SGLT2 Inhibitor Versus Sulfonylurea on Type 2 Diabetes With NAFLD

• Status: Completed
• Trial end date: 2021-06-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kanazawa University
• Collaborator: Kowa Company, Ltd.
• Treatments: 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol; Glimepiride

Criteria

The trial entry criteria are based on:

1. A diagnosis of "definite" NAFLD on liver biopsy obtained within 3 months of screening.

2. ≥20 years of age at the time of the initial screening.

3. Patients with type 2 diabetes mellitus at the time of screening need to have glycemic control (HbA1c of ≥7%) and have been managed by either diet and/or a stable dose of hypoglycemic agents for at least 4 weeks.

Exclusion Criteria

1. 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.

2. Use of agents known to induce steatosis (e.g., valproate, amiodarone, or vitamin E)

3. Hepatic injury caused by substance abuse.

4. Current consumption of more than 20 g of alcohol daily.

5. Hepatic decompensation, such as hepatic encephalopathy, ascites, variceal bleeding

6. Elevated serum bilirubin level of more than two-fold the upper normal limit.

7. Tofogliflozin or glimepiride hypersensitivity or contraindications.

8. History of type 1 diabetes.

9. History of ketoacidosis.

10. History of symptoms of severe hypoglycemia.

11. Treatment with SGLT2 inhibitor including tofogliflozin within 4 weeks of screening.

12. Treatment with glinide and sulfonylurea use within 4 weeks of screening.

13. Concomitant corticosteroid therapy uses within 4 weeks of screening.

14. Poorly controlled unstable diabetes (ketoacidosis or an increase in HbA1c of >3% in the 12 weeks before screening).

15. Poorly controlled hypertension or systolic blood pressure of >160 mmHg or diastolic blood pressure of >100 mmHg.

16. Artificial dialysis or moderate renal dysfunction.

17. Poorly controlled dyslipidemia.

18. Presence of a severe health problem, not being suitable for the study.

19. Pregnant or breastfeeding.

20. Inability to participate in the study (including psychiatric and psychosocial problems), as assessed by the investigators.