Metformin for the Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) (NAFLD)

Hyperinsulinemia and Insulin Resistance in Nonalcoholic Fatty Liver Disease. Metformin for the Treatment of Nonalcoholic Fatty Liver Disease: A Randomized, Double-Blinded, Placebo-Controlled Trial

The purpose of this study is to find out if Metformin is safe and useful in the treatment of NAFLD.

Study Overview

• Status: Terminated
• Conditions: Fatty Liver
• Intervention / Treatment: Drug: Glucophage (Metformin); Drug: Placebo

Detailed Description

NAFLD is a poorly understood disease which may cause an enlarged liver, abnormal liver test results, and scarring of the liver. It may occur more often in people with obesity, high levels of cholesterol (blood fats), diabetes (high blood sugar), or the insulin resistance syndrome (where a person's body does not respond to the hormone insulin which helps keep blood sugar levels normal). Currently, no effective drug treatment for NAFLD exists. There is increasing evidence that NAFLD may be a condition due to a problem with metabolism (the way your body uses energy). Previous studies have shown that high glucose (sugar) levels may play an important role in the development of fatty liver disease. Medications that decrease your natural glucose level may reduce the amount of fat in the liver and, therefore, might be useful in the treatment of NAFLD. Metformin, a drug approved by the U.S. Food and Drug Administration (FDA) for use in patients with diabetes, has been shown to improve fatty liver in animals and in a small number of human beings.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• biopsy-proven NAFLD, determined within 12 months of study initiation

Exclusion Criteria:

• > 20 grams of alcohol/day
• impaired oral glucose tolerance test
• known diagnosis of diabetes mellitus
• hepatitis C infection
• cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsule	Drug: Placebo; placebo 2000 mg daily for 12 months
Active Comparator: Metformin; Metformin XR (extended-release) 2000 mg daily	Drug: Glucophage (Metformin); metformin XR 2000 mg daily for 12 months; Other Names: Glumetza; Fortamet; Riomet; metformin; Glucophage XR (extended-release)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Study Endpoints Will Include Measurements of Insulin Sensitivity, Hepatic Insulin Clearance, and Altered Parameters of Lipid Metabolism, Changes in the Histological Features That Define NAFLD, and Quantitative Measurements of Visceral and Peripheral Fat.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Tests the Postulate That Metformin Will Improve Insulin Sensitivity in NAFLD. Also Test the Postulate That Improving IR (Insulin Resistance) With an Insulin Sensitizing Agent Will Improve Biochemical and Histological Features of NAFLD.	24 months
Determine if Metformin Improves the Altered Parameters of Lipid Metabolism as Compared to Placebo.	24 months
Measure the Differential Effects of IR and Lipid Metabolism on Peripheral Mononuclear Cell (PBMC) Inflammatory Response and the Associated Hepatocyte Mitochondrial Ultrastructure and Measures of Oxidative Stress	24 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Manal F Abdelmalek, MD, MPH, Duke University Medical Center, Department of Medicine, Division of Gastroenterology

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: August 13, 2008
• First Submitted That Met QC Criteria: August 14, 2008
• First Posted (Estimated): August 15, 2008

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: nonalcoholic fatty liver disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: Pro00006196; K23DK062116 (U.S. NIH Grant/Contract)