Decreases in circulating ANGPTL3 /8 concentrations following retatrutide treatment parallel reductions in serum lipids
Authors' conclusion
Together, these results suggest that the GCGR agonism of retatrutide could lead to reduced circulating ANGPTL3/8 concentrations, which may then contribute to decreases in TG and LDL-C levels.
Study context
- Population
- Participants with T2D, and participants with obesity or overweight without diabetes, in two phase 2 retatrutide trials; primary human hepatocytes
- Comparison
- Retatrutide doses vs baseline; in vitro retatrutide, GIP, GLP-1, glucagon and GCG and a GCG receptor (GCGR) antagonist antibody
- Primary endpoint
- Percent change from baseline in ANGPTL3/8, ANGPTL4/8, ANGPTL3 and ANGPTL4 concentrations
Methodological detailsin vitro primary human hepatocytes
- In vitro primary human hepatocytes
Primary result
As reported in the abstract
ANGPTL3/8 concentrations
- ANGPTL3/8 reductions with retatrutide 8 and 12 mg in participants with T2D
- ANGPTL3/8 reductions with retatrutide 1, 4, 8 and 12 mg in participants with obesity or overweight without diabetes
- ANGPTL3/8 decreases paralleled retatrutide-induced reductions in triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C)
- Post-hoc analysis
Further findings
ANGPTL3/8 secretion in primary human hepatocytes (in vitro)
- Glucagon and retatrutide decreased ANGPTL3/8 secretion; reductions blocked by GCGR antagonist antibody
Original publication
Decreases in circulating ANGPTL3 /8 concentrations following retatrutide treatment parallel reductions in serum lipids. Diabetes Obes Metab. Published 29 July 2025. doi:10.
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