However, their hyperuricemic effect restricts their use in patients with gout. Sodium glucose co-transporter 2 inhibitor (SGLT-2i) initiation lowers serum uric acid (SUA) levels. It is not known whether existing SGLT-2i use affects the SUA increasing effect of thiazides.

Methods: Post-hoc data analysis of our published study was conducted. Hypertensive patients who were initiated on thiazide diuretics or whose dose escalated were included (thiazide exposure). Demographic, clinical, and laboratory data were acquired via an electronic database. Patients were grouped according to SGLT-2i presence at the time of thiazide exposure. Since the number of SGLT-2i users was low, bootstrapping via simple random sampling was performed.

Results: 144 patients were included in the study, of whom 13 were on SGLT-2i. Initial sample analysis revealed that while baseline SUA levels were similar between groups, SUA change was significantly lower after thiazide exposure among patients receiving SGLT-2i (0.6 vs. 0.2, p = 0.039). Similarly, baseline SUA levels were similar, but SUA change after thiazide exposure was significantly lower among patients receiving SGLT-2 on bootstrapped data (0.13 [-0.25 - 0.57, 95%CI], vs. 0.61 [0.45 - 0.78, 95%CI], mean difference = 0.48, [0.04 - 0.91, 95%CI], p = 0.029).

Conclusion: This study revealed that thiazide diuretics may be a safe anti-hypertensive medication in terms of hyperuricemia among patients using SGLT-2i. Further studies with similar outcomes may result in the elimination of restrictive recommendations for the use of thiazides in patients with hyperuricemia or gout, provided patients are on SGLT-2i.

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References

Ostchega Y, Fryar CD, Nwankwo T, Nguyen DT. (2020) Hypertension Prevalence Among Adults Aged 18 and Over: United States, 2017-2018. NCHS Data Brief. (364):1-8.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 285(19):2486-2497. https://doi.org/10.1001/jama.285.19.2486

Grundy SM. (2007 )Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab. 92(2):399-404. https://doi.org/10.1210/jc.2006-0513

Borghi C, Agabiti-Rosei E, Johnson RJ, et al. (2020) Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med. 80:1-11. https://doi.org/10.1016/j.ejim.2020.07.006

Zhu Y, Pandya BJ, Choi HK. (2012) Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am J Med. 125(7):679-687.e1. https://doi.org/10.1016/j.amjmed.2011.09.033

Choi HK, Ford ES, Li C, Curhan G. (2007) Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 57(1):109-115. https://doi.org/10.1002/art.22466

Copur S, Demiray A, Kanbay M. (2022) Uric acid in metabolic syndrome: Does uric acid have a definitive role?. Eur J Intern Med. 103:4-12. https://doi.org/10.1016/j.ejim.2022.04.022

Borghi C, Agabiti-Rosei E, Johnson RJ, et al. (2020) Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med. 80:1-11. https://doi.org/10.1016/j.ejim.2020.07.006

Thomas MC, Jandeleit-Dahm K, Bonnet F. (2014) Beyond Glycosuria: Exploring the intrarenal effects of SGLT₋2 inhibition in diabetes. Diabetes Metab. 40(6 Suppl 1):S17-S22. https://doi.org/10.1016/S1262-3636(14)72691-6

Yamada T, Wakabayashi M, Bhalla A, et al. (2021) Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis. Cardiovasc Diabetol. 20(1):14. https://doi.org/10.1186/s12933-020-01197-z

Hussain M, Elahi A, Hussain A, Iqbal J, Akhtar L, Majid A. (2021) Sodium-Glucose Cotransporter-2 (SGLT-2) Attenuates Serum Uric Acid (SUA) Level in Patients with Type 2 Diabetes. J Diabetes Res. 2021:9973862. https://doi.org/10.1155/2021/9973862

Langford HG, Blaufox MD, Borhani NO, et al. (1987) Is thiazide-produced uric acid elevation harmful? Analysis of data from the Hypertension Detection and Follow-up Program. Arch Intern Med. 147(4):645-649. https://doi.org/10.1001/archinte.147.4.645

Lee JS, Kwon OC, Oh JS, et al. (2020) Clinical features and recurrent attack in gout patients according to serum urate levels during an acute attack. Korean J Intern Med. 35(1):240-248. https://doi.org/10.3904/kjim.2018.205

Williams B, Mancia G, Spiering W, et al. (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension [published correction appears in Eur Heart J. 2019 Feb 1;40(5):475]. Eur Heart J. 39(33):3021-3104. https://doi.org/10.1093/eurheartj/ehy339

Whelton PK, Carey RM, Aronow WS, et al. (2018) 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Hypertension. 2018 Jun;71(6):e140-e144]. Hypertension. 71(6):e13-e115. https://doi.org/10.1161/HYP.0000000000000065

Mancia Chairperson G, Kreutz Co-Chair R, Brunström M, et al. (2023) 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension Endorsed by the European Renal Association (ERA) and the International Society of Hypertension (ISH) [published online ahead of print, 2023 Jun 21]. J Hypertens. 10.1097/HJH.0000000000003480. https://doi.org/10.1097/HJH.0000000000003480

Struthers A, Krum H, Williams GH. (2008) A comparison of the aldosterone-blocking agents eplerenone and spironolactone. Clin Cardiol. 31(4):153-158. https://doi.org/10.1002/clc.20324

Mansbart F, Kienberger G, Sönnichsen A, Mann E. (2022) Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing. BMC Geriatr. 22(1):771. https://doi.org/10.1186/s12877-022-03415-7

Güven AT, Özdede M, Şener YZ, et al. (2023) Evaluation of machine learning algorithms for renin-angiotensin-aldosterone system inhibitors associated renal adverse event prediction. Eur J Intern Med. 114:74-83. https://doi.org/10.1016/j.ejim.2023.05.021

Sanchez-Lozada LG, Rodriguez-Iturbe B, Kelley EE, et al. (2020) Uric Acid and Hypertension: An Update With Recommendations [published correction appears in Am J Hypertens. 2020 Dec 31;33(12):1150]. Am J Hypertens. 33(7):583-594. https://doi.org/10.1093/ajh/hpaa044

Singh JA, Reddy SG, Kundukulam J. (2011) Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol. 23(2):192-202. https://doi.org/10.1097/BOR.0b013e3283438e13

Chino Y, Samukawa Y, Sakai S, et al. (2014) SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm Drug Dispos. 35(7):391-404. https://doi.org/10.1002/bdd.1909

La Grotta R, de Candia P, Olivieri F, et al. (2022) Anti-inflammatory effect of SGLT-2 inhibitors via uric acid and insulin. Cell Mol Life Sci. 79(5):273. https://doi.org/10.1007/s00018-022-04289-z

Xin Y, Guo Y, Li Y, Ma Y, Li L, Jiang H. (2019) Effects of sodium glucose cotransporter-2 inhibitors on serum uric acid in type 2 diabetes mellitus: A systematic review with an indirect comparison meta-analysis. Saudi J Biol Sci. 26(2):421-426. https://doi.org/10.1016/j.sjbs.2018.11.013

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Published

2023-11-07

How to Cite

Güven, A. T., Özdede, M., & Şener, Y. Z. (2023). Baseline Sodium-Glucose Cotransporter-2 Inhibitor Use Strongly Attenuates the Uric Acid-Elevating Effect of Thiazide Exposure. European Journal of Therapeutics, 29(4), 741–747. https://doi.org/10.58600/eurjther1889

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