Empagliflozin for Fatty Liver

(SHIELD Trial)

Overseen By Angie Figueroa, MS, CCRP

Age: < 65

Sex: Any

Trial Phase: Phase 2

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

Must not be taking: Weight loss meds, Vitamin E, Metformin, others

Disqualifiers: Diabetes, Major psychiatric disorder, others

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

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 aims to test the effectiveness and safety of empagliflozin for treating non-alcoholic fatty liver disease (NAFLD) in adolescents with obesity. The study will compare empagliflozin to a placebo (a pill with no active medication) to determine if it reduces liver fat. Adolescents with obesity, diagnosed with NAFLD, and who have attempted lifestyle changes to manage their condition might be suitable for this trial. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as weight loss medications, Vitamin E supplements, metformin, and any medications associated with weight gain, if you have used them recently. If you are on anti-hypertensive or lipid medications, you must have started them at least 3 months before enrolling.

Is there any evidence suggesting that empagliflozin is likely to be safe for humans?

Research has shown that empagliflozin is generally safe for people. Previous studies have found that it can reduce liver fat and improve liver function without causing serious side effects. In one study, participants experienced a 2.39% decrease in liver fat, while those not using the treatment saw an increase. This suggests that empagliflozin is well-tolerated.

Another study found that empagliflozin aids in weight loss, lowers blood sugar levels, and improves liver health in people with non-alcoholic fatty liver disease (NAFLD). These studies did not report any major side effects, indicating that the treatment is safe for use in clinical trials.

The FDA has also approved empagliflozin for treating type 2 diabetes, which supports its safety. While more research is needed to confirm these findings, current evidence suggests that empagliflozin is a promising and safe option for managing liver issues related to obesity in adolescents. ^{1 2 3 4 5}

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

Empagliflozin is unique because it targets fatty liver disease by reducing excess liver fat through a novel mechanism. Unlike current treatments that primarily focus on lifestyle changes and weight loss, empagliflozin is a medication originally used for diabetes management. It works by promoting the excretion of excess glucose via urine, which indirectly reduces liver fat, offering a fresh approach to tackling fatty liver. Researchers are excited because this medication could provide a pharmacological option for patients who struggle with lifestyle modifications alone.

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

Research has shown that empagliflozin, which participants in this trial may receive, can help reduce liver fat and improve liver health in people with non-alcoholic fatty liver disease (NAFLD). One study found that liver fat decreased by about 2.39% in people taking empagliflozin, while those on a placebo experienced an increase. Another study found that it improved liver function and aided weight loss, which can benefit NAFLD management. Empagliflozin may also support better liver health in people with type 2 diabetes and NAFLD. While some studies show positive results, others suggest it might not directly change liver tissue. Overall, early findings are promising for empagliflozin's role in treating liver issues in people with obesity. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for obese adolescents with non-alcoholic fatty liver disease (NAFLD). Participants must be aged 16 to less than 21, have a BMI >30 or above the 95th percentile for their age, and show no signs of diabetes. They should have tried lifestyle changes to manage obesity or NAFLD and have elevated liver enzymes. Those with severe fluctuations in liver enzyme tests or other health issues are excluded.

Inclusion Criteria

My BMI is over 30 or above the 95th percentile for my age.

My physical development is beyond the early stages of puberty.

My fasting blood sugar level is below 100 mg/dL.

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, 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

Trial Overview

The study is testing Empagliflozin, an SGLT2 inhibitor, against a placebo to see if it can help treat NAFLD in overweight teens. It's a randomized trial where neither the participants nor the researchers know who gets the real medicine versus a dummy pill.

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

Who Is Running the Clinical Trial?

Ann & Robert H Lurie Children's Hospital of Chicago

Lead Sponsor

Trials

275

Recruited

5,182,000+

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]

In a study involving male mice on a high-fat diet, empagliflozin treatment for 5 weeks led to improved glucose tolerance, increased energy expenditure by 4%, and reduced body mass by 5%, indicating its potential efficacy in managing metabolic health.

Empagliflozin also reduced the expression of genes associated with liver fat production and endoplasmic reticulum stress, suggesting it may help prevent the progression of non-alcoholic fatty liver disease (NAFLD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empaglifozin mitigates NAFLD in high-fat-fed mice by alleviating insulin resistance, lipogenesis and ER stress. Petito-da-Silva, TI., Souza-Mello, V., Barbosa-da-Silva, S.[2020]

Dapagliflozin significantly reduces liver enzymes (ALT and AST) and improves metabolic outcomes, such as insulin resistance and body weight, in patients with nonalcoholic fatty liver disease (NAFLD), based on a meta-analysis of seven trials involving 390 participants.

While dapagliflozin shows efficacy in improving liver function and metabolic health, it may also lead to an increase in total cholesterol levels, with no significant difference in adverse events compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dapagliflozin in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Sun, L., Deng, C., Gu, Y., et al.[2022]

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]

Dapagliflozin significantly reduced liver enzymes and metabolic indicators in adults with nonalcoholic fatty liver disease (NAFLD), based on a systematic review of 11 studies involving 839 patients.

The treatment improved body weight and composition without increasing adverse events, suggesting it is a safe and effective option for managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin for nonalcoholic fatty liver disease: A systematic review and meta-analysis. He, K., Li, J., Xi, W., et al.[2022]

In a study of 240 NAFLD patients with type 2 diabetes, empagliflozin (EMPA) significantly reduced liver fat content by 8.73%, outperforming both ursodeoxycholic acid (UDCA) and placebo, indicating its efficacy in managing liver steatosis.

While EMPA improved liver fat reduction and beta-cell function, UDCA was more effective in reducing liver fibrosis scores and insulin resistance, suggesting that both treatments have unique benefits in managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of an SGLT2 Inhibitor versus Ursodeoxycholic Acid on Liver Steatosis in Diabetic Patients. Elhini, SH., Wahsh, EA., Elberry, AA., et al.[2023]

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]

In a study of 63 type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD), the combination therapy of empagliflozin and metformin significantly improved liver health markers, including reduced liver steatosis and ALT levels, compared to metformin alone after 6 months.

Patients receiving the combination therapy also experienced notable reductions in body mass index (BMI) and glycated hemoglobin, indicating improved overall metabolic control and liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a Combination of Empagliflozin Plus Metformin vs. Metformin Monotherapy on NAFLD Progression in Type 2 Diabetes: The IMAGIN Pilot Study. Caturano, A., Galiero, R., Loffredo, G., et al.[2023]

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 one-year study involving 24 patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, treatment with empagliflozin significantly improved markers of liver inflammation, function, and fibrosis.

Key improvements included reductions in liver enzymes and insulin resistance, as well as enhanced liver function as indicated by the ALBI score, demonstrating empagliflozin's potential as an effective therapy for managing NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term empagliflozin therapy improves levels of hepatic fibrosis marker in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus. Shinozaki, S., Tahara, T., Lefor, AK., et al.[2021]

Citations

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Empagliflozin caused an absolute reduction of 2.39% ± 0.79% in liver fat content compared with an increase of 0.91% ± 0.64% in participants ...

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These findings suggest that Empagliflozin could be an effective adjunctive therapy for managing liver dysfunction in T2DM patients with NAFLD.

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sciencedirect.com

sciencedirect.com/science/article/pii/S1658361225000770

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sciencedirect.com/science/article/pii/S1590865821007337

Meta-Analysis The safety and efficacy evaluation of sodium ...

The meta-analysis showed that SGLT2i could significantly improve BMI, blood glucose, liver function and liver fibrosis in patients with NAFLD, while the ...