Daily Dose: Novel “Triagonist” Resolves Steatosis in Patients with MASLD and Obesity

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

Last week, we reported on findings from a study abstract presented at the American Association for the Study of Liver Diseases’ annual scientific conference, The Liver Meeting 2023.

The study

Researchers conducted a substudy of a phase 2 clinical trial to investigate the effects of the novel triple hormone receptor agonist retatrutide on liver fat (LF) and its correlations with metabolic measures in persons with metabolic dysfunction-associated steatotic liver disease (MASLD).

In the phase 2 trial, a total of 338 adults aged 18-75 years with a body mass index (BMI) of ≥27 kg/m2 or ≥30 kg/m2 and ≥ 1 weight related condition (type 2 diabetes excluded) were randomly assigned in a 2:1:1:1:1:2:2 ratio to receive subcutaneous retatrutide 1 mg, 4 mg, 8 mg, or 12 mg or placebo once weekly for 48 weeks. Participants with ≥10% LF were included in the MASLD substudy.

The primary outcome was relative LF change from baseline (CFB) at 24 weeks.

Of the 338 participants enrolled in the original phase 2 trial, 98 (46.9% women) participated in the current substudy.

Findings

Results showed that mean LF at baseline ranged from 15.6% to 21.0% across treatment groups.

At 24 weeks, the mean relative LF CFB was 42.9% among participants who received retatrutide 1 mg, 57.0% among those in the 4 mg group, 81.4% in the 8 mg group, -82.4% in the 12 mg group, and +0.3% in the placebo group. The mean relative LF CFB at 48 weeks was 51.3% (1 mg), 59.0% (4 mg), 81.7% (8 mg), 86.0% (12 mg), and 4.6% (placebo) (all P<.001 vs placebo).

Authors' comment

“In subjects with MASLD, RETA 8 and 12 mg resolved steatosis in >85% of subjects. Near-maximal LF reductions were achieved at ~20% reductions in BW. LF reductions were linearly related with metabolic measures associated with improved insulin sensitivity and lipid metabolism."

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