What side effects are associated with this type of intervention?

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include insulin sensitizers like pioglitazone, which can cause weight gain, peripheral edema, and an increased risk of fractures in women. Metformin, another treatment option, often leads to gastrointestinal side effects such as nausea and diarrhea. GLP-1 receptor agonists may cause gastrointestinal issues like nausea and vomiting, while DPP-4 inhibitors are generally well-tolerated but can occasionally lead to nasopharyngitis and headaches.

What prior FDA approvals exist?

As of now, there are no FDA-approved medications specifically for the treatment of Non-alcoholic Fatty Liver Disease (NAFLD). However, pioglitazone, an insulin sensitizer, has been studied for its potential benefits in treating NAFLD and Non-alcoholic Steatohepatitis (NASH). Other drugs, such as metformin and GLP-1 receptor agonists like liraglutide, have also been explored for their effects on NAFLD due to their roles in improving insulin sensitivity and glycemic control.

What other types of research exist?

Promising novel alternatives to Pioglitazone for Non-alcoholic Fatty Liver Disease patients include glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors). These drugs have shown potential in recent trials for treating NAFLD and NASH.

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Insulin Sensitizer

Pioglitazone for Fatty Liver Disease

Phase 4

Recruiting

Led By Luke Norton, PhD

Research Sponsored by The University of Texas Health Science Center at San Antonio

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Not taking any medication known to affect glucose metabolism other than antidiabetic medications

Age = 18-80 years

Must not have

Alcohol consumption >14 units/week for women and >21 units/week for men

Type 1 diabetes and/or GAD positive subjects

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 16

Awards & highlights

All Individual Drugs Already Approved

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial studies the effects of pioglitazone, a medication that helps the body use insulin more effectively, in patients with type 2 diabetes who have liver conditions like NAFL or NASH. Pioglitazone is a safe and effective option to manage patients with type 2 diabetes and nonalcoholic steatohepatitis (NASH). The goal is to see if this treatment can improve liver function and control blood sugar levels. Researchers will measure various aspects of liver metabolism and insulin sensitivity before and after a few months of treatment.

Who is the study for?

This trial is for adults aged 18-80 with Type 2 Diabetes and moderate to severe fatty liver disease, but not advanced fibrosis or cirrhosis. Participants should be in good health overall, have a BMI of 25-40 kg/m2, and an HbA1c level between 7-10%. They must be on stable diabetes treatment with diet, metformin, or sulfonylurea and not taking other glucose-affecting drugs.

What is being tested?

The study tests the effects of pioglitazone (an insulin sensitizer) compared to a placebo on liver mitochondrial function in patients with Type 2 Diabetes who also have non-alcoholic fatty liver disease. The treatment period lasts for 16 weeks.

What are the potential side effects?

Pioglitazone may cause side effects like fluid retention leading to swelling and weight gain, potential worsening of heart failure, increased risk of bone fractures especially in women, and possible increase in ovulation leading to pregnancy.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am not on medication affecting blood sugar, except for diabetes treatment.

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I am between 18 and 80 years old.

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My liver has a lot of fat but little to no scarring.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I drink less than 14 units of alcohol per week if female, or 21 if male.

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I have Type 1 diabetes or tested positive for GAD antibodies.

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I have a condition where abnormal blood vessels grow in my retina.

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I have been diagnosed with advanced liver scarring.

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I have had severe heart failure in the past.

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I have a chronic liver condition other than NAFLD.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 16

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 16

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 16 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Effect of pioglitazone on hepatic mitochondrial TCA cycle fluxes

Secondary study objectives

Effect of pioglitazone on hepatic gene regulatory networks

Effect of pioglitazone on the hepatic lipidome

Examine the effect of pioglitazone on non-invasive markers of NAFLD

+5 more

Side effects data

From 2014 Phase 4 trial • 20 Patients • NCT01612858

19%

diarrhea

13%

Elevated lactic acid

13%

nausea

13%

Elevated serum creatinine

Bloating

Head trauma accompanied by syncope

vomiting

Baker's cyst

tooth pain

Right upper quadrant abdominal pain

Colitis

100%

80%

60%

40%

20%

Study treatment Arm

Metformin

Pioglitazone

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: NASH TZDExperimental Treatment1 Intervention

T2D with non-alcoholic steatohepatitis (NASH), treated with pioglitazone

Group II: NAFL TZDExperimental Treatment1 Intervention

T2D with non-alcoholic fatty liver (NAFL), treated with pioglitazone

Group III: NASH PlaceboPlacebo Group1 Intervention

T2D with non-alcoholic steatohepatitis (NASH), treated with placebo

Group IV: NAFL PlaceboPlacebo Group1 Intervention

T2D with non-alcoholic fatty liver (NAFL), treated with placebo

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pioglitazone

FDA approved

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include insulin sensitizers like pioglitazone, GLP-1 receptor agonists, and bile acid derivatives such as obeticholic acid. Pioglitazone improves insulin sensitivity, reducing hepatic fat accumulation by enhancing the body's response to insulin. GLP-1 receptor agonists improve glucose and lipid metabolism, reduce hepatic fat content, and improve liver enzymes. Obeticholic acid, a potent farnesoid X receptor agonist, plays a role in lipid and glucose metabolism and has shown efficacy in reducing hepatic fibrosis. These mechanisms are crucial for NAFLD patients as they target the underlying metabolic disturbances, reduce liver fat, and potentially slow disease progression.