Insights from changes in NDEV biomarkers of metabolism: effects of PPARγ and GLP1 receptor agonists on brain metabolism
Authors' conclusion
Our findings demonstrate CNS-specific biomarker responses to both PPARγ agonists and GLP1 receptor agonists.
Study context
- Population
- Participants with unremitted depression after six months of treatment as usual (pioglitazone cohort); middle-aged participants at genetic risk for Alzheimer's disease (AD) (liraglutide cohort)two cohorts
- Comparison
- Pioglitazone vs placebo; liraglutide vs placebo
- Pioglitazonen = 12
- Liraglutiden = 15
- Primary endpoint
- Change in 11 Akt-mTOR pathway proteins in neuron-derived extracellular vesicles (NDEVs)
- Follow-up
- Before and after 12 weeks of treatment
Methodological detailsbiomarker analysis
- Biomarker analysis
Primary result
As reported in the abstract
NDEV Akt-mTOR pathway proteins · 12 weeks
| Outcome | Pioglitazone | Liraglutide |
|---|---|---|
| mTOR (Ser2448) response | 77% | 30% |
| Akt (Ser473) response | — not stated in the abstract | 40% |
— not stated in the abstract
- Pioglitazone vs Placebo: all P ≤ .02 — significant increases in GSK3β (Ser9), mTOR (Ser2448), RPS6 (Ser235/Ser236)
- Liraglutide vs Placebo: P = 0.04 — increased phosphorylated Akt (Ser473)
- Liraglutide vs Placebo: P = 0.025 — increased mTOR (Ser2448)
Further findings
Relation to peripheral insulin/glucose
- Effects appeared relatively independent from changes in fasting plasma insulin and 120-min OGTT glucose
Original publication
Insights from changes in NDEV biomarkers of metabolism: effects of PPARγ and GLP1 receptor agonists on brain metabolism. J Clin Endocrinol Metab. Published 17 April 2026. doi:10.
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