Magnetic resonance imaging (MRI) findings from a new phase 3 study suggest that survodutide, a glucagon receptor/glucagon-like peptide-1 receptor dual agonist, may facilitate a significant reduction of liver fat in obese patients with at-risk metabolic dysfunction-associated steatotic liver disease (MASLD).
For the randomized, double-blind, placebo-controlled phase 3 trial, recently published in Nature Medicine, researchers reviewed data from 216 patients who had hepatic steatosis and liver inflammation or fibrosis or metabolic dysfunction-associated steatohepatitis (MASH) within the last three years. The study authors noted the mean baseline liver fat content (LFC) was 16.9 percent, according to MRI-proton density fat fraction (MRI-PDFF) assessments.
Over a 48-week evaluation period, the researchers found that survodutide had a significant impact in reducing LFC as per MRI-PDFF evaluations.
• According to the study, 84.2 percent of patients treated with survodutide achieved > 30 percent reduction in LFC in comparison to 24.3 percent of placebo-control patients.
• The study authors pointed out a 66 percent difference between the survodutide-treated group and the placebo cohort for a > 50 percent reduction in LFC (75.3 percent vs. 8.6 percent).
• Over 52 percent more patients in the survodutide-treated cohort had a > 70 percent LFC reduction in contrast to the placebo group (55.5 percent vs. 2.5 percent), according to the researchers.
“A relative reduction of ≥30% in MRI-PDFF-assessed LFC has been shown to be associated with a higher likelihood of histologic improvement and MASH resolution, and, for people with MASH and fibrosis stage F2–F3, a ≥50% reduction in LFC has correlated with fibrosis regression. In the present trial, a substantial proportion of participants experienced these levels of reduction in MRI-PDFF-assessed LFC with survodutide,” noted lead study author Lee M. Kaplan, MD, the director of the Obesity and Metabolism Institute in Boston and Chair of the Obesity Medicine Fellowship Council in Rockville, Md., and colleagues.
Survodutide treatment also led to a mean 12.2 percent reduction in body weight in comparison to one percent in the placebo group, according to the study.
In regard to the safety profile of survodutide, the researchers said the most common adverse events were gastrointestinal in nature and were mild to moderate in severity.
Three Key Takeaways
- Survodutide demonstrates robust liver fat reduction in at-risk MASLD. In this phase 3 RCT, 84.2 percent of survodutide-treated patients achieved > 30 percent reduction in liver fat content (LFC) via MRI-PDFF, compared to only 24.3 percent in the placebo group — a threshold associated with histologic improvement and MASH resolution.
- Deeper reductions in LFC suggest potential for fibrosis regression. Over 75 percent of survodutide-treated patients achieved > 50 percent LFC reduction (vs. 8.6 percent placebo), a level correlated with fibrosis regression in MASH patients with F2–F3 staging, pointing to meaningful structural liver benefit beyond fat reduction alone.
- Clinically meaningful weight loss accompanied hepatic benefits with a manageable safety profile. Survodutide produced a mean 12.2 percent body weight reduction (vs. 1 percent with placebo), and adverse events were predominantly mild to moderate GI effects.
While cautioning that further research is necessary to gain more clarity into the mechanisms of action for survodutide with respect to its impact on liver and cardiometabolic health, the study authors said the agent offers significant potential in this patient population.
“Improvements in LFC, body weight and multiple markers of liver and cardiometabolic health with survodutide treatment in participants with early-stage MASLD suggest that this therapeutic agent has important benefits for reducing liver inflammation and cardiometabolic risk and underscore its potential for improving long-term outcomes in people with obesity and metabolic liver disease,” emphasized Kaplan and colleagues.
(Editor’s note: For related content, see “MRI-Derived Fat Quantification and Neurologic Impacts: What Emerging Research Reveals,” “MRI Study at ARRS Raises Questions About Disparities in Detection of MASLD” and “What a New MRI Meta-Analysis Reveals About AI-Powered Hippocampal Segmentation and Alzheimer’s Disease.”)
In regard to study limitations, the authors acknowledged the short duration of the study (48 weeks) and that the cohort was largely comprised of White patients.
