Forskning
Udskriv Udskriv
Switch language
Bispebjerg Hospital - en del af Københavns Universitetshospital
Udgivet

Exendin(9-39)NH2 - recommendations for clinical use based on a systematic literature review

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Gasbjerg, Laerke Smidt ; Bari, Emilie Johanning ; Christensen, Mikkel Bring ; Knop, Filip Krag. / Exendin(9-39)NH2 - recommendations for clinical use based on a systematic literature review. I: Diabetes, Obesity and Metabolism. 2021 ; Bind 23, Nr. 11. s. 2419-2436.

Bibtex

@article{74569971816b4f5c978cb358a0f9dadf,
title = "Exendin(9-39)NH2 - recommendations for clinical use based on a systematic literature review",
abstract = "AIM: To present an overview of exendin(9-39)NH2 usage as a scientific tool in humans and provide recommendations for dosage and infusion regimes.METHODS: We systematically searched the literature on exendin(9-39)NH2 and included for review 44 clinical studies reporting use of exendin(9-39)NH2 in humans.RESULTS: Exendin(9-39)NH2 binds to the orthosteric binding site of the glucagon-like peptide-1 (GLP-1) receptor with high affinity. The plasma elimination half-life of exendin(9-39)NH2 after intravenous administration is ~30 minutes, requiring ~2.5 hours of constant infusion before steady-state plasma concentrations can be expected. Studies utilizing infusions with exendin(9-39)NH2 in humans have applied varying regimens (priming with a bolus or constant infusion) and dosages (continuous infusion rate range 30-900 pmol/kg/min) with subsequent differences in effects. Administration of exendin(9-39)NH2 in healthy individuals, patients with diabetes, obese patients, and patients who have undergone bariatric surgery significantly increases fasting and postprandial levels of glucose and glucagon, but has inconsistent effects on circulating concentrations of insulin and C-peptide, gastric emptying, appetite sensations, and food intake. Importantly, exendin(9-39)NH2 induces secretion of all L cell products (ie, in addition to GLP-1, also peptide YY, glucagon-like peptide-2, oxyntomodulin, and glicentin) complicating use of exendin(9-39)NH2 as a tool to study the isolated effect of GLP-1.CONCLUSIONS: Exendin(9-39)NH2 is selective for the GLP-1 receptor, with numerous and complex whole-body effects. To obtain GLP-1 receptor blockade in humans, we recommend an initial high-dose infusion, followed by a continuous infusion rate aiming at a ratio of exendin(9-39)NH2 to GLP-1 of 2000:1. Highlights Exendin(9-39)NH2 is a competitive antagonist of the human GLP-1 receptor. Exendin(9-39)NH2 has been used as a tool to delineate human GLP-1 physiology since 1998. Exendin(9-39)NH2 induces secretion of GLP-1 and other L cell products. Reported effects of exendin(9-39)NH2 on insulin levels and food intake are inconsistent. Here, we provide recommendations for the use of exendin(9-39)NH2 in clinical studies.",
keywords = "beta-cell function, dose-response relationship, drug mechanism, GLP-1, incretin physiology, pharmacokinetics",
author = "Gasbjerg, {Laerke Smidt} and Bari, {Emilie Johanning} and Christensen, {Mikkel Bring} and Knop, {Filip Krag}",
note = "This article is protected by copyright. All rights reserved.",
year = "2021",
month = nov,
doi = "10.1111/dom.14507",
language = "English",
volume = "23",
pages = "2419--2436",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "11",

}

RIS

TY - JOUR

T1 - Exendin(9-39)NH2 - recommendations for clinical use based on a systematic literature review

AU - Gasbjerg, Laerke Smidt

AU - Bari, Emilie Johanning

AU - Christensen, Mikkel Bring

AU - Knop, Filip Krag

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

PY - 2021/11

Y1 - 2021/11

N2 - AIM: To present an overview of exendin(9-39)NH2 usage as a scientific tool in humans and provide recommendations for dosage and infusion regimes.METHODS: We systematically searched the literature on exendin(9-39)NH2 and included for review 44 clinical studies reporting use of exendin(9-39)NH2 in humans.RESULTS: Exendin(9-39)NH2 binds to the orthosteric binding site of the glucagon-like peptide-1 (GLP-1) receptor with high affinity. The plasma elimination half-life of exendin(9-39)NH2 after intravenous administration is ~30 minutes, requiring ~2.5 hours of constant infusion before steady-state plasma concentrations can be expected. Studies utilizing infusions with exendin(9-39)NH2 in humans have applied varying regimens (priming with a bolus or constant infusion) and dosages (continuous infusion rate range 30-900 pmol/kg/min) with subsequent differences in effects. Administration of exendin(9-39)NH2 in healthy individuals, patients with diabetes, obese patients, and patients who have undergone bariatric surgery significantly increases fasting and postprandial levels of glucose and glucagon, but has inconsistent effects on circulating concentrations of insulin and C-peptide, gastric emptying, appetite sensations, and food intake. Importantly, exendin(9-39)NH2 induces secretion of all L cell products (ie, in addition to GLP-1, also peptide YY, glucagon-like peptide-2, oxyntomodulin, and glicentin) complicating use of exendin(9-39)NH2 as a tool to study the isolated effect of GLP-1.CONCLUSIONS: Exendin(9-39)NH2 is selective for the GLP-1 receptor, with numerous and complex whole-body effects. To obtain GLP-1 receptor blockade in humans, we recommend an initial high-dose infusion, followed by a continuous infusion rate aiming at a ratio of exendin(9-39)NH2 to GLP-1 of 2000:1. Highlights Exendin(9-39)NH2 is a competitive antagonist of the human GLP-1 receptor. Exendin(9-39)NH2 has been used as a tool to delineate human GLP-1 physiology since 1998. Exendin(9-39)NH2 induces secretion of GLP-1 and other L cell products. Reported effects of exendin(9-39)NH2 on insulin levels and food intake are inconsistent. Here, we provide recommendations for the use of exendin(9-39)NH2 in clinical studies.

AB - AIM: To present an overview of exendin(9-39)NH2 usage as a scientific tool in humans and provide recommendations for dosage and infusion regimes.METHODS: We systematically searched the literature on exendin(9-39)NH2 and included for review 44 clinical studies reporting use of exendin(9-39)NH2 in humans.RESULTS: Exendin(9-39)NH2 binds to the orthosteric binding site of the glucagon-like peptide-1 (GLP-1) receptor with high affinity. The plasma elimination half-life of exendin(9-39)NH2 after intravenous administration is ~30 minutes, requiring ~2.5 hours of constant infusion before steady-state plasma concentrations can be expected. Studies utilizing infusions with exendin(9-39)NH2 in humans have applied varying regimens (priming with a bolus or constant infusion) and dosages (continuous infusion rate range 30-900 pmol/kg/min) with subsequent differences in effects. Administration of exendin(9-39)NH2 in healthy individuals, patients with diabetes, obese patients, and patients who have undergone bariatric surgery significantly increases fasting and postprandial levels of glucose and glucagon, but has inconsistent effects on circulating concentrations of insulin and C-peptide, gastric emptying, appetite sensations, and food intake. Importantly, exendin(9-39)NH2 induces secretion of all L cell products (ie, in addition to GLP-1, also peptide YY, glucagon-like peptide-2, oxyntomodulin, and glicentin) complicating use of exendin(9-39)NH2 as a tool to study the isolated effect of GLP-1.CONCLUSIONS: Exendin(9-39)NH2 is selective for the GLP-1 receptor, with numerous and complex whole-body effects. To obtain GLP-1 receptor blockade in humans, we recommend an initial high-dose infusion, followed by a continuous infusion rate aiming at a ratio of exendin(9-39)NH2 to GLP-1 of 2000:1. Highlights Exendin(9-39)NH2 is a competitive antagonist of the human GLP-1 receptor. Exendin(9-39)NH2 has been used as a tool to delineate human GLP-1 physiology since 1998. Exendin(9-39)NH2 induces secretion of GLP-1 and other L cell products. Reported effects of exendin(9-39)NH2 on insulin levels and food intake are inconsistent. Here, we provide recommendations for the use of exendin(9-39)NH2 in clinical studies.

KW - beta-cell function

KW - dose-response relationship

KW - drug mechanism

KW - GLP-1

KW - incretin physiology

KW - pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=85113756793&partnerID=8YFLogxK

U2 - 10.1111/dom.14507

DO - 10.1111/dom.14507

M3 - Review

C2 - 34351033

VL - 23

SP - 2419

EP - 2436

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

IS - 11

ER -

ID: 67003341