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

N1 - This article is protected by copyright. All rights reserved.

PY - 2017/3/17

Y1 - 2017/3/17

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 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, randomised, double-blinded, 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, counterregulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure, and heart rate.RESULTS: During June 2013-October 2014, 20 patients were enrolled. After 12 weeks' treatment, changes in GE rates did not differ significantly between groups (p = 0.96), with no significant changes from baseline whether evaluated from AUCs or time to peak. The secondary endpoints: glycaemic recovery, counterregulatory 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 = 0.02).CONCLUSIONS: Liraglutide does not compromise glycaemic recovery, GE rate or counterregulatory hormone responses in T1D 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 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, randomised, double-blinded, 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, counterregulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure, and heart rate.RESULTS: During June 2013-October 2014, 20 patients were enrolled. After 12 weeks' treatment, changes in GE rates did not differ significantly between groups (p = 0.96), with no significant changes from baseline whether evaluated from AUCs or time to peak. The secondary endpoints: glycaemic recovery, counterregulatory 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 = 0.02).CONCLUSIONS: Liraglutide does not compromise glycaemic recovery, GE rate or counterregulatory hormone responses in T1D during hypoglycaemia. No treatment-related safety issues were identified.

U2 - 10.1111/dom.12830

DO - 10.1111/dom.12830

M3 - Journal article

C2 - 27868372

VL - 19

SP - 773

EP - 782

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 6

ER -