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.
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.
What it found
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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.
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.
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Authors and funding
7 authors.
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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.
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Registered trials
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