SGLT2 Inhibitors for Non-Alcoholic Fatty Liver Disease

(SLIDE Trial)

Recruiting at 1 trial location

Overseen By Justin Ryder, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago

Must not be taking: Weight loss meds, Metformin

Disqualifiers: Diabetes, Major psychiatric disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests empagliflozin, a medication that helps remove extra sugar through urine, in adolescents with obesity and a specific liver condition (NAFLD). The medication works by blocking a protein in the kidneys to help remove sugar from the body. Empagliflozin has been shown to reduce body weight, improve glucose tolerance, and decrease blood pressure in various studies.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as weight loss drugs, metformin, and vitamin E supplements, at least 6 months before joining. If you've recently started anti-hypertensive or lipid medications, you may also need to wait 3 months before enrolling.

Is empagliflozin safe for humans?

Empagliflozin, a type of SGLT2 inhibitor, has been studied in clinical trials and is generally considered safe for humans, with trials showing it can reduce liver fat and improve liver enzyme levels in patients with non-alcoholic fatty liver disease and type 2 diabetes. ^{1 2 3 4 5}

How is the drug empagliflozin unique for treating non-alcoholic fatty liver disease?

Empagliflozin is unique because it is a type of drug called an SGLT2 inhibitor, which is primarily used to treat type 2 diabetes by helping the kidneys remove sugar from the body. Unlike other treatments for non-alcoholic fatty liver disease, empagliflozin also reduces liver fat and improves liver health, making it a novel option for patients with both diabetes and liver issues. ^{3 4 6 7 8}

What data supports the effectiveness of the drug Empagliflozin for treating Non-Alcoholic Fatty Liver Disease?

Research shows that Empagliflozin, a type of SGLT2 inhibitor, can reduce liver fat and improve liver health in people with Non-Alcoholic Fatty Liver Disease (NAFLD), both with and without type 2 diabetes. Studies found it significantly decreased liver enzyme levels and liver fat content, suggesting it could be a promising treatment option for NAFLD. ^{1 2 3 4 9}

Who Is on the Research Team?

Justin Ryder, PhD

Principal Investigator

Ann & Robert H Lurie Children's Hospital of Chicago

Are You a Good Fit for This Trial?

Adolescents aged 12-19 with obesity and non-alcoholic fatty liver disease (NAFLD) can join. They must have high liver enzymes or a confirmed diagnosis of NAFLD/NASH, no significant alcohol intake, no metal implants incompatible with MRI, not pregnant nor planning to be, and without major organ dysfunction or other serious health issues.

Inclusion Criteria

My body shows early signs of puberty.

My BMI is in the obesity range according to my age and sex.

I am willing to follow specific lifestyle guidelines during the study.

Exclusion Criteria

Impaired fasting glucose (>100 mg/dL)

INR 1.3

I have urinary or genital issues that increase my risk of infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive empagliflozin or placebo daily for 26 weeks, with lifestyle/behavioral counseling

26 weeks

Regular visits for physical exams, lab tests, and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin
• Placebo Oral Tablet

Trial Overview The trial is testing Empagliflozin against a placebo to see if it helps treat NAFLD in obese teens. Participants are randomly assigned to either the drug or placebo group without knowing which one they're getting.

How Is the Trial Designed?

Group I: Study intervention Experimental Treatment 1 Intervention

Empagliflozin 10 mg will be taken daily

Group II: Control arm Placebo Group 1 Intervention

Placebo oral tablet will be taken daily

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

Ann & Robert H Lurie Children's Hospital of Chicago

Lead Sponsor

Trials

275

Recruited

5,182,000+

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Empagliflozin significantly reduces body mass index (BMI), liver stiffness measurement (LSM), aspartate aminotransferase (AST), and insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD), based on a review of four randomized controlled trials involving 244 patients.

The findings suggest that empagliflozin improves liver health and metabolic parameters in NAFLD patients, indicating its potential as a new treatment option, although further research is needed to confirm its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Empagliflozin on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Zhang, Y., Liu, X., Zhang, H., et al.[2022]

In a 24-week trial involving 106 patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM), empagliflozin showed a borderline significant reduction in liver fat content compared to placebo, indicating its potential efficacy in improving liver steatosis.

Empagliflozin also significantly reduced liver stiffness compared to pioglitazone, along with notable decreases in body weight and visceral fat, suggesting it may be a more effective treatment option for managing NAFLD in T2DM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Chehrehgosha, H., Sohrabi, MR., Ismail-Beigi, F., et al.[2021]

Empagliflozin treatment in a study of 7020 participants with type 2 diabetes and cardiovascular disease showed a slight reduction in liver fat (steatosis) risk, but did not significantly improve the risk of advanced liver fibrosis over time compared to placebo.

The benefits of empagliflozin on cardiorenal outcomes and overall mortality were consistent across different levels of liver fat and fibrosis risk, suggesting that its protective effects on heart and kidney health are independent of liver fat levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes. Kahl, S., Ofstad, AP., Zinman, B., et al.[2022]

SGLT-2 inhibitors, tested in 12 randomized controlled trials involving 850 overweight or obese individuals with NAFLD, significantly reduced liver enzyme levels and liver fat content over a median treatment period of 24 weeks.

Specifically, treatment with SGLT-2 inhibitors led to a decrease in serum alanine aminotransferase by 10.0 IU/L and gamma-glutamyltransferase by 14.49 IU/L, indicating their potential efficacy in managing nonalcoholic fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials. Mantovani, A., Petracca, G., Csermely, A., et al.[2021]

In a study of 84 patients with well-controlled type 2 diabetes, the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) significantly reduced liver fat content by 1.8% compared to placebo over 24 weeks, indicating its efficacy in managing liver health in diabetes.

EMPA treatment also resulted in a notable weight loss of 2.5 kg and improved levels of uric acid and adiponectin, suggesting additional metabolic benefits, even though it did not change tissue-specific insulin sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial. Kahl, S., Gancheva, S., Straßburger, K., et al.[2020]

Empagliflozin (Jardiance) is a new medication classified as an SGLT2 inhibitor, specifically designed to help manage blood sugar levels in individuals with type-2 diabetes.

This medication not only aids in lowering blood glucose but also has potential benefits for heart health, making it a promising option for patients with diabetes at risk for cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. Ndefo, UA., Anidiobi, NO., Basheer, E., et al.[2020]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Empagliflozin on Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin on Liver Steatosis and Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease Without Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials. [2021]

6. Uganda pubmed.ncbi.nlm.nih.gov

Empagliflozin for the treatment of non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Empagliflozin (Jardiance): A Novel SGLT2 Inhibitor for the Treatment of Type-2 Diabetes. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial). [2022]