This study is researching a condition called Metabolic Dysfunction-Associated Steatotic Liver Disease, which is a condition where excess fat builds up in the liver and can lead to liver scarring and damage over time. The study will test several different medications to see if they can help prevent serious liver problems from developing. The medications being studied include tirzepatide (also known by its code name LY3298176), which is given as an injection using a pre-filled pen, and retatrutide (also known as LY3437943), which is also given as an injection. Some participants will receive placebo instead of active medication. All study medications are given by injection under the skin.

The purpose of this study is to find out whether the study medications are better than placebo at reducing the occurrence of major liver-related complications. During the study, researchers will monitor participants for various liver problems including progression to cirrhosis (severe liver scarring), development of complications like varices (enlarged veins in the digestive tract), ascites (fluid buildup in the abdomen), hepatic encephalopathy (brain function problems caused by liver disease), and other serious liver conditions. The study will also track whether participants need liver transplantation or experience other serious outcomes.

Participants in this study will receive their assigned treatment over an extended period while being regularly monitored by the study team. The study requires participants to have evidence of liver fat confirmed by MRI (a type of imaging scan) and liver scarring confirmed through non-invasive tests, though a liver biopsy is not required to join the study. Throughout the study, participants will have regular check-ups and assessments to evaluate how well the treatment is working and to monitor their liver health and overall wellbeing.