DAY 2: Resmetirom Benefit Extends Beyond Resolution of Steatohepatitis in People with Type 2 Diabetes

Patients with type 2 diabetes mellitus who were treated with resmetirom for metabolic dysfunction-associated steatotic liver disease (MASLD) experienced significant improvements in lipid profiles and liver enzymes, according to a multicenter propensity-matched analysis.

Lead author Regis Lee, DO, an internal medicine specialist at the HCA Healthcare Riverside Community Hospital in Riverside, California, noted that patients with diabetes achieved greater improvements compared with their counterparts without diabetes, reflecting potentially distinct metabolic and hepatic responses to resmetirom in this population. Lee presented the results of the analysis at the 2025 Annual Scientific Meeting of the American College of Gastroenterology in Phoenix, Arizona.

MASLD is a prevalent chronic liver disease that has a bidirectional relationship with type 2 diabetes. While diabetes has been identified as a driver of MASLD, steatotic liver disease can worsen the course and prognosis of diabetes. Without treatment, MASLD can progress to severe conditions such as cirrhosis and hepatocellular carcinoma, which carry a high risk of mortality. 
Resmetirom, a selective agonist of thyroid hormone receptor beta (THR-β), was the first therapy approved specifically for adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), with moderate-to-advanced liver fibrosis (stages F2 and F3). Resmetirom has demonstrated various benefits, including a reduction in liver fat, improvements in liver enzymes, and MASH resolution. Moreover, phase 2 and 3 clinical trials consistently showed that resmetirom can significantly improve lipid profiles in patients with MASH.

Lee and colleagues designed a study to compare the impact of resmetriom on hepatic enzymes and lipid profiles in patients with MASLD and MASH with and without diabetes. Using the TriNetX database of 148 healthcare organizations, the authors identified patients with and without diabetes who were prescribed resmetirom. After propensity score matching for age, race, gender, BMI, and lipid-lowering agents, 461 patients were included in each group. The authors then compared mean laboratory values between the two cohorts at the initiation of treatment and at 1 month, 6 months, and 12 months after starting resmetirom.

The results illustrated distinct lipid trajectories for patients with diabetes compared to their non-diabetic counterparts. Patients with diabetes treated with resmetirom had statistically lower low-density lipoprotein (LDL) cholesterol levels and total cholesterol levels at all follow-up timepoints in the study. However, high-density lipoprotein (HDL) cholesterol levels were not significantly different between the two groups at each follow-up time point, and triglyceride levels were statistically different between the cohorts only at the 1-month mark. Liver enzymes, specifically alanine transaminase (ALT) and aspartate transaminase (AST), also followed distinct trajectories. Although both groups experienced improvements in liver enzymes by 6 and 12 months, the results showed a statistically significant difference between the cohorts only in AST levels and only at 6 months. Gamma-glutamyl transferase (GGT) levels declined in both groups over 12 months, however, the greater reduction experienced by patients with diabetes was not statistically significant at each follow-up.

“Overall, the study highlights distinct biochemical response patterns to resmetirom among MASLD and MASH patients based on diabetic status,” Lee said. “Diabetic patients demonstrated more stable liver enzymes and sustained lipid reductions over 12 months. Future research should explore whether underlying glycemic control, insulin resistance, or antidiabetic therapies modulate resmetirom's efficacy and can lead to long-term improved outcomes.” The findings suggest that individuals with diabetes and steatotic liver disease can derive the greatest benefit from resmetirom therapy, underscoring the potential for diabetes-specific treatment strategies in MASLD and MASH.