Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: a randomised, placebo-controlled, double-blind, parallel-group study

Christian Seerup Frandsen; Thomas Fremming Dejgaard; Henrik Ullits Andersen; Jens Juul Holst; Bolette Hartmann; Birger Thorsteinsson; Sten Madsbad

doi:10.1111/dom.12830

Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: a randomised, placebo-controlled, double-blind, parallel-group study

Christian Seerup Frandsen, Thomas Fremming Dejgaard, Henrik Ullits Andersen, Jens Juul Holst, Bolette Hartmann, Birger Thorsteinsson, Sten Madsbad

16 Citations (Scopus)

Abstract

Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs inhibit glucagon secretion and delay the gastric emptying (GE) rate and may impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA liraglutide on counterregulatory responses and GE rate during hypoglycaemia in persons with T1D. Materials and methods: In a 12-week, randomized, double-blind, placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c ≥8% (64 mmol/mol) were randomly assigned (1:1) to liraglutide 1.2 mg once daily or placebo as add-on to insulin treatment. Before and at end of treatment a hypoglycaemic clamp (plasma glucose target 2.5 mmol/L) was carried out, followed by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under the paracetamol curve and time to peak). Secondary endpoints included changes in glycaemic recovery, counter-regulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure and heart rate. Results: During the period June 2013 to October 2014, 20 patients were enrolled. After 12 weeks of treatment, changes in GE rates did not differ significantly between groups (P =.96), with no significant changes from baseline, whether evaluated from AUCs or time to peak. The secondary endpoints, glycaemic recovery, counter-regulatory hormone responses, systolic blood pressure and GLP-1 and PP responses, were also similar. Heart rate increased with liraglutide from 69 ± 4 to 80 ± 5 beats/min (P =.02). Conclusions: Liraglutide does not compromise glycaemic recovery, GE rate or counter-regulatory hormone responses in T1D patients during hypoglycaemia. No treatment-related safety issues were identified.

Original language	English
Journal	Diabetes, Obesity and Metabolism
Volume	19
Issue number	6
Pages (from-to)	773-782
Number of pages	10
ISSN	1462-8902
DOIs	https://doi.org/10.1111/dom.12830
Publication status	Published - Jun 2017

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Frandsen, C. S., Dejgaard, T. F., Andersen, H. U., Holst, J. J., Hartmann, B., Thorsteinsson, B., & Madsbad, S. (2017). Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: a randomised, placebo-controlled, double-blind, parallel-group study. Diabetes, Obesity and Metabolism, 19(6), 773-782. https://doi.org/10.1111/dom.12830

Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia : a randomised, placebo-controlled, double-blind, parallel-group study. / Frandsen, Christian Seerup; Dejgaard, Thomas Fremming; Andersen, Henrik Ullits et al.

In: Diabetes, Obesity and Metabolism, Vol. 19, No. 6, 06.2017, p. 773-782.

Research output: Contribution to journal › Journal article › Research › peer-review

Frandsen, CS, Dejgaard, TF, Andersen, HU, Holst, JJ , Hartmann, B, Thorsteinsson, B & Madsbad, S 2017, 'Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: a randomised, placebo-controlled, double-blind, parallel-group study', Diabetes, Obesity and Metabolism, vol. 19, no. 6, pp. 773-782. https://doi.org/10.1111/dom.12830

Frandsen CS, Dejgaard TF, Andersen HU, Holst JJ , Hartmann B, Thorsteinsson B et al. Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: a randomised, placebo-controlled, double-blind, parallel-group study. Diabetes, Obesity and Metabolism. 2017 Jun;19(6):773-782. doi: 10.1111/dom.12830

Frandsen, Christian Seerup ; Dejgaard, Thomas Fremming ; Andersen, Henrik Ullits et al. / Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia : a randomised, placebo-controlled, double-blind, parallel-group study. In: Diabetes, Obesity and Metabolism. 2017 ; Vol. 19, No. 6. pp. 773-782.

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title = "Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: a randomised, placebo-controlled, double-blind, parallel-group study",

abstract = "Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs inhibit glucagon secretion and delay the gastric emptying (GE) rate and may impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA liraglutide on counterregulatory responses and GE rate during hypoglycaemia in persons with T1D. Materials and methods: In a 12-week, randomized, double-blind, placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c ≥8% (64 mmol/mol) were randomly assigned (1:1) to liraglutide 1.2 mg once daily or placebo as add-on to insulin treatment. Before and at end of treatment a hypoglycaemic clamp (plasma glucose target 2.5 mmol/L) was carried out, followed by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under the paracetamol curve and time to peak). Secondary endpoints included changes in glycaemic recovery, counter-regulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure and heart rate. Results: During the period June 2013 to October 2014, 20 patients were enrolled. After 12 weeks of treatment, changes in GE rates did not differ significantly between groups (P =.96), with no significant changes from baseline, whether evaluated from AUCs or time to peak. The secondary endpoints, glycaemic recovery, counter-regulatory hormone responses, systolic blood pressure and GLP-1 and PP responses, were also similar. Heart rate increased with liraglutide from 69 ± 4 to 80 ± 5 beats/min (P =.02). Conclusions: Liraglutide does not compromise glycaemic recovery, GE rate or counter-regulatory hormone responses in T1D patients during hypoglycaemia. No treatment-related safety issues were identified.",

author = "Frandsen, {Christian Seerup} and Dejgaard, {Thomas Fremming} and Andersen, {Henrik Ullits} and Holst, {Jens Juul} and Bolette Hartmann and Birger Thorsteinsson and Sten Madsbad",

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doi = "10.1111/dom.12830",

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TY - JOUR

T1 - Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia

T2 - a randomised, placebo-controlled, double-blind, parallel-group study

AU - Frandsen, Christian Seerup

AU - Dejgaard, Thomas Fremming

AU - Andersen, Henrik Ullits

AU - Holst, Jens Juul

AU - Hartmann, Bolette

AU - Thorsteinsson, Birger

AU - Madsbad, Sten

PY - 2017/6

Y1 - 2017/6

N2 - Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs inhibit glucagon secretion and delay the gastric emptying (GE) rate and may impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA liraglutide on counterregulatory responses and GE rate during hypoglycaemia in persons with T1D. Materials and methods: In a 12-week, randomized, double-blind, placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c ≥8% (64 mmol/mol) were randomly assigned (1:1) to liraglutide 1.2 mg once daily or placebo as add-on to insulin treatment. Before and at end of treatment a hypoglycaemic clamp (plasma glucose target 2.5 mmol/L) was carried out, followed by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under the paracetamol curve and time to peak). Secondary endpoints included changes in glycaemic recovery, counter-regulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure and heart rate. Results: During the period June 2013 to October 2014, 20 patients were enrolled. After 12 weeks of treatment, changes in GE rates did not differ significantly between groups (P =.96), with no significant changes from baseline, whether evaluated from AUCs or time to peak. The secondary endpoints, glycaemic recovery, counter-regulatory hormone responses, systolic blood pressure and GLP-1 and PP responses, were also similar. Heart rate increased with liraglutide from 69 ± 4 to 80 ± 5 beats/min (P =.02). Conclusions: Liraglutide does not compromise glycaemic recovery, GE rate or counter-regulatory hormone responses in T1D patients during hypoglycaemia. No treatment-related safety issues were identified.

AB - Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs inhibit glucagon secretion and delay the gastric emptying (GE) rate and may impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA liraglutide on counterregulatory responses and GE rate during hypoglycaemia in persons with T1D. Materials and methods: In a 12-week, randomized, double-blind, placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c ≥8% (64 mmol/mol) were randomly assigned (1:1) to liraglutide 1.2 mg once daily or placebo as add-on to insulin treatment. Before and at end of treatment a hypoglycaemic clamp (plasma glucose target 2.5 mmol/L) was carried out, followed by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under the paracetamol curve and time to peak). Secondary endpoints included changes in glycaemic recovery, counter-regulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure and heart rate. Results: During the period June 2013 to October 2014, 20 patients were enrolled. After 12 weeks of treatment, changes in GE rates did not differ significantly between groups (P =.96), with no significant changes from baseline, whether evaluated from AUCs or time to peak. The secondary endpoints, glycaemic recovery, counter-regulatory hormone responses, systolic blood pressure and GLP-1 and PP responses, were also similar. Heart rate increased with liraglutide from 69 ± 4 to 80 ± 5 beats/min (P =.02). Conclusions: Liraglutide does not compromise glycaemic recovery, GE rate or counter-regulatory hormone responses in T1D patients during hypoglycaemia. No treatment-related safety issues were identified.

U2 - 10.1111/dom.12830

DO - 10.1111/dom.12830

M3 - Journal article

C2 - 27868372

SN - 1462-8902

VL - 19

SP - 773

EP - 782

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 6

ER -