Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study

Int J Mol Sci. 2021 Aug 31;22(17):9454. doi: 10.3390/ijms22179454.

Abstract

Type 2 diabetes (T2D) represents one of the major health issues of this century. Despite the availability of an increasing number of anti-hyperglycemic drugs, a significant proportion of patients are inadequately controlled, thus highlighting the need for novel biomarkers to guide treatment selection. MicroRNAs (miRNAs) are small non-coding RNAs, proposed as useful diagnostic/prognostic markers. The aim of our study was to identify a miRNA signature occurring in responders to glucagon-like peptide 1 receptor agonists (GLP1-RA) therapy. We investigated the expression profile of eight T2D-associated circulating miRNAs in 26 prospectively evaluated diabetic patients in whom GLP1-RA was added to metformin. As expected, GLP1-RA treatment induced significant reductions of HbA1c and body weight, both after 6 and 12 months of therapy. Of note, baseline expression levels of the selected miRNAs revealed two distinct patient clusters: "high expressing" and "low expressing". Interestingly, a significantly higher percentage of patients in the high expression group reached the glycemic target after 12 months of treatment. Our findings suggest that the evaluation of miRNA expression could be used to predict the likelihood of an early treatment response to GLP1-RA and to select patients in whom to start such treatment, paving the way to a personalized medicine approach.

Keywords: GLP1-RA; microRNAs; obesity; personalized medicine; type 2 diabetes.

MeSH terms

  • Adult
  • Biomarkers, Pharmacological / blood
  • Blood Glucose / analysis
  • Circulating MicroRNA / analysis*
  • Circulating MicroRNA / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • Middle Aged
  • Pilot Projects
  • Transcriptome / genetics

Substances

  • Biomarkers, Pharmacological
  • Blood Glucose
  • Circulating MicroRNA
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • MicroRNAs
  • Glucagon-Like Peptide 1
  • Glucose