GLP-1 receptor agonists in type 1 diabetes: a proof-of-concept approach

To test potential efficacy of liraglutide, a GLP-1 receptor agonist, in subjects with type 1 diabetes (T1DM). We have recruited nine T1DM patients (age 40.1 +/- A 6.4 years, duration of diabetes 19.2 +/- A 8.8 years, BMI 24.3 +/- A 3.5 kg/m(2), HbA1c 8.2 +/- A 1.0 %-66 +/- A 11 mmol/mol, daily insulin dose: 0.6 +/- A 0.1 IU/kg) on continuous subcutaneous insulin therapy with undetectable C-peptide. In addition to existing treatment was administered in single-blind (a) therapy subcutaneously with 0.1 ml of saline solution for 3 days and (b) 0.1 ml of liraglutide (0.6 mg/day) for a further 3 days with daily glucose excursions recorded by continuous glucose monitoring. Adding liraglutide resulted in a significant reduction in mean blood glucose (138 +/- A 29 vs. 163 +/- A 29 mg/dl, p < 0.0001) and standard deviation (42 +/- A 9 vs. 60 +/- A 15 mg/dl, p < 0.0001). The area under the curve (AUC) for blood glucose > 140 mg/dl was also significantly reduced (22.2 +/- A 16.4 vs. 41.1 +/- A 19.7 mg/dl h, p < 0.05) with no difference in AUC for blood glucose < 70 mg/dl (liraglutide 0.7 +/- A 0.9 mg/dl h; placebo: 0.8 +/- A 1.4 mg/dl h, p = NS). Finally, adding liraglutide reduced daily insulin requirement (37.5 +/- A 17.2 vs. 42.9 +/- A 22.4 UI/day, p < 0.01). Short-term treatment with liraglutide, in T1DM, reduces average blood glucose, blood glucose variability and daily insulin requirement without increasing risk of hypoglycemia.