Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids
- Design
- Randomized trial · Unknown outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidencePost-hoc biomarker analysis of two phase 2 human trials (people with type 2 diabetes, and people with obesity or overweight without diabetes) plus in-vitro human hepatocyte experiments; the outcomes are blood protein and lipid changes, not clinical outcomes.
- Could weight loss explain it?
- PossiblyHuman trial data: ANGPTL3/8 decreases paralleled reductions in triglycerides and LDL-C, and the abstract does not separate them from weight loss.
- Study tier
- Study tier 3Post-hoc biomarker analysis of two phase 2 human RCTs plus in-vitro hepatocyte work; exploratory, with no clinical outcomes, so low.
- Assessment
- Version 4 · Checked against the source by AI · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; quoted from abstract conclusions] 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.
01Findings
What the study reported
- Drugs
- Retatrutide
- Dose
- 1, 4, 8 and 12 mg
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- mixed (one trial in type 2 diabetes, one without diabetes)
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- not extracted
- Randomization
- no
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- VERY_INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Peer review status
- yes
Methodological notes
Post-hoc biomarker analysis of two randomized phase 2 retatrutide trials, plus in-vitro human hepatocyte experiments; not a randomized test of these outcomes.
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- Eli Lilly, Lilly
- Sponsor role
- not reported in abstract
- Author conflicts
- All authors are employees and shareholders of Eli Lilly and Company.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Eli Lilly
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[AIMS] The aim of this study was to determine if retatrutide, a triple agonist of glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon-like peptide 1 (GLP-1) receptor and glucagon (GCG) receptor, may lower serum triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels in part by decreasing circulating concentrations of the angiopoietin-like protein 3/8 complex (ANGPTL3/8). [MATERIALS AND METHODS] In post-hoc analyses of two phase 2 retatrutide trials, concentrations of ANGPTL3/8, ANGPTL4/8 complex (ANGPTL4/8), ANGPTL3 and ANGPTL4 were measured using dedicated immunoassays to determine percent changes from baseline. Correlations of ANGPTL protein and complex levels with lipid and metabolic parameters at baseline were analysed. Correlations of the changes in ANGPTL protein and complex levels versus the changes in lipid and metabolic parameters at study endpoints were also analysed. Direct effects of retatrutide itself, GIP, GLP-1, GCG and a GCG receptor (GCGR) antagonist antibody on ANGPTL3/8 secretion were studied in vitro using primary human hepatocytes. [RESULTS] ANGPTL3/8 reductions were observed with 8 and 12 mg retatrutide doses in participants with type 2 diabetes, and with 1, 4, 8 and 12 mg retatrutide doses in participants with obesity or overweight but without diabetes. In both cases, ANGPTL3/8 decreases paralleled retatrutide-induced reductions in TG and LDL-C. In primary human hepatocytes, both glucagon and retatrutide decreased ANGPTL3/8 secretion, and these reductions were blocked with the GCGR antagonist antibody. [CONCLUSIONS] 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.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 30, 2026 | 40726454 first ingestion |