Evidence mapPaperPMID 42434480Full record

ArticleMetabolism open2026

Direct effects of glucagon-like Peptide-1 receptor agonists on mitochondrial function in human-derived in vitro models: A systematic review and meta-analysis.

Zoe Lee Greenblatt, Atena Tork, Ivy Cruz, Erik D Fausak, Huy-An Tran, Mahima Krovidy, Cecilia Giulivi

Abstract read
In one paragraph

Article in Metabolism open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Zoe Lee GreenblattDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Atena TorkDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Ivy CruzDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Erik D FausakUniversity Library, University of California, Davis, CA, 95616, USA.
Huy-An TranDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Mahima KrovidyDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.
Cecilia GiuliviDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GLP-1 receptor agonists (e.g., semaglutide; GLP-1 RAs) treat Type 2 Diabetes and obesity, mainly by improving glycemic control, suppressing appetite, delaying gastric emptying, and inducing weight loss. Emerging evidence suggests they also directly affect mitochondrial function independently of systemic metabolism. To our knowledge, this is the first systematic review and meta-analysis examining direct mitochondrial effects of GLP-1 RAs in human-derived in vitro models. Of 1547 records identified (1203 screened after deduplication), 17 studies met the criteria, and only 11 contributed to the quantitative synthesis of mitochondrial outcomes. Outcomes included mitochondrial membrane potential (MMP), bioenergetics (ATP-linked oxygen consumption, respiration, ATP production), and mitochondrial reactive oxygen species (MitoROS). Meta-analysis demonstrated significantly improved bioenergetics (SMD = 1.109, 95% CI: 0.556-1.662, P < 0.001) and reduced MitoROS (SMD = -3.489, 95% CI: -6.690 to -0.288, P = 0.034) following GLP-1RA treatment. No significant effect on MMP was observed in the primary analysis (SMD = 0.997, 95% CI: -1.678 to 3.672, P = 0.459), although an exploratory sensitivity analysis excluding statistically identified outlying effect sizes suggested a potential improvement in MMP (SMD = 3.145, 95% CI: 2.147-4.144, P < 0.01); however, this finding should be interpreted cautiously. Overall certainty of the evidence was very low for the primary outcomes due to methodological limitations, substantial heterogeneity, imprecision, and publication bias in some outcomes. Only the MMP sensitivity analysis achieved low-certainty evidence. These findings suggest that GLP-1 RAs may directly promote mitochondrial health, but more rigorous, standardized, and independent studies are needed to confirm their relevance to whole-body physiology.

Indexed as

BioenergeticsGlucagon-like peptide-1 receptor agonistsMeta-analysisMitochondrial functionMitochondrial membrane potentialMitochondrial reactive oxygen speciesSystematic review

Identifiers

PMID42434480
PMCPMC13351396

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.