Lilly's Most Potent Weight Loss Drug Yet Could Help Manage Fatty Liver Disease, Too

Key Takeaways

The latest innovation in diabetes and obesity drugs is slated to be not only more effective than major players like Ozempic and Mounjaro at promoting weight loss and improving glycemic control, but also at reducing fat in the liver.

This is a key step for preventing the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease.

Manufacturer Eli Lilly shared data fromtwo phase 2 clinical trials in patients with type 2 diabetes and those with overweight or obesity at the American Diabetes Association meeting last month.

The early data indicates that when administered at the highest dosage, the drug, called retatrutide, can cause weight loss of 24% over 11 months. If additional studies support these findings, retatrutide could become the most potent weight loss medication on the market.

The company also tested the drug on a small subset of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). The drug normalized liver fat in 9 of 10 patients taking the two highest doses of retatrutide, suggesting it could “has the potential to resolve” MASLD.

More Effective Than Mounjaro

In its clinical trial, Lilly tested how well six different doses of retatrutide worked compared to a placebo.

The study included 338 adults with obesity or overweight. After 24 weeks, the people who received 12 milligrams of retatrutide—the highest dosage—saw up to 17.5% weight loss. After 48 weeks, the group saw 24.2% average weight loss.

Even at 1 milligram—the lowest dosage tested—participants sawa weight reduction of 7% at 24 weeks and almost 9% at 48 weeks.Major medical organizations say most people need to lose about 5% to 10% of their weight within six months to see improvements in major outcomes, including blood pressure, cholesterol levels, and likelihood of pre-diabetes progression.

Those numbers put retatrutide on track to overtake its predecessors. By comparison, Mounjaro can help patients lose nearly 16% of their body weight.

Mounjaro Generic May Soon Join Wegovy as a Weight Loss-Approved Drug

An Ozempic 3.0?

The class of powerful new obesity and diabetes drugs that includes Wegovy and Ozempic are called GLP-1 agonists. That’s because the drugs mimic a hormone called glucagon-like peptide 1. When there is food in the stomach, the extra GLP-1 stimulates the pancreas to create more insulin. That helps to lower blood sugar and delays digestion and appetite, making people feel full longer.

Mounjaro is a dual agonist, meaning it acts on both GLP-1 and gastric inhibitory polypeptide (GIP). Phase 3 trials have proven Mounjaro to be even better at lowering blood sugar and reducing weight than Ozempic and other drugs that act on GLP-1 alone.

Retatrutide is considered a “tri-agonist” because it acts on one additional hormone called glucagon.

Glucagon can stimulate glucose production, so scientists haven’t historically considered it a diabetes treatment, saidSubbulaxmi Trikudanathan, MD, MRCP, MMSc,clinical associate professor and Medical Director of the University of Washington Diabetes Institute.

But data from humans and animals over the past several decades indicate that it can reduce food intake when paired with a GLP-1 agonist, while also increasing resting energy expenditure. Glucagon also appears to break down fatty acids in the liver, with positive effects for people with MASLD.

“The dual agonist is better than the single and then the triple is better than dual,” Trikudanathan said. “The glucagon is complementing the other two incretin hormones in enhancing its weight loss effects and also having some independent effects in the liver.”

Ways to Save on Mounjaro and Ozempic

A Potential New Treatment for Fatty Liver Disease

The results of studies on the liver health benefits of other highly effective weight loss drugs are mixed.

One study showed that 59% of people taking semaglutide—sold as Ozempic and Wegovy—saw a resolution of a severe form of MASLD called metabolic dysfunction-associated steatohepatitis (MASH), the condition formerly known as nonalcoholic steatohepatitis (NASH).But the drug didn’t appear to significantly help people who have already developed scarring.

What Is Fatty Liver Disease?

Eli Lilly studied retatrutide only in people in the early stages of liver disease. As MASH—which is commonly associated with obesity and diabetes—develops, some people experience fibrosis, or scarring of the liver,hardening of the liver, and inflammation of the fat cells.

GLP-1 agonists appear can be helpful in reducing liver fat for people in the early stages of MASLD or in MASH. However, it’s not yet clear whether the drugs will meaningfully improve outcomes for people with fibrosis.

Trikudanathan said the next steps are to study retatrutide in a larger trial and to analyze how the drug affects liver tissue at a microscopic level.

“Obesity is on the rise, so it is important to reduce hepatic fat at the earliest,” Trikudanathan said. “This is all promising, but we’d like to see more histology data and liver biopsies, and what does it do if someone’s already established fibrosis?”

What This Means For YouEli Lilly is still testing retatrutide in clinical trials and likely won’t apply for FDA approval for many months. In the meantime, there are several GLP-1-based drugs on the market for obesity and diabetes treatment. If you’re seeking treatment for one of those conditions or for fatty liver disease, speak with a health provider about your treatment options.

What This Means For You

Eli Lilly is still testing retatrutide in clinical trials and likely won’t apply for FDA approval for many months. In the meantime, there are several GLP-1-based drugs on the market for obesity and diabetes treatment. If you’re seeking treatment for one of those conditions or for fatty liver disease, speak with a health provider about your treatment options.

6 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Jastreboff AM, Kaplan LM, Frías JP, et al.Triple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial.N Engl J Med. Published online June 26, 2023. doi:10.1056/NEJMoa2301972American Diabetes Association.American Diabetes Association highlights novel agent retatrutide which results in substantial weight reduction in people with obesity or type 2 diabetes during late breaking symposium.Cornier MA.A review of current guidelines for the treatment of obesity.Am J Manag Care. 2022;28(Suppl 15):S288-S296. doi:10.37765/ajmc.2022.89292Eli Lilly and Company.Lilly’s tirzepatide achieved up to 15.7% weight loss in adults with obesity or overweight and type 2 diabetes in SURMOUNT-2.Hayashi Y.Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver.J Diabetes Investig. 2021;12(1):32-34. doi:10.1111/jdi.13315Newsome PN, Buchholtz K, Cusi K, et al.A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.N Engl J Med. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395

6 Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Jastreboff AM, Kaplan LM, Frías JP, et al.Triple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial.N Engl J Med. Published online June 26, 2023. doi:10.1056/NEJMoa2301972American Diabetes Association.American Diabetes Association highlights novel agent retatrutide which results in substantial weight reduction in people with obesity or type 2 diabetes during late breaking symposium.Cornier MA.A review of current guidelines for the treatment of obesity.Am J Manag Care. 2022;28(Suppl 15):S288-S296. doi:10.37765/ajmc.2022.89292Eli Lilly and Company.Lilly’s tirzepatide achieved up to 15.7% weight loss in adults with obesity or overweight and type 2 diabetes in SURMOUNT-2.Hayashi Y.Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver.J Diabetes Investig. 2021;12(1):32-34. doi:10.1111/jdi.13315Newsome PN, Buchholtz K, Cusi K, et al.A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.N Engl J Med. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Jastreboff AM, Kaplan LM, Frías JP, et al.Triple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial.N Engl J Med. Published online June 26, 2023. doi:10.1056/NEJMoa2301972American Diabetes Association.American Diabetes Association highlights novel agent retatrutide which results in substantial weight reduction in people with obesity or type 2 diabetes during late breaking symposium.Cornier MA.A review of current guidelines for the treatment of obesity.Am J Manag Care. 2022;28(Suppl 15):S288-S296. doi:10.37765/ajmc.2022.89292Eli Lilly and Company.Lilly’s tirzepatide achieved up to 15.7% weight loss in adults with obesity or overweight and type 2 diabetes in SURMOUNT-2.Hayashi Y.Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver.J Diabetes Investig. 2021;12(1):32-34. doi:10.1111/jdi.13315Newsome PN, Buchholtz K, Cusi K, et al.A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.N Engl J Med. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395

Jastreboff AM, Kaplan LM, Frías JP, et al.Triple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial.N Engl J Med. Published online June 26, 2023. doi:10.1056/NEJMoa2301972

American Diabetes Association.American Diabetes Association highlights novel agent retatrutide which results in substantial weight reduction in people with obesity or type 2 diabetes during late breaking symposium.

Cornier MA.A review of current guidelines for the treatment of obesity.Am J Manag Care. 2022;28(Suppl 15):S288-S296. doi:10.37765/ajmc.2022.89292

Eli Lilly and Company.Lilly’s tirzepatide achieved up to 15.7% weight loss in adults with obesity or overweight and type 2 diabetes in SURMOUNT-2.

Hayashi Y.Glucagon regulates lipolysis and fatty acid oxidation through inositol triphosphate receptor 1 in the liver.J Diabetes Investig. 2021;12(1):32-34. doi:10.1111/jdi.13315

Newsome PN, Buchholtz K, Cusi K, et al.A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis.N Engl J Med. 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395

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