Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility

Henriette H Nerild; Andreas Brønden; Ida M Gether; Pernille H Hellmann; Mille Baekdal; Matthew P Gillum; Jens S Svenningsen; Bolette Hartmann; Naveen Rathor; Hanna Angelene; Jens F Rehfeld; Jens J Holst; Tina Vilsbøll; David P Sonne; Filip K Knop

doi:10.1111/dom.15017

Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility

Henriette H Nerild, Andreas Brønden, Ida M Gether, Pernille H Hellmann, Mille Baekdal, Matthew P Gillum, Jens S Svenningsen, Bolette Hartmann, Naveen Rathor, Hanna Angelene, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, David P Sonne, Filip K Knop^*

^*Corresponding author for this work

Abstract

AIM: Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment.

MATERIALS AND METHODS: In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2.

RESULTS: Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)].

CONCLUSION: Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.

Original language	English
Journal	Diabetes, Obesity and Metabolism
Volume	25
Issue number	6
Pages (from-to)	1632-1637
Number of pages	6
ISSN	1462-8902
DOIs	https://doi.org/10.1111/dom.15017
Publication status	Published - Jun 2023

Keywords

Adult
Blood Glucose/metabolism
Body Mass Index
Diabetes Mellitus, Type 2/complications
Double-Blind Method
Female
Gallbladder/metabolism
Humans
Liraglutide/pharmacology
Male
Middle Aged
Obesity/complications
Postprandial Period

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10.1111/dom.15017

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Nerild, H. H., Brønden, A., Gether, I. M., Hellmann, P. H., Baekdal, M., Gillum, M. P., Svenningsen, J. S., Hartmann, B., Rathor, N., Angelene, H., Rehfeld, J. F., Holst, J. J., Vilsbøll, T., Sonne, D. P., & Knop, F. K. (2023). Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility. Diabetes, Obesity and Metabolism, 25(6), 1632-1637. https://doi.org/10.1111/dom.15017

Nerild, HH , Brønden, A , Gether, IM , Hellmann, PH , Baekdal, M, Gillum, MP, Svenningsen, JS, Hartmann, B, Rathor, N, Angelene, H, Rehfeld, JF, Holst, JJ, Vilsbøll, T , Sonne, DP & Knop, FK 2023, 'Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility', Diabetes, Obesity and Metabolism, vol. 25, no. 6, pp. 1632-1637. https://doi.org/10.1111/dom.15017

@article{16a036ae9ecb4b4d92b3eae4290296d8,

title = "Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility",

abstract = "AIM: Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment.MATERIALS AND METHODS: In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2.RESULTS: Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)].CONCLUSION: Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.",

keywords = "Adult, Blood Glucose/metabolism, Body Mass Index, Diabetes Mellitus, Type 2/complications, Double-Blind Method, Female, Gallbladder/metabolism, Humans, Liraglutide/pharmacology, Male, Middle Aged, Obesity/complications, Postprandial Period",

author = "Nerild, {Henriette H} and Andreas Br{\o}nden and Gether, {Ida M} and Hellmann, {Pernille H} and Mille Baekdal and Gillum, {Matthew P} and Svenningsen, {Jens S} and Bolette Hartmann and Naveen Rathor and Hanna Angelene and Rehfeld, {Jens F} and Holst, {Jens J} and Tina Vilsb{\o}ll and Sonne, {David P} and Knop, {Filip K}",

year = "2023",

month = jun,

doi = "10.1111/dom.15017",

language = "English",

volume = "25",

pages = "1632--1637",

journal = "Diabetes, Obesity and Metabolism",

issn = "1462-8902",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

TY - JOUR

T1 - Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility

AU - Nerild, Henriette H

AU - Brønden, Andreas

AU - Gether, Ida M

AU - Hellmann, Pernille H

AU - Baekdal, Mille

AU - Gillum, Matthew P

AU - Svenningsen, Jens S

AU - Hartmann, Bolette

AU - Rathor, Naveen

AU - Angelene, Hanna

AU - Rehfeld, Jens F

AU - Holst, Jens J

AU - Vilsbøll, Tina

AU - Sonne, David P

AU - Knop, Filip K

PY - 2023/6

Y1 - 2023/6

N2 - AIM: Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment.MATERIALS AND METHODS: In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2.RESULTS: Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)].CONCLUSION: Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.

AB - AIM: Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment.MATERIALS AND METHODS: In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2.RESULTS: Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)].CONCLUSION: Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.

KW - Adult

KW - Blood Glucose/metabolism

KW - Body Mass Index

KW - Diabetes Mellitus, Type 2/complications

KW - Double-Blind Method

KW - Female

KW - Gallbladder/metabolism

KW - Humans

KW - Liraglutide/pharmacology

KW - Male

KW - Middle Aged

KW - Obesity/complications

KW - Postprandial Period

UR - http://www.scopus.com/inward/record.url?scp=85150602958&partnerID=8YFLogxK

U2 - 10.1111/dom.15017

DO - 10.1111/dom.15017

M3 - Journal article

C2 - 36781820

VL - 25

SP - 1632

EP - 1637

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 6

ER -

Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility

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