Retatrutide, Weight Loss Injections and Fatty Liver Disease
Could retatrutide, an experimental weight loss drug, promote liver health?
Interest in drugs like Ozempic and Wegovy for weight loss has grown rapidly over the past several years, with 6% of U.S. adults admitting to current or prior use. (1) While losing weight can improve health overall, the use of weight loss injections may also help combat fatty liver disease. (2) One such medication researchers are experimenting with is called retatrutide.
What is Retatrutide?
Retatrutide is a triple receptor agonist, affecting three hormones related to obesity: (3)
- Glucose-dependent insulinotropic polypeptide (GIP)
- Glucagon-like peptide 1 (GLP-1)
- Glucagon (GCG)
Receptor agonists interact with receptors like natural substances, causing a biological response. Oftentimes, the response it causes has positive effects. (4)
How Retatrutide Works
GIP and GLP-1 are both produced in the intestines. GIP promotes the deposit of fat in body tissues while GLP-1 affects appetite and the way food moves through the digestive tract. (5) Glucagon is produced in the pancreas and increases blood glucose levels. It affects how the body metabolizes fat. (6)
By influencing the receptors of each of these hormones, retatrutide can influence how the body deposits and metabolizes fats, also impacting appetite and digestion. Together, this can help people lose weight.
It can also help improve liver health, with one study finding that losing 10% or more of your body weight can help reduce, reverse, or — in some cases — even resolve nonalcoholic fatty liver disease. (7)
Retatrutide, Obesity, and Liver Health: The Research
Researchers continue to try to learn more about retatrutide and its effects, with many studies having promising findings.
One was a Phase 2 trial — which is used to evaluate a drug’s safety and effectiveness for a specific condition — and its results were published in The New England Journal of Medicine. (3)
Some of the 338 participants (all with obesity) were given varying doses of retatrutide while the control group received a placebo or sham treatment.
- After 24 weeks, the active drug group lost between 7.2% and 17.5% of their body weight (depending on dose), compared to a 1.6% loss in the placebo group.
- After 48 weeks, weight loss in the retatrutide group increased to between 8.7% and 24.2% of participants’ body weight, compared to a 2.1% loss in the control.
In a meeting of the American Association for the Study of Liver Diseases, Dr. Arun Sanyal, the director of Virginia Commonwealth University’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, shared the study findings, adding that participants also had reductions in their liver fat. Dr. Sanyal reported that more than 85% of subjects with fatty liver disease lowered their liver fat so much with retatrutide that they would no longer be classified as having the disease. (8)
What Could This Mean for People with Liver Disease?
Currently, there is only one drug approved by the U.S. Food and Drug Administration to treat fatty liver disease: resmetirom. Sold under the brand name Rezdiffra, this medication was approved on March 14, 2024, for the treatment of nonalcoholic steatohepatitis or NASH (since renamed to metabolic dysfunction-associated steatohepatitis or MASH) with moderate to advanced liver scarring. (9)
If more research finds that retatrutide is both effective and safe for the treatment of fatty liver disease, this may provide another drug-based treatment option in the future. The drug could potentially be an option for people who don’t respond well to resmetirom.
Depending on what research reveals, it may also have different levels of safety and effectiveness or be beneficial for certain liver conditions.
Potential Retatrutide Side Effects
Speaking of drug safety, the most common adverse side effects noted in the Phase 2 trial were gastrointestinal. Starting with a lower dose helped ease these effects, which were often mild to moderate in severity. Some participants taking the higher doses had peak heart rate increases at the 24-week mark, but these rates declined as the study progressed.
Where to Go from Here
The FDA warns that some companies are currently selling drugs containing retatrutide, even though it has not yet been approved. (10) This means that it hasn’t been deemed safe or effective, and there is no assurance that the drug received meets current quality standards.
Until such time that it is approved, if ever, your healthcare provider can help determine whether medication, lifestyle changes, or over-the-counter liver support supplements may help support your liver health.
(1) Gallup. (2024, May 21). Injectable Weight Loss Drugs: Who Uses Them, and Do They Work? Retrieved April 09, 2025, from https://news.gallup.com/poll/644861/injectable-weight-loss-drugs-uses-work.aspx
(2) Tompa, R. (September 17, 2024). Fatty Liver Disease: The Process Behind the Benefit of Weight Loss Drugs. Yale School of Medicine. Retrieved April 09, 2025, from https://medicine.yale.edu/news-article/fatty-liver-disease-the-process-behind-the-benefit-of-weight-loss-drugs/
(3) Jastreboff, A.M., Kaplan, L.M., Frias, J.P., et al. (2023, June 26). The New England Journal of Medicine. doi:10.1056/NEJMoa2301972
(4) Sigma-Aldrich. (n.d.). Receptor Agonists and Antagonists. Retrieved April 09, 2025, from https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/protein-biology/interrogation-protein-pathways/receptor-agonists-antagonists
(5) Seino, Y., Yamazaki, J. (2022, May 11). Roles of Glucose-Dependent Insulinotropic Polypeptide in Diet-Induced Obesity. Journal of Diabetes Investigation. doi:10.1111/jdi.13816
(6) Scott, R.V., Bloom, S.R. (2018, February). Problem or Solution: The Strange Story of Glucagon. Peptides. PMID:29412829
(7) Vilar-Gomez, E., Martinez-Perez, Y., Calzadilla-Bertot, L., et al. (2015, August). Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. doi:10.1053/j.gastro.2015.04.005
(8) Hostetler, A.J. (2023, November 13). Retatrutide ‘Wiped Out’ Fat in Liver of Obese Patients: Potential Drug to Treat Obesity May Someday Help Some People Avoid Liver Disease, VCU Research Says. VCU Health. Retrieved April 09, 2025, from https://www.vcuhealth.org/news/retatrutide-wiped-out-fat-in-liver-of-obese-patients/
(9) U.S. Food and Drug Administration. (2024, March 14). FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. Retrieved April 09, 2025, from https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease
(10) U.S. Food and Drug Administration. (2025, March 17). FDA’s Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. Retrieved April 09, 2025, from https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss
About the Author
Christina M. DeBusk, BS is an accomplished health writer and editor with a passion for natural wellness, disease prevention, and holistic treatment options. With certifications as a Nutrition Specialist, Personal Trainer, and Transformation Specialist, Christina brings a wealth of expertise to her writing. Her articles have been featured in numerous health-related publications both online and in print including Woman’s Day, Massage Magazine, Country Living, Chiropractic Economics, and Very Well Mind, empowering readers to lead healthier lives through informed choices and natural solutions.
