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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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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.
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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.

Mentions: Fasting plasma glucose values were identical between study days (7.97 ± 0.8 mmol/L [week 0] and 8.01 ± 0.7 mmol/L [week 4]; P = 0.9) (Fig. 2A). Patients were injected with 7.44 and 5.44 units of fast-acting insulin in weeks 0 and 4, respectively (P = 0.04). Despite this, there were no differences of incremental or total area under the curve (AUC)0–120 min of plasma glucose between study days. Three patients stopped cycling prematurely because of hypoglycemia in both week 0 and 4 (one patient both times), and one additional patient had to stop prematurely after 25 min of cycling because of vomiting in week 4 (with plasma glucose 5.4 mmol/L). Thus, only six and five patients completed the cycling test in week 0 and 4, respectively. If hypoglycemia occurred (and exercise therefore terminated), the last observed plasma glucose value was carried forward. During cycling, total and incremental AUC120–190 min of plasma glucose changed from 487 ± 109 to 391 ± 55 mmol/L per min (P = 0.9) and from −150 ± 46 to −173 ± 30 mmol/L per min (P = 0.6) in week 0 and 4, respectively. The exercise-induced decline in plasma glucose (120–165 min) did not differ (0.102 ± 0.018 mmol/L per min [week 0] vs. 0.092 ± 0.0107 mmol/L per min [week 4]; P = 0.6). Fasting glucagon were identical (7.9 ± 0.3 vs. 7.1 ± 0.8 pmol/L) in week 0 and 4 (P = 0.4), but total AUC0–120 min of glucagon significantly decreased from 1,106 ± 92 pmol/L per min (week 0) to 845 ± 70 pmol/L per min (week 4) (P = 0.002); however, during exercise-induced decrease in plasma glucose, glucagon increased in both study days (Fig. 2B).


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)

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.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3120168&req=5

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.
Mentions: Fasting plasma glucose values were identical between study days (7.97 ± 0.8 mmol/L [week 0] and 8.01 ± 0.7 mmol/L [week 4]; P = 0.9) (Fig. 2A). Patients were injected with 7.44 and 5.44 units of fast-acting insulin in weeks 0 and 4, respectively (P = 0.04). Despite this, there were no differences of incremental or total area under the curve (AUC)0–120 min of plasma glucose between study days. Three patients stopped cycling prematurely because of hypoglycemia in both week 0 and 4 (one patient both times), and one additional patient had to stop prematurely after 25 min of cycling because of vomiting in week 4 (with plasma glucose 5.4 mmol/L). Thus, only six and five patients completed the cycling test in week 0 and 4, respectively. If hypoglycemia occurred (and exercise therefore terminated), the last observed plasma glucose value was carried forward. During cycling, total and incremental AUC120–190 min of plasma glucose changed from 487 ± 109 to 391 ± 55 mmol/L per min (P = 0.9) and from −150 ± 46 to −173 ± 30 mmol/L per min (P = 0.6) in week 0 and 4, respectively. The exercise-induced decline in plasma glucose (120–165 min) did not differ (0.102 ± 0.018 mmol/L per min [week 0] vs. 0.092 ± 0.0107 mmol/L per min [week 4]; P = 0.6). Fasting glucagon were identical (7.9 ± 0.3 vs. 7.1 ± 0.8 pmol/L) in week 0 and 4 (P = 0.4), but total AUC0–120 min of glucagon significantly decreased from 1,106 ± 92 pmol/L per min (week 0) to 845 ± 70 pmol/L per min (week 4) (P = 0.002); however, during exercise-induced decrease in plasma glucose, glucagon increased in both study days (Fig. 2B).

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