SGLT2 Inhibitor Versus Sulfonylurea on Type 2 Diabetes With NAFLD

NCT02649465 | Completed Phase 4 DMC

• 1 other identifier: CRB4180005
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The clinicopathological analyses revealed that reduction in HbA1c and use of insulin independently contribute to the reduction in liver fibrosis scores during the histological course of NAFLD development. These findings led us to hypothesize that glycemic control and insulin ameliorate or protect against the histological progression of liver fibrosis in patients with NAFLD. In the present study, we investigated the efficacy of SGLT2 inhibitor tofogliflozin and sulfonylurea glimepiride, which lower glucose levels similarly with reduction and elevation in circulating insulin levels, respectively, in NAFLD patients with type 2 diabetes for 48 weeks by examining liver histology, as well as hepatic enzymes, metabolic markers, and hepatic gene expression profiles.

Conditions

Non-alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• The improvement in histologic features of NAFLD

  48 weeks

Secondary Outcomes (21)

• Change from baseline in liver enzymes

  48 weeks

• Change from baseline in body composition

  48 weeks

• Change from baseline in fasting plasma glucose level and glucose metabolism assessed with arginine tolerance test

  48 weeks

• Changes from baseline in organ-specific insulin sensitivity and glucagon response during a euglycemic hyperinsulinemic clamp study

  48 weeks

• Change from baseline in lipid profile

  48 weeks

Study Arms (2)

SGLT2 inhibitor

ACTIVE COMPARATOR

N=20 SGLT2 inhibitor dosage (Tofogliflozin): a dose of 20mg once daily for 48 weeks.

Drug: Tofogliflozin

Sulfonylurea

ACTIVE COMPARATOR

N=20 Sulfonylurea (Glimepiride): an initial dose of 0.5 mg once daily for 48 weeks.

Drug: Glimepiride

Interventions

Tofogliflozin DRUG

The group receiving Tofogliflozin (at a dose of 20mg once daily) for 48 weeks

Also known as: DEBERZA

SGLT2 inhibitor

Glimepiride DRUG

Sulfonylurea dosage (Glimepiride): dosing from 0.5 mg for initial 4 weeks. Then, if there is no adverse effect or no improvement of glucose metabolism, glimepiride is escalated to 6 mg once daily.

Sulfonylurea

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Hepatic virus infections (hepatitis B and C, cytomegalovirus, and Epstein-Barr virus), autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, hemochromatosis, alpha 1-antitrypsin deficiency, Wilson's disease, history of parenteral nutrition.
• Use of agents known to induce steatosis (e.g., valproate, amiodarone, or vitamin E)
• Hepatic injury caused by substance abuse.
• Current consumption of more than 20 g of alcohol daily.
• Hepatic decompensation, such as hepatic encephalopathy, ascites, variceal bleeding
• Elevated serum bilirubin level of more than two-fold the upper normal limit.
• Tofogliflozin or glimepiride hypersensitivity or contraindications.
• History of type 1 diabetes.
• History of ketoacidosis.
• History of symptoms of severe hypoglycemia.
• Treatment with SGLT2 inhibitor including tofogliflozin within 4 weeks of screening.
• Treatment with glinide and sulfonylurea use within 4 weeks of screening.
• Concomitant corticosteroid therapy uses within 4 weeks of screening.
• Poorly controlled unstable diabetes (ketoacidosis or an increase in HbA1c of \>3% in the 12 weeks before screening).
• Poorly controlled hypertension or systolic blood pressure of \>160 mmHg or diastolic blood pressure of \>100 mmHg.

Sponsors & Collaborators

• Kanazawa University: lead
• Kowa Company, Ltd.: collaborator

Study Sites (1)

Kanazawa University Graduate School of Medical Sciences

Kanazawa, Ishikawa-ken, 920-8640, Japan

Location

Related Publications (2)

• Takeshita Y, Honda M, Harada K, Kita Y, Takata N, Tsujiguchi H, Tanaka T, Goto H, Nakano Y, Iida N, Arai K, Yamashita T, Mizukoshi E, Nakamura H, Kaneko S, Takamura T. 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. Diabetes Care. 2022 Sep 1;45(9):2064-2075. doi: 10.2337/dc21-2049.

  PMID: 35894933 DERIVED

• Takeshita Y, Kanamori T, Tanaka T, Kaikoi Y, Kita Y, Takata N, Iida N, Arai K, Yamashita T, Harada K, Gabata T, Nakamura H, Kaneko S, Takamura T. Study Protocol for Pleiotropic Effects and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Versus Sulfonylurea in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease. Diabetes Ther. 2020 Feb;11(2):549-560. doi: 10.1007/s13300-020-00762-9. Epub 2020 Jan 20.

  PMID: 31956961 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol; glimepiride

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Toshinari Takamura, MD,PhD

  Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences,

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Disease Control and Homeostasis

Study Record Dates

• First Submitted: January 5, 2016
• First Posted: January 7, 2016
• Study Start: November 11, 2015
• Primary Completion: December 28, 2020
• Study Completion: June 30, 2021
• Last Updated: July 2, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)