Retatrutide And Lipid And Metabolite Profiles In Participants With Obesity With Or Without Type 2 Diabetes
- Design
- Randomized trial · 495 participants · Unknown outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationParticipants had obesity, either without type 2 diabetes (obesity trial, n=282) or with it (T2D trial, n=213); age and BMI not reported in abstract; effects may be mediated by weight loss.
- Could weight loss explain it?
- PossiblyMediation analysis estimated that metabolite changes accounted for 23.2% of the weight-loss response without T2D and 12.7% with T2D; it did not test effects independent of weight loss.
- Study tier
- Study tier 2[Auto] Randomized trial of moderate size; outcome type and follow-up limit certainty (auto-provisional).
- 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.
In a post-hoc exploratory analysis of two phase 2 trials, retatrutide changed blood markers linked to fat burning and insulin resistance; these are biomarkers only, and no cardiovascular outcomes were measured.
01Findings
What the study reported
- Drugs
- Dulaglutide, Retatrutide
- Dose
- 1, 4, 8 or 12 mg (obesity trial); 0.5, 4, 8 or 12 mg (T2D trial)
- Comparator
- placebo; dulaglutide 1.5 mg in the T2D trial
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- 48 weeks (obesity trial, without T2D); 36 weeks (T2D trial)
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- mixed (one trial without and one with type 2 diabetes)
- Sample size
- 495
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 495
- Randomization
- yes
- Blinding
- not stated
- Comparator
- placebo; dulaglutide 1.5 mg in the T2D trial
- Follow up duration
- 48 weeks (obesity trial, without T2D); 36 weeks (T2D trial)
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
Methodological notes
Post-hoc exploratory analysis of stored fasting samples from two randomized, placebo-controlled phase 2 trials; not a randomized test of these outcomes.
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- not available in metadata
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[CONTEXT] In phase 2 trials, retatrutide reduced body weight, hemoglobin A1c, and improved the lipid profiles of participants living with obesity, with and without T2D. [OBJECTIVE] Assess plasma metabolome and lipidome changes associated with retatrutide treatment. [DESIGN] Metabolomics and lipidomics were performed in fasting samples from two randomized, placebo-controlled phase 2 trials. Participants living with obesity with and without T2D were treated for 36 and 48 weeks, respectively. [SETTING] Post-hoc exploratory analysis. [PARTICIPANTS] 282 and 213 participants in the obesity and T2D trials, respectively. [INTERVENTION(S)] Obesity trial; retatrutide (1, 4, 8, 12 mg) or placebo. T2D trial: retatrutide (0.5, 4, 8, 12 mg) or placebo or dulaglutide (1.5 mg). [MAIN OUTCOME MEASURE(S)] Changes in metabolite and lipid levels with retatrutide treatment against baseline levels and placebo using multiplicity correction. [RESULTS] At both primary and study endpoints for both populations, higher doses of retatrutide were associated with changes in a cluster of metabolites comprising 3-hydroxybutyrate, acetylcarnitine, free carnitine and fatty acid-derived long-chain acylcarnitines. Mediation analyses suggested that changes in these biomarkers mediated 23.2% of the weight-reduction response in participants without T2D and that this mediation was blunted to 12.7% in participants with T2D. Retatrutide treatment was also associated with changes in metabolites associated with insulin resistance, including branched-chain amino acids and their catabolic products, 2-aminoadipic acid, 2-hydroxybutyrate, urate, and triglycerides enriched in short-chain and saturated acyl side chains. These changes were found in both study populations and sustained across study endpoints. [CONCLUSIONS] Retatrutide was associated with changes in two metabolic clusters related to fatty acid oxidation and insulin resistance in a direction associated with improved metabolic health and reduced cardiovascular risk.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 30, 2026 | 42135195 first ingestion |