Comparison of Tofogliflozin and Glimepiride Effects on Nonalcoholic Fatty Liver Disease in Participants With Type 2 Diabetes: A Randomized, 48-Week, Open-Label, Active-Controlled Trial.
Journal
Diabetes care
ISSN: 1935-5548
Titre abrégé: Diabetes Care
Pays: United States
ID NLM: 7805975
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
received:
01
10
2021
accepted:
21
05
2022
pubmed:
28
7
2022
medline:
9
9
2022
entrez:
27
7
2022
Statut:
ppublish
Résumé
Nonalcoholic fatty liver disease (NAFLD) is a liver phenotype of type 2 diabetes and obesity. Currently, the efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors and sulfonylureas in liver pathology and hepatic gene expression profiles for type 2 diabetes with NAFLD are unknown. We conducted a 48 week, randomized, open-label, parallel-group trial involving participants with biopsy-confirmed NAFLD. A total of 40 participants were randomly assigned to receive once daily 20 mg tofogliflozin or 0.5 mg glimepiride. The primary outcome was the percentage of participants with at least an improvement in all individual scores for histological categories of steatosis, hepatocellular ballooning, lobular inflammation, and fibrosis by at least 1 point. The secondary end points were the changes in liver enzymes, metabolic markers, and hepatic gene expression profiles. Fibrosis scores improved in the tofogliflozin group (60%, P = 0.001), whereas the change from baseline did not differ significantly between the groups (P = 0.172). The histological variables of steatosis (65%, P = 0.001), hepatocellular ballooning (55%, P = 0.002), and lobular inflammation (50%, P = 0.003) were improved in the tofogliflozin group, whereas only hepatocellular ballooning was improved in the glimepiride group (25%, P = 0.025). Hepatic gene expression profiling revealed histology-associated signatures in energy metabolism, inflammation, and fibrosis that were reversed with tofogliflozin. Tofogliflozin and, to a lesser degree, glimepiride led to liver histological and metabolic improvement in participants with type 2 diabetes and NAFLD, with no significant difference between the agents. The hepatic expression of the genes involved in energy metabolism, inflammation, and fibrosis was well correlated with liver histological changes and rescued by tofogliflozin. We need further confirmation through long-term larger-scale clinical trials of SGLT2 inhibitors.
Identifiants
pubmed: 35894933
pii: 147324
doi: 10.2337/dc21-2049
pmc: PMC9472500
doi:
Substances chimiques
Benzhydryl Compounds
0
Glucosides
0
Sulfonylurea Compounds
0
glimepiride
6KY687524K
6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
P8DD8KX4O4
Banques de données
ClinicalTrials.gov
['NCT02649465']
UMIN-CTR
['UMIN-000020544']
figshare
['10.2337/figshare.20068982']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2064-2075Informations de copyright
© 2022 by the American Diabetes Association.
Références
Front Cell Dev Biol. 2016 Jan 28;3:83
pubmed: 26858947
J Clin Invest. 2014 Feb;124(2):509-14
pubmed: 24463448
N Engl J Med. 2010 May 6;362(18):1675-85
pubmed: 20427778
Am J Gastroenterol. 1999 Sep;94(9):2467-74
pubmed: 10484010
Diabetologia. 2018 Dec;61(12):2461-2498
pubmed: 30288571
Diabetes Care. 2019 May;42(5):931-937
pubmed: 30885955
Diabetologia. 2014 May;57(5):878-90
pubmed: 24407920
PLoS One. 2016 Jan 05;11(1):e0146337
pubmed: 26731267
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Diabetes Care. 2017 Mar;40(3):419-430
pubmed: 28223446
Diabetes Care. 2010 Feb;33(2):284-6
pubmed: 19880582
Hepatol Commun. 2022 Jan;6(1):120-132
pubmed: 34558835
J Clin Endocrinol Metab. 2012 Mar;97(3):1020-31
pubmed: 22238392
Hepatol Res. 2019 Jan;49(1):64-71
pubmed: 30051943
Diabetes Obes Metab. 2019 Apr;21(4):812-821
pubmed: 30447037
Hepatology. 2005 Jun;41(6):1313-21
pubmed: 15915461
Hepatology. 2017 May;65(5):1557-1565
pubmed: 28130788
Dig Liver Dis. 2021 Jan;53(1):44-51
pubmed: 32912770
J Clin Invest. 2014 Feb;124(2):499-508
pubmed: 24463454
Hepatol Int. 2020 Dec;14(6):889-919
pubmed: 33006093
J Hepatol. 2016 Jun;64(6):1388-402
pubmed: 27062661
Nucleic Acids Res. 2013 May 1;41(10):e108
pubmed: 23558742
N Engl J Med. 2006 Nov 30;355(22):2297-307
pubmed: 17135584
Gastroenterology. 2015 Aug;149(2):389-97.e10
pubmed: 25935633
Diabetologia. 2018 Sep;61(9):1923-1934
pubmed: 29971527
Hepatology. 2018 Jan;67(1):328-357
pubmed: 28714183
Diabetes Ther. 2020 Feb;11(2):549-560
pubmed: 31956961
J Hepatol. 2010 Nov;53(5):817-26
pubmed: 20739080
J Gastroenterol. 2007 Apr;42(4):312-7
pubmed: 17464461
Hepatol Commun. 2017 Feb 27;1(1):46-52
pubmed: 29404432
Diabetes Care. 2018 Aug;41(8):1801-1808
pubmed: 29895557
Diabetes Care. 2017 Oct;40(10):1364-1372
pubmed: 28751548
Dig Dis Sci. 2020 Feb;65(2):623-631
pubmed: 30684076
N Engl J Med. 2021 Mar 25;384(12):1113-1124
pubmed: 33185364
Ann Pharmacother. 2021 Jan;55(1):65-79
pubmed: 32571083
BMJ Open Gastroenterol. 2016 Mar 18;3(1):e000075
pubmed: 27110380
Hepatology. 2012 Apr;55(4):1298-300
pubmed: 22461078
Eur J Pharmacol. 2015 May 5;754:19-24
pubmed: 25701721
Endocrinol Metab (Seoul). 2018 Sep;33(3):387-394
pubmed: 30229578
Lancet. 2013 Sep 14;382(9896):941-50
pubmed: 23850055
Hepatology. 2018 Jan;67(1):123-133
pubmed: 28802062
Lancet. 2016 Feb 13;387(10019):679-690
pubmed: 26608256
Nat Commun. 2018 Oct 22;9(1):4383
pubmed: 30348985
Hepatology. 2010 Feb;51(2):445-53
pubmed: 19877169
Hepatology. 2004 Aug;40(2):366-75
pubmed: 15368441
Dig Liver Dis. 2017 Mar;49(3):235-240
pubmed: 28089623
Lancet. 2015 Mar 14;385(9972):956-65
pubmed: 25468160
Gastroenterology. 2016 Mar;150(3):626-637.e7
pubmed: 26677985
Hepatol Res. 2017 Sep;47(10):1072-1078
pubmed: 27925353
J Diabetes Investig. 2019 Jul;10(4):1004-1011
pubmed: 30461221
Diabetes Obes Metab. 2018 Feb;20(2):438-442
pubmed: 28719078