Evidence mapPaperPMID 40281607Full record

SynthesisJournal of translational medicine2025

Impact of monotherapy and combination therapy with glucagon-like peptide-1 receptor agonists on exosomal and non-exosomal MicroRNA signatures in type 2 diabetes mellitus: a systematic review.

Haifeng Yu, Maryam Davoudi, Sahar Sadegh-Nejadi, Xiaolei Miao, Molood Bagherieh, Reza Afrisham

Abstract readSystematic Review
In one paragraph

Synthesis in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
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

6 authors.

Haifeng YuHubei Key Laboratory of Diabetes and Angiopathy, School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, Hubei Province, China.
Maryam DavoudiDepartment of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Sahar Sadegh-NejadiDepartment of Clinical Laboratory, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Xiaolei MiaoHubei Key Laboratory of Diabetes and Angiopathy, School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, Hubei Province, China. 345701500@qq.com.
Molood BagheriehRamsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran. Baqeriyeh@gmail.com.
Reza AfrishamDepartment of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran. rafrisham@sina.tums.ac.ir.ORCID http://orcid.org/0000-0001-8064-118X

Funding

Department of Science and Technology, Hubei Provincial People's Government Q201810
6 · The paper itself

Abstract

backgroundGlucagon-like peptide-1 receptor agonist (GLP-1RAs) is a potent therapy for type 2 diabetes mellitus (T2DM) and obesity, especially in patients who are resistant to long-term insulin therapy. Although microRNAs have been linked to GLP-1 signaling, their role in GLP-1RA monotherapy and combination therapy remains unclear. This review synthesizes current evidence of GLP-1RA-induced exosomal and non-exosomal miRNA changes in human and animal models of T2DM.

methodsScopus, PubMed/Medline, Web of Science, and Google Scholar searches returned 83 studies, of which 11 met the study eligibility criteria (PROSPERO No: CRD42024586000).

resultsHuman studies showed GLP-1RA combined with metformin modulated non-exosomal miR-27b, miR-130a, and miR-210a, which were linked to cardiovascular health. In T2DM patients on metformin, higher baseline miR-378-3p or miR-126-3p correlated with greater HbA1c improvement after one year of GLP-1RA therapy. Notably, > 5% weight loss correlated with higher baseline levels of miR-15a-5p. Preclinical findings suggested GLP-1RA monotherapy increased cardiovascular action via non-exosomal miR-29b-3p, miR-34a-5p, miR-26a-5p, miR-181a-5p, and miR-93-5p. Silencing non-exosomal miR-204, miR-375, or miR-139-5p augmented exendin-4/liraglutide monotherapy-induced glucose-stimulated insulin secretion. Interestingly, GLP-1RA monotherapy reduced hepatic lipid accumulation in T2DM models with comorbid NAFLD via ABHD6 mRNA modulation by non-exosomal miR-5120. No clinical studies reported exosomal miRNAs, but a preclinical study linked GLP-1RA-induced exosomal let-7c-2-3p/miR-322-3p to bone protection in estrogen-deficient T2DM models.

conclusionGLP-1RAs, both as first-line and second-line therapies, are beneficial for T2DM complicated by obesity, NAFLD, cardio-metabolic disease, and postmenopausal osteoporosis. Longitudinal trials that incorporate innovative multi-omics approaches are essential for distinguishing their miRNA expression pattern from other anti-diabetics.

Indexed as

Diabetes Mellitus, Type 2ExosomesGlucagon-Like Peptide-1 Receptor AgonistsMicroRNAsAnimalsDrug Therapy, CombinationGlucagon-Like Peptide-1 ReceptorHumansMetforminGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsMetforminMicroRNAsDrug therapy, combinationExosomesGlucagon-like peptide-1 receptor agonistsMicroRNAsMonotherapyType 2 diabetes mellitus

Identifiers

PMID40281607
PMCPMC12032824

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.