Prevention of biliary diseases associated with GLP-1 receptor agonist therapy
https://doi.org/10.51793/OS.2026.29.4.014
Abstract
Background. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1a) have emerged as pivotal therapeutic agents in the management of metabolic disorders, particularly type 2 diabetes mellitus and obesity. This is due to their ability to improve glycemic control and facilitate weight loss by enhancing insulin secretion, suppressing glucagon release and delaying gastric emptying by promoting prolonged satiety and reducing appetite. However, despite their clinical efficacy, therapy with GLP-1RAs has been associated with an increased risk of gallbladder disease, especially with prolonged use and higher doses.
Objective. The aim of this study is to evaluate current clinical data regarding the incidence and severity of adverse effects involving gallbladder and biliary tract in patients receiving GLP-1α therapy, to evaluate potential prevention strategies and to assess the efficacy of ursodeoxycholic acid (UDCA) in this patient population. The objective of this review is to examine the potential mechanisms through which GLP-1 receptor agonists may contribute to the development of biliary tract diseases. Recent systematic reviews, meta-analyses and Randomized Controlled Trials (RCTs) indicate an increased risk of gallbladder and biliary tract diseases with GLP-1 receptor agonist therapy. The risk is highest with high-dose and long-term therapy, as well as in patients treated for weight loss and type 2 diabetes mellitus (T2DM). The increased risk of gallbladder diseases associated with GLP-1 receptor agonists therapy has important clinical implications necessitating careful monitoring of the gallbladder and biliary tract before initiation, as well as of patients receiving GLP-1 receptor agonist therapy. UDCA positively affects choleresis, reduces the inflammation and improves metabolic parameters; therefore, it is recommended for the prevention and treatment of adverse events associated with GLP-1 receptor agonist therapy.
About the Author
Elena A. LjaljukovaRussian Federation
Elena A. Ljaljukova, Dr. of Sci. (Med.), Professor of the Department of Internal Medicine and Family Medicine of the Faculty of Additional Professional Education,
5, Petr Nekrasov str., Omsk, 644037.
References
1. He L., Li J., Cheng X., Luo L., Huang Y. Association between GLP-1 RAs and DPP-4 inhibitors with biliary disorders: pharmacovigilance analysis. Front Pharmacol. 2025; 16: 1509561. DOI: 10.3389/fphar.2025.1509561. PMID: 40041492; PMCID: PMC11878242.
2. Woronow D., Chamberlain C., Niak A., Avigan M., Houstoun M., Kortepeter C. Acute Cholecystitis Associated With the Use of Glucagon-Like Peptide-1 Receptor Agonists Reported to the US Food and Drug Administration. JAMA Intern Med. 2022; 182 (10): 1104-1106. DOI: 10.1001/jamainternmed.2022.3810. PMID: 36036939; PMCID: PMC9425280.
3. He L., Wang J., Ping F., Yang N., Huang J., Li Y., Xu L., Li W., Zhang H. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Metaanalysis of Randomized Clinical Trials. JAMA Intern Med. 2022; 182 (5): 513-519. DOI: 10.1001/jamainternmed.2022.0338. PMID: 35344001; PMCID: PMC8961394
4. Tao C., Zhang Y., Wan T., Zhao W., Chen J., Wang K., Yang L., Wang G., Ding Q., Shang J., Zhou M. Glucagon-like peptide-1 receptor agonist-induced cholecystitis and cholelithiasis: a real-world pharmacovigilance analysis using the FAERS database. Front Pharmacol. 2025; 16: 1557691. DOI: 10.3389/fphar.2025.1557691. PMID: 40697657; PMCID: PMC12279493.
5. Rehfeld J. F., Knop F. K., Asmar A., Madsbad S., Holst J. J., Asmar M. Cholecystokinin secretion is suppressed by glucagon-like peptide-1: clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs. Scand J Gastroenterol. 2018; 53 (12): 1429-1432. DOI: 10.1080/00365521.2018.1530297. Epub 2018 Nov 19. PMID: 30449207.
6. Physiology and Pharmacology of Effects of GLP-1-based Therapies on Gastric, Biliary and Intestinal Motility.Ryan J Jalleh and others. Endocrinology. 2025; 1 (166): 155. https:/doi.org/10.1210/endocr/bqae155.
7. Ilchenko A. A. Bile acids in normal and pathological conditions. Eksperimentalnaya i klinicheskaya gastroenterologiya (EiKG). 2010. №4. URL: https://cyberleninka.ru/article/n/zhelchnye-kisloty-v-norme-i-pripatologii (assessed: 05.06.2025). (In Russ.)
8. Kucheryavy Yu. A., Cheremushkin S. V. Therapeutic efficacy evaluation of the reference drug ursodeoxycholic acid and its analogues in the biliary sludge dissolution: a meta-analysis. Consilium Medicum. 2022; 24(12): 860-864. (In Russ.) DOI: 10.26442/20751753.2022.12.201429
9. Carotti S., Guarino M. P., Cicala M., Perrone G., Alloni R., Segreto F., Rabitti C., Morini S. Effect of ursodeoxycholic acid on inflammatory infiltrate in gallbladder muscle of cholesterol gallstone patients. Neurogastroenterol Motil. 2010; 22 (8): 866-873, e232. DOI: 10.1111/j.1365-2982.2010.01510.x. Epub 2010 Apr 20. PMID: 20426797.
10. Lakić B., Škrbić R., Uletilović S., MandićKovačević N., Grabež M., Šarić M. P., Stojiljković M. P., Soldatović I., Janjetović Z., Stokanović A., Stojaković N., Mikov M. Beneficial Effects of Ursodeoxycholic Acid on Metabolic Parameters and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind, PlaceboControlled Clinical Study. J Diabetes Res. 2024; 2024: 4187796. DOI: 10.1155/2024/4187796. PMID: 38455850; PMCID: PMC10919985.
11. Méndez-Sánchez N., González V., ChávezTapia N., Ramos M. H,, Uribe M. Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty liver disease. A double-blind, placebo-controlled trial. Ann Hepatol. 2004; 3 (3): 108-112.
12. Rashidbeygi E., Rasaei N., Amini M. R., Salavatizadeh M., Mohammadizadeh M., Hekmatdoost A. The effects of ursodeoxycholic acid on cardiometabolic risk factors: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2025; 25 (1): 125. DOI: 10.1186/s12872-025-04549-3. PMID: 39984850; PMCID: PMC11844182.
13. Winston J. A., Rivera A., Cai J., Patterson A. D., Theriot C. M. Secondary bile acid ursodeoxycholic acid alters weight, the gut microbiota, and the bile acid pool in conventional mice. PLoS ONE. 2021; 16 (2): e0246161.
14. Wahlström A., Kovatcheva-Datchary P., Ståhlman M., Bäckhed F., Marschall H.-U. Crosstalk between bile acids and gut microbiota and its impact on farnesoid X receptor signalling. Dig Dis. 2017; 35 (3): 246-250.
15. Fiorucci S., Distrutti E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med. 2015; 21 (11): 702-714.
16. Al-Salami H., Mamo J., Mooranian A., Negrulj R., Lam V., Elahy M., Takechi R. Long-term supplementation of microencapsulated ursodeoxycholic acid prevents hypertension in a mouse model of insulin resistance. Exp Clin Endocrinol Diabetes. 2017; 125 (01): 28-32.
17. Schiedermaier P., Hansen S., Asdonk D., Brensing K.-A., Sauerbruch T. Effects of ursodeoxycholic acid on splanchnic and systemic hemodynamics. Digestion. 2000; 61 (2): 107-112.
18. State Register of Medicines. http://www.grls.rosminzdrav.ru.
19. Clinical guidelines "Gallstone disease", Ministry of Health of the Russian Federation, 2024. (In Russ.)
Review
For citations:
Ljaljukova E.A. Prevention of biliary diseases associated with GLP-1 receptor agonist therapy. Lechaschi Vrach. 2026;(4):101-108. (In Russ.) https://doi.org/10.51793/OS.2026.29.4.014
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