The Role of CYP8B1 Polymorphisms in Modulating the Biochemical Pathways Affected by SGLT2 Inhibitors in T2DM and Obesity

Summary

This study explores the long-term effects of dapagliflozin and empagliflozin on CYP8B1 gene expression and a range of metabolic, oxidative, and inflammatory biomarkers in obese patients with Type 2 Diabetes Mellitus (T2DM). Over a 6-month period, participants are assigned to three treatment arms: metformin (control), dapagliflozin, and empagliflozin. The study aims to determine how these medications influence bile acid metabolism, oxidative stress, leptin, GLP-1, IL-10, and IFN-γ, providing insight into the broader metabolic benefits of SGLT2 inhibitors

Timeline

Start

2025-07-15

Primary completion

2025-08-30

Completion

2026-03-15

Publications

• Results Scheen AJ. Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020 Oct;16(10):556-577. doi: 10.1038/s41574-020-0392-2. Epub 2020 Aug 27.
• Results Malone JI, Hansen BC. Does obesity cause type 2 diabetes mellitus (T2DM)? Or is it the opposite? Pediatr Diabetes. 2019 Feb;20(1):5-9. doi: 10.1111/pedi.12787. Epub 2018 Nov 5.
• Results Klen J, Dolzan V. Treatment Response to SGLT2 Inhibitors: From Clinical Characteristics to Genetic Variations. Int J Mol Sci. 2021 Sep 10;22(18):9800. doi: 10.3390/ijms22189800.
• Results Hegyi P, Maleth J, Walters JR, Hofmann AF, Keely SJ. Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease. Physiol Rev. 2018 Oct 1;98(4):1983-2023. doi: 10.1152/physrev.00054.2017.
• Results Fioretto P, Zambon A, Rossato M, Busetto L, Vettor R. SGLT2 Inhibitors and the Diabetic Kidney. Diabetes Care. 2016 Aug;39 Suppl 2:S165-71. doi: 10.2337/dcS15-3006.
• Results Chiang JYL, Ferrell JM. Bile Acids as Metabolic Regulators and Nutrient Sensors. Annu Rev Nutr. 2019 Aug 21;39:175-200. doi: 10.1146/annurev-nutr-082018-124344. Epub 2019 Apr 24.
• Results Chiang JY. Bile acid metabolism and signaling. Compr Physiol. 2013 Jul;3(3):1191-212. doi: 10.1002/cphy.c120023.
• Results Sarafidis PA, Tsapas A. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016 Mar 17;374(11):1092. doi: 10.1056/NEJMc1600827. No abstract available.

Drugs

Indications