Evidence boundary: Liver findings below come from a prespecified MRI substudy of Lilly’s investigated LY3437943. They are imaging results under that protocol, not claims about another material or a recommended use.
Investigators reported striking liver-fat changes in a randomized LY3437943 substudy—one of the most closely watched findings outside the primary body-weight and glycemic endpoints. The study offers a strong signal for imaging-defined steatosis and a clear rationale for dedicated liver research.
The MRI-PDFF substudy
A prespecified substudy enrolled 98 participants from the Phase 2 obesity trial who had sufficient liver fat at baseline. At week 24, relative liver-fat changes were approximately:
| Group | Relative liver-fat change |
|---|---|
| Lower dose | −42.9% |
| Intermediate dose | −57.0% |
| Higher dose | −81.4% |
| Highest dose | −82.4% |
| Placebo | +0.3% |
Imaging-defined liver-fat normalization below 5% occurred in 27%, 52%, 79%, and 86% of the retatrutide groups, compared with 0% for placebo.
These are large randomized imaging findings.
Why imaging is not the entire disease
MRI-PDFF quantifies hepatic fat. It does not directly show hepatocyte injury, inflammation, ballooning, fibrosis stage, cirrhosis progression, decompensation, transplantation, or mortality.
The substudy did not include liver biopsies. FIB-4 and enhanced liver fibrosis measures did not improve consistently, and the analyses were not multiplicity adjusted. Therefore, the evidence did not establish histologic steatohepatitis resolution or fibrosis regression.
What may explain the change?
Substantial weight loss commonly reduces liver fat. Retatrutide’s receptor profile could also contribute through metabolic mechanisms, but this substudy could not isolate a weight-independent effect or assign the result to the glucagon receptor.
Dedicated liver trials and biopsy or clinical-outcome evidence are needed to answer those questions.
Bottom line
The LY3437943 evidence includes strong preliminary MRI findings, with many participants reaching the study’s imaging-defined liver-fat threshold. This is a meaningful result within the substudy. Biopsy-based and longer-term research will determine whether the observed imaging changes extend to inflammation, fibrosis, and clinical liver outcomes.