sorbitol and Fatty Liver, Nonalcoholic studies

Research Excerpts

Excerpt	Relevance	Reference
"This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD)."	9.27	Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective randomized controlled pilot study. ( Fushimi, N; Hachiya, H; Ito, S; Kawai, H; Kawai, M; Mori, A; Ohashi, N; Shibuya, T; Yoshida, Y, 2018)
"This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD)."	5.27	Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective randomized controlled pilot study. ( Fushimi, N; Hachiya, H; Ito, S; Kawai, H; Kawai, M; Mori, A; Ohashi, N; Shibuya, T; Yoshida, Y, 2018)
"SGL5213 and miglitol improved obesity, liver dysfunction, insulin resistance, and the NAFLD severity."	4.02	Protective effect of SGL5213, a potent intestinal sodium-glucose cotransporter 1 inhibitor, in nonalcoholic fatty liver disease in mice. ( Honda, Y; Imajo, K; Iwaki, M; Kessoku, T; Kobayashi, T; Nagashima, Y; Nakajima, A; Nogami, A; Ogawa, Y; Ozaki, A; Saito, S; Tomeno, W; Yoneda, M, 2021)
"She had been suffering from type 2 diabetes mellitus since the age of 50 years."	1.56	Long-term luseogliflozin therapy improves histological activity of non-alcoholic steatohepatitis accompanied by type 2 diabetes mellitus. ( Fujimori, N; Horiuchi, A; Joshita, S; Kato, N; Kimura, T; Kuribayashi, N; Matsumoto, A; Sano, K; Sugiura, A; Takahashi, Y; Tanaka, E; Tanaka, N; Umemura, T; Yamazaki, T, 2020)

Research

Studies (6)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Change From Baseline in Alanine Aminotransferase (ALT) at Week 12

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	1 (16.67)	24.3611
2020's	5 (83.33)	2.80

Authors	Studies
Harrison, SA	1
Manghi, FP	1
Smith, WB	1
Alpenidze, D	1
Aizenberg, D	1
Klarenbeek, N	1
Chen, CY	1
Zuckerman, E	1
Ravussin, E	1
Charatcharoenwitthaya, P	1
Cheng, PN	1
Katchman, H	1
Klein, S	1
Ben-Ari, Z	1
Mendonza, AE	1
Zhang, Y	1
Martic, M	1
Ma, S	1
Kao, S	1
Tanner, S	1
Pachori, A	1
Badman, MK	1
He, Y	1
Ukomadu, C	1
Sicard, E	1
Nakagawa, T	1
Johnson, RJ	1
Andres-Hernando, A	1
Roncal-Jimenez, C	1
Sanchez-Lozada, LG	1
Tolan, DR	1
Lanaspa, MA	1
Jeong, SW	1
Honda, Y	1
Ozaki, A	1
Iwaki, M	1
Kobayashi, T	1
Nogami, A	1
Kessoku, T	1
Ogawa, Y	1
Tomeno, W	1
Imajo, K	1
Yoneda, M	1
Saito, S	1
Nagashima, Y	1
Nakajima, A	1
Shibuya, T	1
Fushimi, N	1
Kawai, M	1
Yoshida, Y	1
Hachiya, H	1
Ito, S	1
Kawai, H	1
Ohashi, N	1
Mori, A	1
Fujimori, N	1
Tanaka, N	1
Kimura, T	1
Sano, K	1
Horiuchi, A	1
Kato, N	1
Takahashi, Y	1
Kuribayashi, N	1
Sugiura, A	1
Yamazaki, T	1
Joshita, S	1
Umemura, T	1
Matsumoto, A	1
Tanaka, E	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A 12-week Randomized, Patient and Investigator Blinded, Placebo-controlled, Parallel Group Study to Investigate the Efficacy of LIK066 in Obese Patients With Non-alcoholic Steatohepatitis (NASH)[NCT03205150]	Phase 2	107 participants (Actual)	Interventional	2017-10-04	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Alanine aminotransferase (ALT) is an enzyme found primarily in the liver. ALT is increased with liver damage. In this study, the blood levels of ALT was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits. (NCT03205150)
Timeframe: Baseline, Week 12

Change From Baseline in Aspartate Aminotransferase (AST) at Week 12

Intervention	Units per Liter (U/L) (Mean)
LIK066 30 mg	-22.06
LIK066 150 mg	-30.41
Placebo	-8.77

Aspartate aminotransferase (AST) is an enzyme found in many cells of the body specifically those of the liver, heart and skeletal muscle. In healthy individuals, levels of AST in the blood are low. When liver or muscle cells are injured, they release AST into the blood. In this study, the blood levels of AST was used to detect liver injury. Baseline is defined as the mean of measurements taken at the Screening and Baseline visits. (NCT03205150)
Timeframe: Baseline, Week 12

Change From Baseline in Non-invasive Markers of Hepatic Fibrosis: Enhanced Liver Fibrosis Test (ELF) Score at Week 12

Intervention	Units per liter (U/L) (Mean)
LIK066 30 mg	-13.45
LIK066 150 mg	-17.01
Placebo	-2.30

The markers of fibrosis assessed in this test comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP); these are components of the extracellular matrix and basement sinusoidal membrane of the liver and are elevated during fibrogenesis as a result of activation of the hepatic stellate cell. The ELF test is a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis. A negative change from Baseline indicates decreased fibrosis. (NCT03205150)
Timeframe: Baseline, Week 12

Change From Baseline in Percent Liver Fat at Week 12

Intervention	scores on a scale (Mean)
LIK066 30 mg	-0.2
LIK066 150 mg	-0.1
Placebo	0.1

Percent (%) Liver fat was measured by Magnetic Resonance Imaging Proton Density Liver Fat Fraction(MRIPDFF). Patients underwent magnetic resonance imaging twice during the course of the study ( baseline and end of treatment) to quantitate liver fat. (NCT03205150)
Timeframe: Baseline, Week 12

Change From Baseline in the Concentration of Hyaluronic Acid at Week 12.

Intervention	Percentage of Liver Fat (Mean)
LIK066 30 mg	-4.40
LIK066 150 mg	-6.92
Placebo	-2.67

Hyaluronic Acid is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). (NCT03205150)
Timeframe: Baseline, Week 12

Change From Baseline in the Concentration of Procollagen Type Iii N-Terminal Peptide (PIIINP) at Week 12.

Intervention	ug/L (Mean)
LIK066 30 mg	-3.4
LIK066 150 mg	0.4
Placebo	4.7

PIIINP is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). (NCT03205150)
Timeframe: Baseline, Week 12

Change From Baseline in the Concentration of Tissue Inhibitor Of Metalloproteinase 1 (TIMP-1) at Week 12.

Intervention	ug/L (Mean)
LIK066 30 mg	-1.7
LIK066 150 mg	-1.2
Placebo	0.3

TIMP-1 is a non-invasive marker of liver fibrosis. It was accessed by Enhanced liver fibrosis Test (ELF). (NCT03205150)
Timeframe: Baseline, Week 12

Percent Change From Baseline in Total Body Weight at Week 12

Intervention	ug/L (Mean)
LIK066 30 mg	-3.0
LIK066 150 mg	-10.9
Placebo	10.3

Body weight (to the nearest 0.1 kilogram [kg] was measured on a calibrated scale. The measurement was performed with the study subject in underwear and without shoes; or while wearing minimal indoor clothing. (NCT03205150)
Timeframe: Baseline, Week 12

Pharmacokinetics of LIK066: Observed Area Under the Curve up to the Last Measurable Concentration (AUClast) Following Drug Administration

Intervention	percentage change (Mean)
LIK066 30 mg	-3.48
LIK066 150 mg	-4.51
Placebo	-0.33

AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (hour*ng/mL) (NCT03205150)
Timeframe: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)

Pharmacokinetics of LIK066: Observed Maximum Plasma Concentration (Cmax) Following Drug Administration

Intervention	hour*ng/mL (Mean)
LIK066 30 mg	1280
LIK066 150 mg	5770

Cmax is the observed maximum plasma concentration following drug administration (ng/mL) (NCT03205150)
Timeframe: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)

Pharmacokinetics of LIK066: Observed Maximum Time Duration of Maximum Concentration (Tmax) Following Drug Administration

Intervention	ng/mL (Mean)
LIK066 30 mg	405
LIK066 150 mg	1810

Tmax is the time to reach the maximum concentration after drug administration (hour). The time points presented are the actual and not the planned time points. (NCT03205150)
Timeframe: Day 56 (pre-dose and 1, 2, 4 and 6 hours post-dose)

Article	Year
Licogliflozin for nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a study. Nature medicine, 2022, Volume: 28, Issue:7 Topics: Alanine Transaminase; Anhydrides; Double-Blind Method; Humans; Non-alcoholic Fatty Liver Disease; So	2022
Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective randomized controlled pilot study. Diabetes, obesity & metabolism, 2018, Volume: 20, Issue:2 Topics: Adiposity; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans	2018

Article	Year
Nonalcoholic Fatty Liver Disease: A Drug Revolution Is Coming. Diabetes & metabolism journal, 2020, Volume: 44, Issue:5 Topics: Anhydrides; Diabetes Mellitus, Type 2; End Stage Liver Disease; Fibroblast Growth Factors; Humans; N	2020
Protective effect of SGL5213, a potent intestinal sodium-glucose cotransporter 1 inhibitor, in nonalcoholic fatty liver disease in mice. Journal of pharmacological sciences, 2021, Volume: 147, Issue:2 Topics: 1-Deoxynojirimycin; Animals; Chronic Disease; Diet, High-Fat; Dietary Sucrose; Disease Models, Anima	2021
Long-term luseogliflozin therapy improves histological activity of non-alcoholic steatohepatitis accompanied by type 2 diabetes mellitus. Clinical journal of gastroenterology, 2020, Volume: 13, Issue:1 Topics: Alanine Transaminase; Aspartate Aminotransferases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase I	2020

sorbitol and Fatty Liver, Nonalcoholic