Improving Insulin Resistance To Treat Non-Alcoholic Fatty Liver Disease: A Pilot Study
| Status: | Recruiting |
|---|---|
| Conditions: | Endocrine, Gastrointestinal, Gastrointestinal |
| Therapuetic Areas: | Endocrinology, Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 4/21/2016 |
| Start Date: | June 2015 |
| End Date: | June 2017 |
| Contact: | Aren Skolnick, MD |
| Email: | askolnick@nshs.edu |
| Phone: | 516-375-4361 |
Improving Insulin Resistance to Treat Non-Alcoholic Fatty Liver Disease: A Pilot Study
Metformin is being compared to exercise and diet modifications. The researchers are
interested in learning if the addition of metformin to lifestyle modifications is more
helpful in treating the condition or disorder. Although metformin is FDA approved to treat
type 2 diabetes, it is not FDA approved for the treatment of Non-alcoholic fatty liver
(NAFLD) and is considered investigational for the purpose of this study.
interested in learning if the addition of metformin to lifestyle modifications is more
helpful in treating the condition or disorder. Although metformin is FDA approved to treat
type 2 diabetes, it is not FDA approved for the treatment of Non-alcoholic fatty liver
(NAFLD) and is considered investigational for the purpose of this study.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease
in the United States and a common cause of unexplained mildly elevated serum
aminotransferase levels. NAFLD, initially felt to be benign, is now known to potentially
progress to cirrhosis and its complications, including the development of liver cancer.
NAFLD is strongly correlated with Type 2 Diabetes, insulin resistance, and the metabolic
syndrome (1-6). It is hypothesized that the pathogenesis of hepatic injury in NAFLD is due
to insulin resistance and the oxidative stress associated with obesity and metabolic
syndrome (7). No adequate medical treatment has been shown to be effective for the treatment
of NAFLD. Several studies (8-22) have evaluated the effect of metformin in patients with
NAFLD in relation to insulin resistance, Homeostatic Model Assessment Insulin Resistance
Index (HOMA-IR) values, aminotransferase levels, liver morphology, and histological
improvement with treatment. These studies however have shown discrepant results with
relation to aminotransferase levels and only a few studies have been able to evaluate
histological improvement with follow-up biopsies. There have been no studies focusing
specifically on the pre-diabetic population. These patients who are at an increased risk of
progressing to diabetes may exhibit a different response to treatment with metformin than
non-diabetic or diabetic patients. All the studies support the fact that metformin has a
beneficial effect on improving insulin resistance and decreasing the incidence of metabolic
syndrome, but there is no consensus thus far on its influence on NAFLD. The majority of
published studies were limited by small sample size. Randomized controlled trials with
adequate sample size and of longer duration are needed as well as studies assessing
endpoints such as liver morphology and histology. The results of this pilot study are
significant in that metformin may be a relatively safe and inexpensive way, in addition to
lifestyle modifications, to treat NAFLD. The results of this pilot study will pave the way
for the larger power, longer duration study required to answer this question.
in the United States and a common cause of unexplained mildly elevated serum
aminotransferase levels. NAFLD, initially felt to be benign, is now known to potentially
progress to cirrhosis and its complications, including the development of liver cancer.
NAFLD is strongly correlated with Type 2 Diabetes, insulin resistance, and the metabolic
syndrome (1-6). It is hypothesized that the pathogenesis of hepatic injury in NAFLD is due
to insulin resistance and the oxidative stress associated with obesity and metabolic
syndrome (7). No adequate medical treatment has been shown to be effective for the treatment
of NAFLD. Several studies (8-22) have evaluated the effect of metformin in patients with
NAFLD in relation to insulin resistance, Homeostatic Model Assessment Insulin Resistance
Index (HOMA-IR) values, aminotransferase levels, liver morphology, and histological
improvement with treatment. These studies however have shown discrepant results with
relation to aminotransferase levels and only a few studies have been able to evaluate
histological improvement with follow-up biopsies. There have been no studies focusing
specifically on the pre-diabetic population. These patients who are at an increased risk of
progressing to diabetes may exhibit a different response to treatment with metformin than
non-diabetic or diabetic patients. All the studies support the fact that metformin has a
beneficial effect on improving insulin resistance and decreasing the incidence of metabolic
syndrome, but there is no consensus thus far on its influence on NAFLD. The majority of
published studies were limited by small sample size. Randomized controlled trials with
adequate sample size and of longer duration are needed as well as studies assessing
endpoints such as liver morphology and histology. The results of this pilot study are
significant in that metformin may be a relatively safe and inexpensive way, in addition to
lifestyle modifications, to treat NAFLD. The results of this pilot study will pave the way
for the larger power, longer duration study required to answer this question.
Inclusion Criteria:
- subjects between ages 18-80
- diagnosed with NAFLD by alanine aminotransferase
- (ALT) levels >1.5x the upper limit of normal with an otherwise nondiagnostic hepatic
serology workup, ultrasound evidence, and/or histologically confirmed NAFLD within
the past 1 year.
- The upper limit of normal for ALT will be defined as 35 U/L in males and 19 U/L in
females
Exclusion Criteria:
- A prior history of diabetes
- Failure to meet criteria for HbA1C screening
- Evidence of hepatic disorders
- Use of insulin or oral hypoglycemic agents
- eGFR <30
- Blood transfusion within past 3 months
- Steroid use in the past 6 months
- Excessive alcohol use (more than 20g per day in women and more than 30g per day in
men)
- Acute or unstable congestive heart failure
- Age >80 years old
- Lactic acidosis
- Inability to consent due to cognitive impairment.
- Pregnancy
We found this trial at
1
site
Click here to add this to my saved trials
