Dataset Information

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.

SUBMITTER: Formichi C

PROVIDER: S-EPMC8431190 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Formichi Caterina C Fignani Daniela D Nigi Laura L Grieco Giuseppina Emanuela GE Brusco Noemi N Licata Giada G Sabato Claudia C Ferretti Elisabetta E Sebastiani Guido G Dotta Francesco F

International journal of molecular sciences 20210831 17

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 pepti ...[more]

PMID: 34502360

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Project description:BackgroundUse of SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1-RA) among older adults with type 2 diabetes (T2D) has been limited.ObjectiveTo examine factors associated with initiation of an SGLT2i or GLP-1RA among Medicare beneficiaries with T2D in the early years after their market approval, with a particular focus on formulary restrictions (e.g. prior authorization, step therapy requirements, higher co-pays).MethodsA retrospective cohort study using data from a 5% random sample of Medicare beneficiaries with T2D followed from 1/1/2015-12/31/16. Formulary restrictiveness was defined as: (1) the number of target drugs (i.e. SGLT2is or GLP1-RAs) included in tiers 1-3 of a beneficiary's formulary (greater number of drugs in tiers 1-3 being less restrictive) and (2) the number of drugs without prior authorization or step therapy (requirement to try less expensive drugs prior to "stepping up" to more expensive therapies). We used multivariable logistic regression models to estimate the association between measures of formulary restrictiveness and initiation of a target drug, controlling for patient demographics, diabetes duration, clinical comorbidities, and provider specialty.ResultsAmong 112,985 beneficiaries with T2D, 5,619 (5%) initiated an SGLT2i or GLP1-RA. After adjusting for baseline characteristics, patients enrolled in formularies with ≥ 2 target drugs available in tiers 1-3 had 17% higher odds of initiating an SGLT2i or GLP1-RA (aOR 1.17, 95% CI 1.05-1.31) compared to patients enrolled in formularies with 0 drugs available in tiers 1-3. There was no significant association between the number of drugs without prior authorization or step therapy requirements and initiation of a target drug (aOR 0.96, 95% CI, 0.85-1.09). Age 75 years or older (vs < 65, aOR 0.23, 95% CI 0.21-0.26) and black race (vs white, aOR 0.65, 95% CI 0.59-0.71) were associated with lower odds of initiating a target drug.ConclusionsHaving a greater number of target drugs available on less expensive formulary tiers is associated with increased odds of initiating an SGLT2i or GLP-1RA among Medicare beneficiaries with T2D.

Project description:IntroductionDiabetic Kidney Disease (DKD) is the main cause of end-stage renal disease in the developed world. The current treatment of the DKD with renin-angiotensin system (RAS) blockade does not totally halt the progression to end stage kidney disease. Currently, several drugs have shown to delay DKD progression such as sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like-1 receptor agonists (GLP-1RA). We hypothesized that by combining several drugs that prevent DKD progression on top of RAS blockade a synergistic effect would be achieved in terms of cardiorenal protection. In the present study, we analysed if the combination of a RAS blocker (ramipril) with a SGLT2i (empagliflozin) and/or GLP-1RA (semaglutide) in a type 2 diabetic mouse model could have add-on effects in kidney and heart protection.MethodsMale and female uninephrectomized type 2 diabetic db/db mice were treated with empagliflozin and/or semaglutide on top of ramipril during 8 weeks. During the study body weight, water and food intake were weekly monitored, glycaemia biweekly and albuminuria and glomerular filtration rate (GFR) before and after the treatment. At the end of the experiment, kidney and heart were isolated for histological and gene expression studies as well as for intrarenal RAS state assessment.ResultsSemaglutide combined with ramipril and/or empagliflozin significantly decreased albuminuria but only when combined with both compounds, semaglutide further decreased blood glucose, glomerular hyperfiltration in male mice and glomerular mesangial matrix expansion. In kidney, only the triple treatment with empagliflozin, semaglutide and ramipril reduced the expression of the proinflammatory and profibrotic genes ccl2 and TGFß1. In addition, the combination of empagliflozin and semaglutide on top of RAS blockade was superior in decreasing cardiomyocyte hypertrophy and heart fibrosis in db/db mice.DiscussionOur results suggest that the combination of SGLT2i with GLP-1RA is superior in cardiorenal protection in DKD than the drugs administered alone on top of RAS blockade.

Dataset Information

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

Publications

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

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