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

Apr 25, 2025Journal of translational medicine

Effects of single and combined GLP-1 treatments on small RNA patterns in type 2 diabetes

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Abstract

GLP-1 receptor agonists (GLP-1RAs) are associated with significant changes in specific non-exosomal in type 2 diabetes patients, influencing cardiovascular health and weight loss.

  • GLP-1RA combined with metformin modulated non-exosomal miR-27b, miR-130a, and miR-210a, which are linked to cardiovascular health.
  • In patients on metformin, higher baseline levels of miR-378-3p or miR-126-3p correlated with improved HbA1c after one year of GLP-1RA therapy.
  • Greater than 5% weight loss was associated with higher baseline levels of miR-15a-5p.
  • Preclinical studies indicated that GLP-1RA monotherapy increased cardiovascular action through non-exosomal miR-29b-3p, miR-34a-5p, miR-26a-5p, miR-181a-5p, and miR-93-5p.
  • GLP-1RA monotherapy reduced hepatic lipid accumulation in T2DM models with non-alcoholic fatty liver disease via modulation of ABHD6 mRNA by non-exosomal miR-5120.
  • No clinical studies reported on exosomal miRNAs, but a preclinical study linked GLP-1RA-induced exosomal let-7c-2-3p/miR-322-3p to bone protection.

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Key numbers

> 5%
Weight Loss Correlation
Weight loss in patients on GLP-1RA therapy
1 year
HbA1c Improvement Predictor
Timeframe for assessing treatment response in patients
11
Studies Included
Total studies reviewed for GLP-1RA effects on

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