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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.

Kielgast U, Krarup T, Holst JJ, Madsbad S - Diabetes Care (2011)

Bottom Line: 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.Transient gastrointestinal adverse effects occurred in almost all patients treated with liraglutide.Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Hvidovre University Hospital, and Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark. urd.kielgast@hvh.regionh.dk

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.

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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.
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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.

Mentions: In both groups of liraglutide-treated patients, HbA1c decreased in week 4 (Table 1), but changes were not statistically different from the change in patients treated with insulin alone (−0.26 ± 0.1 and −0.47 ± 0.15 vs. −0.18 ± 0.1%; P = 0.7 and P = 0.12) in C-peptide–positive and –negative patients, respectively, whereas mean blood glucose (during continuous blood glucose monitoring) showed no change in either group (Table 1). In C-peptide–positive patients, time spent in hypoglycemia decreased significantly from 3.0 ± 0.9 to 1.0 ± 0.4 h (P = 0.03) (Fig. 1), but compared with patients treated with insulin alone, changes in hypoglycemia or hyperglycemia were not significant (−2.03 ± 0.70 vs. −0.49 ± 0.72 h, P = 0.17 and +0.38 ± 0.7 vs. −0.28 ± 0.5 h, P = 0.6). C-peptide–negative patients treated with liraglutide experienced no significant changes in time spent with hypo- or hyperglycemia, but normoglycemic time changed from 15.5 to 16.9 h (P = 0.4) as a result of a tendency (P = 0.17) for decreased hypoglycemia (Fig. 1). In patients treated with insulin alone, there were no changes in HbA1c (P = 0.1), mean blood glucose (P = 1.0), or 24-h glucose profiles (Fig. 1). In C-peptide–positive and in C-peptide–negative patients treated with liraglutide and insulin, fasting blood glucose (mmol/L) changed from 5.46 ± 0.46 to 5.95 ± 0.44 (P = 0.30), from 5.44 ± 0.64 to 6.50 ± 0.35 (P = 0.09), and from 5.67 ± 0.61 to 6.54 ± 1.09 (P = 0.35); peak postprandial blood glucose (mmol/L) from 8.09 ± 0.48 to 8.98 ± 0.54 (P = 0.08), from 11.12 ± 0.44 to 10.43 ± 0.86 (P = 0.43), and from 11.32 ± 1.12 to 10.43 (P = 0.54); and differences changed from 2.51 ± 0.62 to 2.76 ± 0.62 (P = 0.43), from 4.64 ± 1.03 to 2.77 ± 0.45 (P = 0.07), and from 4.73 ± 0.79 to 3.58 ± 0.90 (P = 0.31). Thus, the effect of liraglutide was not predominantly exerted via lowering of postprandial glucose excursions.


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.

Kielgast U, Krarup T, Holst JJ, Madsbad S - Diabetes Care (2011)

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.
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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.
Mentions: In both groups of liraglutide-treated patients, HbA1c decreased in week 4 (Table 1), but changes were not statistically different from the change in patients treated with insulin alone (−0.26 ± 0.1 and −0.47 ± 0.15 vs. −0.18 ± 0.1%; P = 0.7 and P = 0.12) in C-peptide–positive and –negative patients, respectively, whereas mean blood glucose (during continuous blood glucose monitoring) showed no change in either group (Table 1). In C-peptide–positive patients, time spent in hypoglycemia decreased significantly from 3.0 ± 0.9 to 1.0 ± 0.4 h (P = 0.03) (Fig. 1), but compared with patients treated with insulin alone, changes in hypoglycemia or hyperglycemia were not significant (−2.03 ± 0.70 vs. −0.49 ± 0.72 h, P = 0.17 and +0.38 ± 0.7 vs. −0.28 ± 0.5 h, P = 0.6). C-peptide–negative patients treated with liraglutide experienced no significant changes in time spent with hypo- or hyperglycemia, but normoglycemic time changed from 15.5 to 16.9 h (P = 0.4) as a result of a tendency (P = 0.17) for decreased hypoglycemia (Fig. 1). In patients treated with insulin alone, there were no changes in HbA1c (P = 0.1), mean blood glucose (P = 1.0), or 24-h glucose profiles (Fig. 1). In C-peptide–positive and in C-peptide–negative patients treated with liraglutide and insulin, fasting blood glucose (mmol/L) changed from 5.46 ± 0.46 to 5.95 ± 0.44 (P = 0.30), from 5.44 ± 0.64 to 6.50 ± 0.35 (P = 0.09), and from 5.67 ± 0.61 to 6.54 ± 1.09 (P = 0.35); peak postprandial blood glucose (mmol/L) from 8.09 ± 0.48 to 8.98 ± 0.54 (P = 0.08), from 11.12 ± 0.44 to 10.43 ± 0.86 (P = 0.43), and from 11.32 ± 1.12 to 10.43 (P = 0.54); and differences changed from 2.51 ± 0.62 to 2.76 ± 0.62 (P = 0.43), from 4.64 ± 1.03 to 2.77 ± 0.45 (P = 0.07), and from 4.73 ± 0.79 to 3.58 ± 0.90 (P = 0.31). Thus, the effect of liraglutide was not predominantly exerted via lowering of postprandial glucose excursions.

Bottom Line: 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.Transient gastrointestinal adverse effects occurred in almost all patients treated with liraglutide.Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Hvidovre University Hospital, and Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark. urd.kielgast@hvh.regionh.dk

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.

Show MeSH