SGLT2 Inhibitors for Non-Alcoholic Fatty Liver Disease

(SLIDE Trial)

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests empagliflozin, a medication that might help treat non-alcoholic fatty liver disease (NAFLD) in teenagers with obesity. Researchers aim to determine if this medication is safe and effective for improving liver health. Participants will receive either empagliflozin or a placebo (a pill with no active medicine) without knowing which one they are taking. Ideal candidates for this trial are teens diagnosed with obesity and NAFLD who have attempted lifestyle changes to manage these conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that empagliflozin is generally safe. Studies have found that it helps lower markers of liver issues, such as AST and ALT, enzymes related to liver health. Participants taking empagliflozin for type 2 diabetes showed reduced liver fat and improved ALT levels, suggesting potential liver health benefits.

No major safety concerns have emerged in the studies. However, some individuals might experience mild side effects, such as frequent urination or dehydration, as the drug aids in sugar removal through urine.

This treatment is currently in a Phase 2 trial, indicating that earlier studies have already assessed its safety. For those considering joining this trial, current data suggests the treatment is well-tolerated. Discussing any concerns with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NAFLD?

Unlike the standard treatments for non-alcoholic fatty liver disease (NAFLD), which typically focus on lifestyle changes and managing related conditions like diabetes, Empagliflozin offers a novel approach. This drug, primarily a diabetes medication, works by inhibiting the SGLT2 protein, which reduces glucose reabsorption in the kidneys and promotes glucose excretion through urine. Researchers are excited because Empagliflozin's mechanism could also help reduce liver fat and improve liver function, addressing NAFLD directly. This dual action—targeting both blood sugar levels and liver health—could provide a more comprehensive treatment option for patients with NAFLD.

What evidence suggests that Empagliflozin might be an effective treatment for NAFLD?

Research suggests that empagliflozin, which participants in this trial may receive, might help reduce liver fat in people with non-alcoholic fatty liver disease (NAFLD). Some studies have shown it can aid in weight loss and improve liver function. An important finding is that empagliflozin may reduce liver scarring, a type of liver damage. However, not all studies agree; some have found no significant change in liver health. Overall, empagliflozin shows promise as a treatment, but more research is needed to confirm its benefits for NAFLD. Participants in the control arm of this trial will receive a placebo oral tablet. ^{1 2 4 5 6}

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

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]

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]

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]

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 (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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8908261/

Efficacy and Safety of Empagliflozin on Nonalcoholic Fatty ... The results of our research showed that empagliflozin had significant beneficial effects in decreasing body weight and improving liver function, liver fibrosis, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9993318/

Empagliflozin for the treatment of non-alcoholic fatty liver ... Our meta-analysis concludes that empagliflozin demonstrates no beneficial effect on hepatic steatosis or fibrosis as shown by the LSM and CAP score in patients ...

3. diabetesjournals.org diabetesjournals.org/care/article/47/4/668/154175/Empagliflozin-Reduces-Liver-Fat-in-Individuals

Empagliflozin Reduces Liver Fat in Individuals With and ... Empagliflozin is effective in reducing liver fat content in individuals with and without T2D. The decrease in liver fat content is independent of the decrease ...

4. bmcendocrdisord.biomedcentral.com bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-025-01882-8

The effect of empagliflozin on non-alcoholic fatty liver disease ... These findings suggest that Empagliflozin could be an effective adjunctive therapy for managing liver dysfunction in T2DM patients with NAFLD.

5. sciencedirect.com sciencedirect.com/science/article/pii/S3050915725000955

Review Article Evaluating the Comparative Effectiveness of ... Empagliflozin topped FIB-4 score reduction (MD: -0.12, SUCRA: 73.27%), indicating superior anti-fibrotic effects in NAFLD. Clinical Relevance:.

6. diabetesjournals.org diabetesjournals.org/care/article/41/8/1801/36391/Effect-of-Empagliflozin-on-Liver-Fat-in-Patients

Effect of Empagliflozin on Liver Fat in Patients With Type 2 ... When included in the standard treatment for type 2 diabetes, empagliflozin reduces liver fat and improves ALT levels in patients with type 2 diabetes and NAFLD.