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Usefulness of circulating EPAC1 as biomarkers of therapeutic response to GLP-1 receptor agonists

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Abstract

Aims

The response to Glucagon-like peptide-1 receptor agonists (GLP-1RAs) is highly varia-ble among patients. Thus, the identification of predictive biomarkers of therapeutic response to GLP-1 RA could help us to optimize the use of this class of drugs. GLP-1RAs increase exchange proteins directly activated by cAMP (EPAC). The aim of the present study was to assess whether the increase of EPAC1 after GLP-1RAs treatment could be a biomarker of clinical response.

Methods

After showing that GLP-1 (10 ng/mL) significantly increased the expression of EPAC1 in human endo-thelial vascular cells (HUVEC), a pilot clinical study was planned. For this purpose 49 patients with type 2 diabetes who started treatment with liraglutide were included. EPAC1 concentration was determined by ELISA before and at one month of liraglutide treatment.

Results

We found that serum concentration of EPAC1 increased significantly after treatment with liraglutide. Only in those patients in whom EPAC1 increased (64%), a significant decrease in HbA1c, LDL-C, body mass index (BMI), and waist circumference was shown.

Conclusions

This pilot study suggests that the increase of circulating EPAC1 after GLP-1RAs treatment could be a useful biomarker to predict clinical GLP1-RAs response.

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Data availability

All data relevant to the study are included in the article. Other study information is available from the corresponding author.

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Funding

This research was funded by a grant from the Generalitat de Catalunya (2017SGR01144).

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Authors and Affiliations

Authors

Contributions

CH, FG and RS conceived the study concept and design, interpreted data, and contributed to critically revising the manuscript. OS, MG, CA, and SG contributed to the collection, analyses and interpretation of data. CH and FG drafted the manuscript. All authors approved the final article. RS and FG obtained funding. RS is the guarantor of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Rafael Simó.

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Conflict of interest

The authors have no competing interests to declare.

Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Vall d’Hebron University Hospital (PR(AG)32/2016). All the subjects provided written informed consent before study entry.

Informed consent

All the subjects provided written informed consent before the study entry.

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Hernández, C., Gómez-Peralta, F., Simó-Servat, O. et al. Usefulness of circulating EPAC1 as biomarkers of therapeutic response to GLP-1 receptor agonists. Acta Diabetol 59, 1437–1442 (2022). https://doi.org/10.1007/s00592-022-01928-6

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  • DOI: https://doi.org/10.1007/s00592-022-01928-6

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