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

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.

Circulating miRNA as potential biomarkers for diabetes mellitus type 2: should we focus on searching for sex differences?

“…It occurs that circulating miRNAs could also be used to predict the effects of DM2 therapy (Table 3). After 1 year of treatment with glucagon-like peptide 1 receptor agonists (GLP1-RA), patients with initially higher expression levels of eight circulating miRNAs had a better response to therapy than those with lower levels (Formichi et al 2021). In addition to the abovementioned examples, the recent results showed that circulating miRNA may be utilized to select a personalized diet model to prevent the development of DM2.…”

“…In the case of patients with cardiovascular diseases, initial high miR-150 along with low miR-29a, miR-28-3p, and miR-126 in subjects on a Mediterranean diet, and low initial level of miR-145 in subjects on low-fat high-complex carbohydrate diet, was associated with a higher risk of development DM2 (Jimenez-Lucena et al 2021). Therefore, the profile of circulating miRNAs may be also used to select a group of patients for a particular treatment in DM2 (Formichi et al 2021) and nutritional therapy to lower the risk of disease development (Jimenez-Lucena et al 2021).…”

Circulating microRNAs as clinically useful biomarkers for Type 2 Diabetes Mellitus: miRNomics from bench to bedside

“…This showed that the expression of miR-126-3p correlated positively with the reduction in fasting blood glucose (%) at T12. 52 Importantly, our work showed that miR-126-3p expression correlated positively with fasting glucose reduction (%) at T12. 52 Taken together, these studies consistently report the importance of circulating miR-126-3p in T2D.…”

“…52 Importantly, our work showed that miR-126-3p expression correlated positively with fasting glucose reduction (%) at T12. 52 Taken together, these studies consistently report the importance of circulating miR-126-3p in T2D. Overall, circulating miR-126-3p: (1) is significantly reduced in T2D patients and inversely associated with fasting glycamia; (2) is reduced in IGT patients and predicts the occurrence of T2D; (3) is a potential biomarker for both pharmacological (metformin/sitagliptin) and dietary therapies (low-fat vs Mediterranean diet); and (4) identifies the presence of cardiovascular disease in T2D patients.…”

“…Indeed, we have recently shown that miR-223-3p expression is higher in T2D patients who achieved the glycemic target (HbA1c < 7%) after 12 months of treatment with GLP1 analogues in combination with metformin, suggesting that low expression of this miRNA prior to GLP1 therapy may predict a worse glycemic outcome. 52 Overall, these studies show that miR-223-3p is a valid circulating biomarker for T2D. Indeed, miR-223-3p: (1) was reduced in plasma samples of T2D patients and in serum microvesicles; (2) it can distinguish prediabetic subjects into two categories, those that will likely develop diabetes from those that will not.…”