Abstract
Background
Body weight reduction is the first-line recommendation in NAFLD patients. Dapagliflozin has a strong potential to reduce body weight in addition to its glycemic control effect
Objective
To study the effect of dapagliflozin on various parameters in NAFLD type 2 diabetic patients.
Methods
In this randomized controlled trial, 150 type 2 diabetic patients with NAFLD diagnosed on the basis of radiological findings and deranged liver enzymes were randomly allocated into two groups. Both groups were taking tab glimepiride as a standard treatment of type 2 diabetes. Group A was given tab dapagliflozin 5–10 mg while group B was given tab placebo in addition to lifestyle modifications for a period of 12 weeks. Body weight, BMI, HbA1c, and serum aminotransferases were analyzed pre- and post-treatment using SPSS 20.
Results
After 12 weeks of treatment, glycemic control was improved in both study groups, i.e., dapagliflozin (FBS from 95 ± 14 to 80 ± 11 mg/dl with p = 0.003, HbAIc from 7.5 ± 4.5 to 6.4 ± 5.4% with p = 0.002) and placebo (FBS from 100 ± 9.5 to 90.5 ± 13 mg/dl with p = 0.004, HbA1c from 8.2 ± 3.5 to7.6 ± 4.2% with p = 0.006). However, the dapagliflozin group showed a significant reduction in FBS and HbA1c as compared to placebo with p value 0.006 and 0.04 respectively. Body weight was significantly reduced in the dapagliflozin group (from 90 ± 13.5 to 84 ± 11.6) as compared to the placebo group (from 85 ± 17.8 to 85.5 ± 13.7) with p = 0.002. BMI also reduced in the dapagliflozin group (from 29.5 ± 2.5 to 26.5 ± 3.5) versus the placebo group (from 31.5 ± 3.0 to 29.5 ± 4.2) with p = 0.002. There was also significant reduction in ALT in the dapagliflozin group from 69 ± 15.5 to 52 ± 12.8 versus placebo from 68 ± 20.5 with p = 0.04 and AST from 74 ± 13 to 47 ± 13.5 versus placebo from 71 ± 12.5 to 65 ± 10.5 with p = 0.02
Conclusion
Dapagliflozin has a strong potential to reverse NAFLD-associated changes in type 2 diabetic patients.
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Data availability
Can be provided on request.
References
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epideminiology of non alcoholic fatty liver disease- meta-analytic assessment of prevalence, incidence and outcomes. Hepatolgy. 2016;64(1):73–84. https://doi.org/10.1002/hep.28431.
Ashtaris S, Pourhoseingholi MA, Zali MR. Non alcoholic fatty liver disease in Asia: prevention and planning. World J Hepatol. 2015;7(13):1788–96. https://doi.org/10.4254/wjh.v7.i13.1788.
Lee YH, Cho Y, Lee BW, Park CY, Lee DH, Cha BS, Rhee EJ. Nonalcoholic fatty liver disease in diabetes. Part I: epidemiology and diagnosis. Diabetes Metab J. 2019;43(1):31–45. https://doi.org/10.4093/dmj.2019.0011.
Prat LI, Tsochatzis EA. The effect of antidiabetic medications on non-alcoholic fatty liver disease (NAFLD). Hormones. 2018;17(2):219–29. https://doi.org/10.1007/s42000-018-0021-9.
Tacelli M, Celsa C, Magro B, Giannetti A, Pennisi G, Spatola F. Antidiabetic drugs in NAFLD: the accomplishment of two goals at once? Pharmaceuticals. 2018;11(4):121.
Bonora BM, Avogaro A, Fadini GP. Extraglycemic effects of SGLT2 inhibitors: a review of the evidence. Diab Metab Syndr Obes: Targets Ther. 2020;13:161.
Ghezzi C, Amy SY, Hirayama BA, Kepe V, Liu J, Scafoglio C. Dapagliflozin binds specifically to sodium-glucose co transporter 2 in the proximal renal tubule. J Am Soc Nephrol. 2017;28(3):802–10.
Dokmak A, Almeqdadi M, Trivedi H, Krishnan S. Rise of sodium-glucose cotransporter 2 inhibitors in the management of nonalcoholic fatty liver disease. W J Hepatol. 2019;11(7):562.
Yanai H, Hakoshima M, Katsuyama H. The possible mechanisms for improvement of liver function due to sodium-glucose cotransporter-2 inhibitors. J Clin Med Res. 2019;11(11):769.
Pereira MJ, Eriksson JW. Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs. 2019;79(3):219–30.
Wong VW, Chan RS, Wong GL, Cheung BH, Chu WC, Yeung DK. Community based life style modification program for non alcoholic fatty liver disease: a randomized controlled trials. J Hepatol. 2013;59(3):536–42. https://doi.org/10.1016/j.jhep.2013.04.013.
Gomez EV, Perez YM, Berot LC, Gonzalez AT, Oramas BG, Fabian LG. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gasteroenterol. 2015;149(2):367–78. https://doi.org/10.1053/j.gastro.2015.04.005.
Cai X, Yang W, Gao X, Chen Y, Zhou L, Zhang S, Han X, Ji L. The association between the dosage of SGLT2 inhibitor and weight reduction in type 2 diabetes patients: a meta-analysis. Obes. 2018;26(1):70–80.
Choi DH, Jung CH, Mok JO, Kim CH, Kang SK, Kim BY. Effect of dapagliflozin on alanine aminotransferase improvement in type 2 diabetes mellitus with non-alcoholic fatty liver disease. Endocrinol Metab. 2018;33(3):387–94.
Koutsovasilis A, Sotiropoulos A, Pappa M, Papadaki D, Kordinas V, Tamvakos C. The effect of lixisenatide and dapagliflozin in nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus compared with sitagliptin and pioglitazone. Diabetes. 2018;67(Supplement 1). .https://doi.org/10.2337/db18-1235-P.
Shimizu M, Suzuki K, Kato K, Jojima T, Iijima T, Murohisa T. Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obes Metab. 2019;21(2):285–92.
Itani T, Ishihara T. Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study. Obes Sci Prac. 2018;4(5):477–82.
Seko Y, Sumida Y, Sasaki K, Itoh Y, Iijima H, Hashimoto T. Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials. J Gastroenterol. 2018;53(1):140–51.
Scheen AJ. Effect of sodium-glucose cotransporter type 2 inhibitors on liver fat in patients with type 2 diabetes: hepatic beyond cardiovascular and renal protection? Ann Transl Med. 2018;6(Suppl 1):S68. https://doi.org/10.21037/atm.2018.10.39.
Seko Y, Sumida Y, Tanaka S, Mori K, Taketani H, Ishiba H. Effect of sodium glucose cotransporter 2 inhibitor on liver function tests in Japanese patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus. Hepatol Res. 2017;47(10):1072–8.
Aso Y, Kato K, Sakurai S, Kishi H, Shimizu M, Jojima T. Impact of dapagliflozin, an SGLT2 inhibitor, on serum levels of soluble dipeptidyl peptidase-4 in patients with type 2 diabetes and non-alcoholic fatty liver disease. Int J Clin Pract. 2019;73: e13335. https://doi.org/10.1111/ijcp.13335.
Tobita H, Sato S, Miyake T, Ishihara S, Kinoshita Y. Effects of dapagliflozin on body composition and liver tests in patients with nonalcoholic steatohepatitis associated with type 2 diabetes mellitus: a prospective, open-label, uncontrolled study. Curr Ther Res. 2017;87:13–9.
Raj H, Durgia H, Palui R, Kamalanathan S, Selvarajan S, Kar SS, Sahoo J. SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: a systematic review. World J Diabetes. 2019;10(2):114.
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Hussain, M., Babar, M.Z.M., Tariq, S. et al. Therapeutic outcome of dapagliflozin on various parameters in non-alcoholic fatty liver disease (NAFLD) patients. Int J Diabetes Dev Ctries 42, 290–296 (2022). https://doi.org/10.1007/s13410-021-00980-2
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DOI: https://doi.org/10.1007/s13410-021-00980-2