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Diabetes Care. 2016 Feb;39(2):250-7. doi: 10.2337/dc15-0258. Epub 2015 Aug 4.

Markers of β-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes.

Author information

1
National Institute for Health Research Exeter Clinical Research Facility, University of Exeter Medical School and Royal Devon and Exeter National Health Service Foundation Trust, Exeter, U.K. angus.jones@exeter.ac.uk.
2
National Institute for Health Research Exeter Clinical Research Facility, University of Exeter Medical School and Royal Devon and Exeter National Health Service Foundation Trust, Exeter, U.K.
3
Institute of Health Research, University of Exeter Medical School, Exeter, U.K.

Abstract

OBJECTIVE:

To assess whether clinical characteristics and simple biomarkers of β-cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS:

We prospectively studied 620 participants with type 2 diabetes and HbA1c ≥58 mmol/mol (7.5%) commencing GLP-1RA therapy as part of their usual diabetes care and assessed response to therapy over 6 months. We assessed the association between baseline clinical measurements associated with β-cell failure and glycemic response (primary outcome HbA1c change 0-6 months) with change in weight (0-6 months) as a secondary outcome using linear regression and ANOVA with adjustment for baseline HbA1c and cotreatment change.

RESULTS:

Reduced glycemic response to GLP-1RAs was associated with longer duration of diabetes, insulin cotreatment, lower fasting C-peptide, lower postmeal urine C-peptide-to-creatinine ratio, and positive GAD or IA2 islet autoantibodies (P ≤ 0.01 for all). Participants with positive autoantibodies or severe insulin deficiency (fasting C-peptide ≤0.25 nmol/L) had markedly reduced glycemic response to GLP-1RA therapy (autoantibodies, mean HbA1c change -5.2 vs. -15.2 mmol/mol [-0.5 vs. -1.4%], P = 0.005; C-peptide <0.25 nmol/L, mean change -2.1 vs. -15.3 mmol/mol [-0.2 vs. -1.4%], P = 0.002). These markers were predominantly present in insulin-treated participants and were not associated with weight change.

CONCLUSIONS:

Clinical markers of low β-cell function are associated with reduced glycemic response to GLP-1RA therapy. C-peptide and islet autoantibodies represent potential biomarkers for the stratification of GLP-1RA therapy in insulin-treated diabetes.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01503112.

PMID:
26242184
PMCID:
PMC4894547
DOI:
10.2337/dc15-0258
[Indexed for MEDLINE]
Free PMC Article

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