TY - JOUR

T1 - Liraglutide-Induced Weight Loss May be Affected by Autonomic Regulation in Type 1 Diabetes

AU - Hansen, Christian Stevns

AU - Frandsen, Christian Seerup

AU - Fleischer, Jesper

AU - Vistisen, Dorte

AU - Holst, Jens Juul

AU - Tarnow, Lise

AU - Knop, Filip Krag

AU - Madsbad, Sten

AU - Andersen, Henrik Ullits

AU - Dejgaard, Thomas Fremming

PY - 2019

Y1 - 2019

N2 - The role of the autonomic nervous system in the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 1 diabetes is unknown. We assessed the association between autonomic function and weight loss induced by the GLP-1 RA liraglutide. Methods: Lira-1 was a randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of 1.8 mg liraglutide once-daily for 24 weeks in overweight patients with type 1 diabetes. Autonomic function was assessed by heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio), to the Valsalva maneuver and resting heart rate variability (HRV) indices. Associations between baseline the cardiovascular autonomic neuropathy (CAN) diagnosis (> 1 pathological non-resting test) and levels of test outcomes on liraglutide-induced weight loss was assessed by linear regression models. Results: Ninety-nine patients with mean age 48 (SD 12) years, HbA(1c) 70 (IQR 66;75) mmol/mol and BMI of 30 (SD 3) kg/m(2) were assigned to liraglutide (N = 50) or placebo (N = 49). The CAN diagnosis was not associated with weight loss. A 50% higher baseline level of the 30/15 ratio was associated with a larger weight reduction by liraglutide of -2.65 kg during the trial (95% CI: -4.60; -0.69; P = 0.009). Similar significant associations were found for several HRV indices. Conclusions: The overall CAN diagnosis was not associated with liraglutide-induced weight loss in overweight patients with type 1 diabetes. Assessed separately, better outcomes for several CAN measures were associated with higher weight loss, indicating that autonomic involvement in liraglutide-induced weight loss may exist.

AB - The role of the autonomic nervous system in the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 1 diabetes is unknown. We assessed the association between autonomic function and weight loss induced by the GLP-1 RA liraglutide. Methods: Lira-1 was a randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of 1.8 mg liraglutide once-daily for 24 weeks in overweight patients with type 1 diabetes. Autonomic function was assessed by heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio), to the Valsalva maneuver and resting heart rate variability (HRV) indices. Associations between baseline the cardiovascular autonomic neuropathy (CAN) diagnosis (> 1 pathological non-resting test) and levels of test outcomes on liraglutide-induced weight loss was assessed by linear regression models. Results: Ninety-nine patients with mean age 48 (SD 12) years, HbA(1c) 70 (IQR 66;75) mmol/mol and BMI of 30 (SD 3) kg/m(2) were assigned to liraglutide (N = 50) or placebo (N = 49). The CAN diagnosis was not associated with weight loss. A 50% higher baseline level of the 30/15 ratio was associated with a larger weight reduction by liraglutide of -2.65 kg during the trial (95% CI: -4.60; -0.69; P = 0.009). Similar significant associations were found for several HRV indices. Conclusions: The overall CAN diagnosis was not associated with liraglutide-induced weight loss in overweight patients with type 1 diabetes. Assessed separately, better outcomes for several CAN measures were associated with higher weight loss, indicating that autonomic involvement in liraglutide-induced weight loss may exist.

KW - liraglutide

KW - autonomic neuropathy

KW - weight loss

KW - insulin requirements

KW - type 1 diabetes

U2 - 10.3389/fendo.2019.00242

DO - 10.3389/fendo.2019.00242

M3 - Journal article

C2 - 31031712

VL - 10

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

SN - 1664-2392

M1 - 242

ER -