Semaglutide for Preventing Weight Gain After Liver Transplant

Overseen By Mohammad S Siddiqui, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must not be taking: GLP-1RA, SGLT-2 inhibitors

Disqualifiers: BMI ≤ 27, GFR ≤ 25, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 72 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, semaglutide will be compared to placebo (a look-alike inactive substance, a "sugar pill") to determine if its use will prevent weight gain after liver transplantation (LT). In addition, researchers will be testing to determine if semaglutide prevents the development of Non-Alcoholic Fatty Liver Disease (NAFLD) after transplant through Magnetic Resonance Imaging (MRI) and laboratory results.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain diabetes medications like GLP-1 receptor agonists or SGLT-2 inhibitors when you start the trial.

What data supports the effectiveness of the drug semaglutide for preventing weight gain after liver transplant?

Research shows that semaglutide is effective in helping people with obesity lose weight and is safe for those with liver issues. This suggests it might help prevent weight gain after a liver transplant. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide has been studied for safety in various conditions, including obesity and liver issues, and no major safety concerns have been identified. Reported side effects are similar to those seen with other medications in its class, and it is generally well-tolerated even in people with liver problems. ^{2 3 5 6 7}

How is the drug semaglutide unique for preventing weight gain after liver transplant?

Semaglutide is unique because it is a glucagon-like peptide-1 (GLP-1) analogue that can be administered orally or via injection, and it has been shown to be effective in managing weight in people with obesity and those with liver conditions like non-alcoholic steatohepatitis (NASH). This makes it a novel option for preventing weight gain after liver transplant, as there are no standard treatments specifically for this condition. ^{2 3 5 7 8}

Research Team

Mohammad S Siddiqui, MD

Principal Investigator

Virginia Commonwealth University

Eligibility Criteria

This trial is for adults aged 18-75 who've had a liver transplant within the last 8-24 weeks. Participants may have diabetes or pre-diabetes, must be able to eat normally, and women must not be pregnant or breastfeeding. Exclusions include those with certain medical conditions like gastroparesis, pancreatitis, specific cancers, severe kidney issues, or uncontrolled diabetic eye problems.

Inclusion Criteria

Ability to provide informed consent

I had a liver transplant surgery 2 to 6 months ago.

My liver transplant is functioning well, according to my doctor.

Exclusion Criteria

I have had cancer after a liver transplant, but not skin cancer.

I am experiencing acute cellular rejection.

You have had an allergic reaction to semaglutide or any of its ingredients.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive semaglutide or placebo subcutaneously once weekly with a 20-week dose escalation period followed by 52 weeks at the maximum tolerated dose

72 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Semaglutide

Trial Overview Researchers are testing if Semaglutide can prevent weight gain and the return of Non-Alcoholic Fatty Liver Disease after liver transplantation by comparing it to a placebo. The study involves monitoring through MRI scans and lab tests to assess effectiveness.

Participant Groups

Group I: Semaglutide Experimental Treatment 1 Intervention

Semaglutide administered subcutaneously (under the skin) once weekly. There will be a 20 week lead in period of dose escalation before reaching the target dose of 2.4mg weekly. Semaglutide will then be administered at the maximum tolerated dose for 52 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo administered subcutaneously (under the skin) once weekly.

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Novo Nordisk A/S

Industry Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

In a study involving 38 participants with type 2 diabetes, semaglutide did not significantly alter the glucagon response during hypoglycemia compared to placebo, indicating it maintains normal counterregulatory hormone function.

Participants treated with semaglutide experienced a lower increase in noradrenaline and cortisol during hypoglycemia, and reported fewer hypoglycemic symptoms, suggesting a potentially safer profile without compromising cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of once-weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo-controlled, double-blind, crossover trial. Korsatko, S., Jensen, L., Brunner, M., et al.[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]

In a phase 3 trial involving 667 adults with overweight or obesity, oral semaglutide 50 mg taken daily resulted in a significant average weight loss of 15.1% compared to only 2.4% with placebo over 68 weeks, demonstrating its efficacy in weight management.

While semaglutide was effective, it was associated with a higher incidence of adverse events, particularly gastrointestinal issues, affecting 80% of participants, indicating that while it is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Knop, FK., Aroda, VR., do Vale, RD., et al.[2023]

In a phase IIa study involving 145 participants with non-alcoholic fatty liver disease (NAFLD), efinopegdutide (10 mg weekly) resulted in a significantly greater reduction in liver fat content (LFC) compared to semaglutide (1 mg weekly), with reductions of 72.7% and 42.3% respectively after 24 weeks (p < 0.001).

Both treatments led to weight loss, with efinopegdutide showing an 8.5% reduction compared to 7.1% for semaglutide, although efinopegdutide was associated with slightly higher gastrointestinal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. Romero-Gómez, M., Lawitz, E., Shankar, RR., et al.[2023]

A clinical trial involving 56 subjects with varying degrees of hepatic impairment found that oral semaglutide's pharmacokinetics were similar across all groups, indicating that liver function does not significantly affect how the drug is absorbed and processed in the body.

No safety concerns were identified for patients with hepatic impairment taking semaglutide, suggesting that dose adjustments are unnecessary for these patients, as adverse events were consistent with those seen in other similar medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Tolerability of Oral Semaglutide in Subjects With Hepatic Impairment. Baekdal, TA., Thomsen, M., Kupčová, V., et al.[2019]

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

The STEP program is a comprehensive study involving approximately 5,000 participants to evaluate the efficacy and safety of semaglutide 2.4 mg for weight management in adults with obesity or overweight, with results expected in 2020/2021.

The trials will assess weight loss outcomes and tolerability in diverse populations, including those with and without type 2 diabetes, providing valuable insights into long-term weight management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Kushner, RF., Calanna, S., Davies, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of once-weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo-controlled, double-blind, crossover trial. [2021]

2. Netherlands 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. [2023]

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

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Tolerability of Oral Semaglutide in Subjects With Hepatic Impairment. [2019]

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

Semaglutide for the treatment of obesity. [2023]

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

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. [2022]

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

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. [2021]