Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function

Abstract

Objective: To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual β-cell function.

Research design and methods: Ten type 1 diabetic patients with residual β-cell function (C-peptide positive) and 19 without (C-peptide negative) were studied. All C-peptide-positive patients were treated with liraglutide plus insulin, whereas C-peptide-negative patients were randomly assigned to liraglutide plus insulin or insulin monotherapy. Continuous glucose monitoring with identical food intake and physical activity was performed before (week 0) and during (week 4) treatment. Differences in insulin dose; HbA1c; time spent with blood glucose<3.9, >10, and 3.9-9.9 mmol/L; and body weight were evaluated.

Results: Insulin dose decreased from 0.50±0.06 to 0.31±0.08 units/kg per day (P<0.001) in C-peptide-positive patients and from 0.72±0.08 to 0.59±0.06 units/kg per day (P<0.01) in C-peptide-negative patients treated with liraglutide but did not change with insulin monotherapy. HbA1c decreased in both liraglutide-treated groups. The percent reduction in daily insulin dose was positively correlated with β-cell function at baseline, and two patients discontinued insulin treatment. In C-peptide-positive patients, time spent with blood glucose<3.9 mmol/L decreased from 3.0 to 1.0 h (P=0.03). A total of 18 of 19 patients treated with liraglutide lost weight during treatment (mean [range] -2.3±0.3 kg [-0.5 to -5.1]; P<0.001). Transient gastrointestinal adverse effects occurred in almost all patients treated with liraglutide.

Conclusions: Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control.

Trial registration: ClinicalTrials.gov NCT00993720.

Figure 1

Blood glucose evaluated from 24 h continuous glucose monitoring as mean blood glucose during 3 days with self-reported identical meals and physical activity before (week 0) and during (week 4) treatment with liraglutide. A: A total of 10 type 1 diabetic patients with residual β-cell function treated with liraglutide and insulin. B: A total of nine type 1 diabetic patients without residual β-cell function treated with liraglutide and insulin. C: A total of 10 type 1 diabetic patients without residual β-cell function treated with insulin alone. *P < 0.05 between week 0 and week 4 within the same group.

Figure 2

Time course of plasma glucose (A) and glucagon (B) during a mixed meal followed by 45 min cycling (120–165 min) in nine type 1 diabetic patients before (week 0, blue circles) and during (week 4, red circles) treatment with liraglutide. Arrow: meal served. If two-way repeated-measures ANOVA resulted in significant difference (time × trial), Student paired t tests were performed at each time point. *P < 0.05.