Semaglutide for Type 2 Diabetes and Fatty Liver in Youth

Overseen By Theresa Goddard

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: Metformin

Must not be taking: Antipsychotics, Steroids

Disqualifiers: Type 1 diabetes, Pancreatitis, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how Semaglutide can help young people with type 2 diabetes and fatty liver disease. Researchers are examining whether this treatment improves insulin-making cell function and reduces liver fat. Participants will receive either the Semaglutide injection or a placebo, which resembles the treatment but lacks the active ingredient. Young individuals aged 10 to 20, who have had type 2 diabetes or prediabetes for two years or less and have a fatty liver, might be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that participants have been on a stable dose of metformin for diabetes for at least 12 months or less. If you are taking other diabetes medications or medications that may cause significant weight changes, you may need to stop them before joining the trial.

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

Research has shown that semaglutide is generally safe and effective for treating conditions like non-alcoholic fatty liver disease (NAFLD). In one study, semaglutide improved liver health and reduced inflammation in people with obesity or type 2 diabetes. Another study found semaglutide effective in treating NAFLD and safe to use.

While researchers continue to study semaglutide for young people with type 2 diabetes and fatty liver, these results suggest it is safe for similar conditions in adults. Future studies will further assess its long-term safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Semaglutide and Liraglutide because these treatments bring a unique approach to managing Type 2 Diabetes and fatty liver in youth. Unlike traditional treatments, which often involve oral medications like Metformin or lifestyle changes, Semaglutide and Liraglutide are GLP-1 receptor agonists delivered through pen injectors, offering a novel mechanism that enhances insulin secretion and reduces appetite. This approach not only targets blood sugar levels but can also contribute to weight loss, which is a crucial factor for young patients dealing with these conditions. The potential dual benefits make these treatments a promising new option in a field that has long relied on more conventional methods.

What evidence suggests that this trial's treatments could be effective for Type 2 Diabetes and Fatty Liver in youth?

Research has shown that semaglutide, which participants in this trial may receive, can improve liver health in people with Type 2 Diabetes (T2D) and Nonalcoholic Fatty Liver Disease (NAFLD). One study found that 63% of patients taking semaglutide experienced less liver inflammation without worsening liver scarring. Another study found that semaglutide reduced fat buildup and scarring while improving overall liver function. Additionally, people using semaglutide saw improvements in cholesterol, fat levels, and body mass index (BMI). These findings suggest that semaglutide may help manage liver problems and related symptoms in young people with T2D and NAFLD. ^{1 3 6 7 8}

Who Is on the Research Team?

Sonia Caprio, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for obese youths aged 10 to <21 with prediabetes or new-onset type 2 diabetes and non-alcoholic fatty liver disease. They must be in puberty, have a BMI between the 85th percentile and ≤40 kg/m², and elevated liver enzymes. Participants need to be able to self-monitor blood glucose, not pregnant or planning pregnancy without effective contraception, not on certain other medications, and generally healthy.

Inclusion Criteria

I am between 10 and 20 years old, in puberty, and if female, not pregnant.

Your ALT levels are higher than 25 units per liter.

I weigh at least 54kg.

Exclusion Criteria

You have had major depression, severe psychiatric disorders, or suicidal thoughts or behavior in the past 2 years.

Known or suspected hypersensitivity to trial product(s) or related products

I haven't had cancer, except for skin cancer or early-stage cancer, in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Semaglutide (Wegovy) or placebo for 6 months

6 months

Monthly visits (in-person)

Wash-out

Participants undergo a 3-month wash-out period after treatment

3 months

Follow-up

Participants are monitored for safety and effectiveness after the wash-out period

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Liraglutide Pen Injector
• Placebo
• Semaglutide Pen Injector

Trial Overview The study tests Semaglutide Pen Injector against a placebo in managing obesity-related complications like type 2 diabetes and fatty liver disease in young people. It aims to see if this medication can help preserve insulin-producing cell function and reduce fat in the liver.

How Is the Trial Designed?

Group I: Receive treatment Experimental Treatment 1 Intervention

Semaglutide (Wegovy) pen is a subcutaneous injection

Group II: Placebo Placebo Group 1 Intervention

The placebo pen is almost exactly the same as the Wegovy subcutaneous injection except it does not contain the active ingredient, Semaglutide.

Liraglutide Pen Injector is already approved in United States, European Union for the following indications:

Approved in United States as Saxenda for:

• Weight management in adults and children aged 12 and older

Approved in United States as Victoza for:

• Type 2 diabetes treatment in adults and children aged 10 and older
• Reducing the risk of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease

Approved in European Union as Victoza for:

• Type 2 diabetes treatment in adults and children aged 10 and older
• Reducing the risk of major cardiovascular events in adults with type 2 diabetes and established cardiovascular disease

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Liraglutide (Victoza) significantly improves glycaemic control in adults with type 2 diabetes, outperforming both placebo and other medications like rosiglitazone and insulin glargine in phase III studies.

It is generally well tolerated, with weight loss benefits and a low risk of hypoglycaemia, although gastrointestinal side effects like nausea are common but tend to decrease over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide: a review of its use in type 2 diabetes mellitus. Croom, KF., McCormack, PL.[2021]

Liraglutide, now available at a higher dose of 3.0 mg for treating obesity, has been shown to effectively control appetite and promote weight loss when combined with diet and exercise, based on results from the SCALE studies.

The drug is already established for managing type 2 diabetes at lower doses, and its mechanism of action includes effects on the endocrine pancreas and appetite regulation in the hypothalamus, indicating a dual benefit for patients with obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY]. Scheen, AJ.[2016]

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[2021]

Liraglutide, approved for Type 2 diabetes and chronic weight management, works by increasing insulin secretion and decreasing appetite, which helps promote weight loss.

Recent findings suggest that liraglutide may also protect against prediabetes and prevent bone loss by enhancing bone formation after weight loss, highlighting its broader health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide for Type 2 diabetes and obesity: a 2015 update. Iepsen, EW., Torekov, SS., Holst, JJ.[2015]

Liraglutide, a long-acting GLP-1 mimetic approved for type 2 diabetes, is administered once daily via subcutaneous injection and is effective as an add-on therapy for patients with inadequate glycaemic control.

Evidence supports liraglutide's claims of reducing weight, lowering systolic blood pressure, improving beta-cell function, and decreasing blood glucose levels, indicating its potential role in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide for type 2 diabetes? [2018]

The LEAN trial is a phase II study investigating the efficacy of liraglutide, a GLP-1 analogue, in improving liver histology in patients with non-alcoholic steatohepatitis (NASH) over 48 weeks, involving 52 participants with biopsy-confirmed NASH.

The primary outcome will assess the proportion of patients showing improvement in liver histology, specifically the disappearance of active NASH and no worsening of fibrosis, highlighting liraglutide's potential as a treatment option for this common liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide efficacy and action in non-alcoholic steatohepatitis (LEAN): study protocol for a phase II multicentre, double-blinded, randomised, controlled trial. Armstrong, MJ., Barton, D., Gaunt, P., et al.[2022]

In a subanalysis of 58 participants with type 2 diabetes and suspected non-alcoholic fatty liver disease (NAFLD), switching from other GLP-1 receptor agonists to once-weekly semaglutide significantly improved the fatty liver index (FLI), indicating better liver health.

The improvement in FLI was particularly notable for those switching from dulaglutide to semaglutide, suggesting that this treatment change could be beneficial for managing NAFLD in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Switching to Once-Weekly Semaglutide on Non-Alcoholic Fatty Liver Disease: The SWITCH-SEMA 1 Subanalysis. Nomoto, H., Takahashi, Y., Takano, Y., et al.[2023]

In a 56-week study involving 1231 participants with type 2 diabetes, semaglutide significantly reduced HbA1c levels by 1.3% and 1.6% for the 0.5 mg and 1.0 mg doses, respectively, compared to a 0.5% reduction with sitagliptin, demonstrating superior efficacy in glycaemic control.

Semaglutide also led to greater weight loss, with reductions of 4.3 kg and 6.1 kg for the two doses, compared to 1.9 kg with sitagliptin, while maintaining a similar safety profile, primarily with gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Ahrén, B., Masmiquel, L., Kumar, H., et al.[2022]

Semaglutide, a once-weekly injectable GLP-1 receptor agonist for type 2 diabetes, has shown cardiovascular benefits and a safety profile typical of its class, primarily involving gastrointestinal side effects.

While concerns about thyroid and pancreatic safety were not supported by data, there is a notable increase in diabetic retinopathy events and a modest rise in gall bladder issues, indicating the need for caution when starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of injectable semaglutide for type 2 diabetes. Peter, R., Bain, SC.[2022]

Liraglutide (Victoza) was approved by the US FDA in January 2010 as a treatment to help improve blood sugar control in adults with type 2 diabetes.

As a glucagon-like peptide 1 receptor agonist, liraglutide works by mimicking the effects of a hormone that helps regulate blood sugar levels, making it an effective option for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide. Drucker, DJ., Dritselis, A., Kirkpatrick, P.[2021]

In a phase 2 trial involving 71 patients with NASH-related cirrhosis, semaglutide did not significantly improve liver fibrosis or lead to NASH resolution compared to placebo after 48 weeks.

The safety profile of semaglutide was similar to that of the placebo, with no new safety concerns identified, and common side effects included nausea and diarrhea, but overall liver and kidney function remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Loomba, R., Abdelmalek, MF., Armstrong, MJ., et al.[2023]

Liraglutide, a GLP-1 analogue, has shown safety and efficacy in treating two adolescent females with type II diabetes and biopsy-proven nonalcoholic steatohepatitis (NASH), leading to weight loss and improved liver enzymes.

This case series suggests that liraglutide could be a beneficial treatment option for pediatric patients with obesity, NAFLD, and T2DM, especially when lifestyle interventions are ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide with Lifestyle Intervention in Adolescents with Overweight/Obesity, Nonalcoholic Fatty Liver Disease, and Type II Diabetes Mellitus. Kohut, T., Panganiban, J.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2413258

Phase 3 Trial of Semaglutide in Metabolic Dysfunction– ... A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of the patients in the semaglutide group and in 22.4% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11354027/

Therapeutic Effects of Semaglutide on Nonalcoholic Fatty ... Semaglutide improves lipid profile, liver steatosis, and fibrosis parameters and reduces the BMI in T2D and obese patients with NAFLD.

3. mcvfoundation.org mcvfoundation.org/news/stories/reversing-liver-damage

Reversing Liver Damage | Medical College of Virginia ... About 63% of semaglutide users experienced a reduction in liver inflammation without worsening scarring, compared to only 34% of the placebo ...

4. fda.gov fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash

FDA Approves Treatment for Serious Liver Disease Known ... Interim results showed 63% of participants receiving Wegovy had MASH resolution and no worsening of liver scarring compared to 34% of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06983171

Study Details | NCT06983171 | Semaglutide Effectiveness ... - Semaglutide may help by: Reducing liver fat and inflammation. Improving weight, blood sugar, and cholesterol. Slowing liver fibrosis progression. Study ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10600803/

Efficacy and safety of semaglutide in non-alcoholic fatty liver ... Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile. Future studies are required to evaluate its effects.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6617813/

Effect of semaglutide on liver enzymes and markers of ... Conclusions. Semaglutide significantly reduced ALT and hsCRP in clinical trials in subjects with obesity and/or type 2 diabetes. 1. INTRODUCTION.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1871402123001455

Role of semaglutide in the treatment of nonalcoholic fatty ... Treatment with 24 weeks of semaglutide could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters in patients with ...