A recent retrospective study at Children’s Hospital of Philadelphia (CHOP) showed that glucagon-like peptide-1 (GLP-1) receptor agonists significantly reduced alanine aminotransferase (ALT) in children with metabolic dysfunction-associated steatotic liver disease (MASLD) – particularly in those who also had type 2 diabetes.
Previously known as non-alcoholic fatty liver disease (NAFLD), MASLD is now the most common chronic liver disease in children – affecting about 10% of U.S. children – and is rapidly becoming the leading cause of liver transplant in adults.
Gold standard of care
Lifestyle modifications, such as eating a healthy diet and increasing exercise, remain the first line of treatment and the gold standard for treating MASLD in pediatrics. However, with growing rates of obesity and type 2 diabetes (T2DM) accompanying pediatric MASLD, lifestyle changes are often difficult to consistently implement in clinical practice.
While there are currently no FDA-approved treatments for pediatric MASLD, GLP-1 receptor agonists (GLP1-RAs) are being used in patients with MASLD with obesity and/or T2DM, and prescribed with the FDA indication of weight management/diabetes. These medications include a variety of GLP-1 RAs such as semaglutide (Wegovy® and Ozempic®), dulaglutide (Trulicy®), liraglutide (Victoza®), and exenatide (Bydureon®). At CHOP, these are being prescribed by Health and Well-being Clinic providers, endocrinologists and gastroenterologists.
Seeking answers in real-world setting
With the leadership of Jennifer Panganiban, MD, attending gastroenterologist and director of CHOP’s Metabolic Dysfunction-Associated Steatotic Liver Disease Program, we conducted a retrospective cohort study to investigate the efficacy of GLP-1RAs to treat MASLD in a real-world setting. Our single-center, IRB-approved study included a chart review of patients 21 and younger who started treatment with GLP-1RAs at CHOP for either an indication of obesity or diabetes between Jan. 1, 2018, and Jan. 10, 2024.
Our cohort included 111 patients:
- 51% male, 49% female
- 39% white, 34% Black, and 15% Hispanic
- Had a median baseline alanine aminotransferase (ALT) of 78.1 U/L
- Had a median BMI of 43 kg/m²
- Underwent an average treatment duration of 13 months
- Were prescribed the following GLP-1RAs:
- semaglutide (41%)
- liraglutide (37%)
- dulaglutide (19%)
- exenatide (3%)
We collected labs at baseline, 6 months into treatment, and post-therapy, along with demographic data, medication dosing information, imaging studies, biopsy results and side effects.
Study results
The study’s primary outcome was a reduction in ALT of at least 17 U/L, deemed to be associated with histologic improvement of steatohepatitis based on current American Association for the Study of Liver Disease guidelines.
Secondary outcomes included changes in other MASLD-associated biomarkers including BMI, BMI percentiles, BMI z-score, aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) levels, glycated hemoglobin (HbA1c), platelet counts, 25-hydroxy vitamin D and cholesterol levels, as well as blood pressure measurements.
Results from our study showed ALT improvement by 23 U/L after 6 months of treatment and by 18 U/L when therapy concluded. Results were more significant in patients with a higher baseline ALT (>2x the upper limit of normal), which decreased by ~47 U/L. Stratifying patients further by prescribed indication, there was a greater mean reduction in ALT by ~33 U/L in patients prescribed a GLP-1RAs for diabetes. There were no clinically significant changes in BMI, BMI percentile or BMI z-score, but improvements in HbA1c, AST, GGT and triglycerides were seen.
GLP-1 RAs are therefore a potentially powerful option for our pediatric patients with MASLD in conjunction with lifestyle changes, especially for patients with T2DM, who have the highest risk for progression if left untreated. As there are currently no approved medications for the treatment of pediatric MASLD, this study provides insight into a promising therapeutic approach for this condition in conjunction with lifestyle modifications. Our results provide a strong starting point for future investigations and highlight the need for continued exploration of GLP-1RAs in pediatric MASLD.
Andrea M. Tou, MBBCh, is a fellow with the Division of Gastroenterology, Hepatology and Nutrition at Children’s Hospital of Philadelphia.
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A recent retrospective study at Children’s Hospital of Philadelphia (CHOP) showed that glucagon-like peptide-1 (GLP-1) receptor agonists significantly reduced alanine aminotransferase (ALT) in children with metabolic dysfunction-associated steatotic liver disease (MASLD) – particularly in those who also had type 2 diabetes.
Previously known as non-alcoholic fatty liver disease (NAFLD), MASLD is now the most common chronic liver disease in children – affecting about 10% of U.S. children – and is rapidly becoming the leading cause of liver transplant in adults.
Gold standard of care
Lifestyle modifications, such as eating a healthy diet and increasing exercise, remain the first line of treatment and the gold standard for treating MASLD in pediatrics. However, with growing rates of obesity and type 2 diabetes (T2DM) accompanying pediatric MASLD, lifestyle changes are often difficult to consistently implement in clinical practice.
While there are currently no FDA-approved treatments for pediatric MASLD, GLP-1 receptor agonists (GLP1-RAs) are being used in patients with MASLD with obesity and/or T2DM, and prescribed with the FDA indication of weight management/diabetes. These medications include a variety of GLP-1 RAs such as semaglutide (Wegovy® and Ozempic®), dulaglutide (Trulicy®), liraglutide (Victoza®), and exenatide (Bydureon®). At CHOP, these are being prescribed by Health and Well-being Clinic providers, endocrinologists and gastroenterologists.
Seeking answers in real-world setting
With the leadership of Jennifer Panganiban, MD, attending gastroenterologist and director of CHOP’s Metabolic Dysfunction-Associated Steatotic Liver Disease Program, we conducted a retrospective cohort study to investigate the efficacy of GLP-1RAs to treat MASLD in a real-world setting. Our single-center, IRB-approved study included a chart review of patients 21 and younger who started treatment with GLP-1RAs at CHOP for either an indication of obesity or diabetes between Jan. 1, 2018, and Jan. 10, 2024.
Our cohort included 111 patients:
- 51% male, 49% female
- 39% white, 34% Black, and 15% Hispanic
- Had a median baseline alanine aminotransferase (ALT) of 78.1 U/L
- Had a median BMI of 43 kg/m²
- Underwent an average treatment duration of 13 months
- Were prescribed the following GLP-1RAs:
- semaglutide (41%)
- liraglutide (37%)
- dulaglutide (19%)
- exenatide (3%)
We collected labs at baseline, 6 months into treatment, and post-therapy, along with demographic data, medication dosing information, imaging studies, biopsy results and side effects.
Study results
The study’s primary outcome was a reduction in ALT of at least 17 U/L, deemed to be associated with histologic improvement of steatohepatitis based on current American Association for the Study of Liver Disease guidelines.
Secondary outcomes included changes in other MASLD-associated biomarkers including BMI, BMI percentiles, BMI z-score, aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) levels, glycated hemoglobin (HbA1c), platelet counts, 25-hydroxy vitamin D and cholesterol levels, as well as blood pressure measurements.
Results from our study showed ALT improvement by 23 U/L after 6 months of treatment and by 18 U/L when therapy concluded. Results were more significant in patients with a higher baseline ALT (>2x the upper limit of normal), which decreased by ~47 U/L. Stratifying patients further by prescribed indication, there was a greater mean reduction in ALT by ~33 U/L in patients prescribed a GLP-1RAs for diabetes. There were no clinically significant changes in BMI, BMI percentile or BMI z-score, but improvements in HbA1c, AST, GGT and triglycerides were seen.
GLP-1 RAs are therefore a potentially powerful option for our pediatric patients with MASLD in conjunction with lifestyle changes, especially for patients with T2DM, who have the highest risk for progression if left untreated. As there are currently no approved medications for the treatment of pediatric MASLD, this study provides insight into a promising therapeutic approach for this condition in conjunction with lifestyle modifications. Our results provide a strong starting point for future investigations and highlight the need for continued exploration of GLP-1RAs in pediatric MASLD.
Andrea M. Tou, MBBCh, is a fellow with the Division of Gastroenterology, Hepatology and Nutrition at Children’s Hospital of Philadelphia.
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