The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest

Sebastian Wiberg, Jesper Kjaergaard, Henrik Schmidt, Jakob Hartvig Thomsen, Martin Frydland, Matilde Winther-Jensen, Matias Greve Lindholm, Dan Eik Hofsten, Thomas Engstrom, Lars Køber, Jacob Eifer Moller, Christian Hassager

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm. INTERVENTIONS: Patients were randomized 1:1 to receive 6 hours and 15 minutes of infusion of either 17.4 μg of the glucagon-like peptide-1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained return of spontaneous circulation. The effects of exenatide were examined on the following prespecified covariates within the first 6 hours from study drug initiation: lactate level, blood glucose level, heart rate, mean arterial pressure, and combined dosage of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: The population consisted of 106 patients receiving either exenatide or placebo. During the first 6 hours from study drug initiation, the levels of blood glucose and lactate decreased 17% (95% CI, 8.9-25%; p = 0.0004) and 21% (95% CI, 6.0-33%; p = 0.02) faster in patients receiving exenatide versus placebo, respectively. Exenatide increased heart rate by approximately 10 beats per minute compared to placebo (p < 0.0001). There was no effect of exenatide on other hemodynamic variables. CONCLUSIONS: In comatose out-of-hospital cardiac arrest patients, infusion with exenatide lowered blood glucose and resulted in increased clearance of lactate as well as increased heart rate. The clinical importance of these physiologic effects remains to be investigated.

Original languageEnglish
JournalCritical Care Medicine
Volume46
Issue number2
Pages (from-to)E118-E125
ISSN0090-3493
DOIs
Publication statusPublished - Feb 2018

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Lactic Acid
Placebos
exenatide
Pharmaceutical Preparations
Arterial Pressure
Randomized Controlled Trials
Population

Keywords

  • exenatide
  • glucagon-like peptide-1 analogs
  • hemodynamics
  • lactate clearance
  • out-of-hospital cardiac arrest
  • Glucagon-Like Peptide 1/analogs & derivatives
  • Double-Blind Method
  • Humans
  • Middle Aged
  • Coma/blood
  • Male
  • Blood Glucose/drug effects
  • Out-of-Hospital Cardiac Arrest/complications
  • Heart Rate/drug effects
  • Female
  • Lactic Acid/metabolism
  • Hemodynamics/drug effects
  • Exenatide/pharmacology

Cite this

Wiberg, Sebastian ; Kjaergaard, Jesper ; Schmidt, Henrik ; Thomsen, Jakob Hartvig ; Frydland, Martin ; Winther-Jensen, Matilde ; Lindholm, Matias Greve ; Hofsten, Dan Eik ; Engstrom, Thomas ; Køber, Lars ; Moller, Jacob Eifer ; Hassager, Christian. / The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest. In: Critical Care Medicine. 2018 ; Vol. 46, No. 2. pp. E118-E125.
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abstract = "OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm. INTERVENTIONS: Patients were randomized 1:1 to receive 6 hours and 15 minutes of infusion of either 17.4 μg of the glucagon-like peptide-1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained return of spontaneous circulation. The effects of exenatide were examined on the following prespecified covariates within the first 6 hours from study drug initiation: lactate level, blood glucose level, heart rate, mean arterial pressure, and combined dosage of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: The population consisted of 106 patients receiving either exenatide or placebo. During the first 6 hours from study drug initiation, the levels of blood glucose and lactate decreased 17{\%} (95{\%} CI, 8.9-25{\%}; p = 0.0004) and 21{\%} (95{\%} CI, 6.0-33{\%}; p = 0.02) faster in patients receiving exenatide versus placebo, respectively. Exenatide increased heart rate by approximately 10 beats per minute compared to placebo (p < 0.0001). There was no effect of exenatide on other hemodynamic variables. CONCLUSIONS: In comatose out-of-hospital cardiac arrest patients, infusion with exenatide lowered blood glucose and resulted in increased clearance of lactate as well as increased heart rate. The clinical importance of these physiologic effects remains to be investigated.",
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author = "Sebastian Wiberg and Jesper Kjaergaard and Henrik Schmidt and Thomsen, {Jakob Hartvig} and Martin Frydland and Matilde Winther-Jensen and Lindholm, {Matias Greve} and Hofsten, {Dan Eik} and Thomas Engstrom and Lars K{\o}ber and Moller, {Jacob Eifer} and Christian Hassager",
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The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest. / Wiberg, Sebastian; Kjaergaard, Jesper; Schmidt, Henrik; Thomsen, Jakob Hartvig; Frydland, Martin; Winther-Jensen, Matilde; Lindholm, Matias Greve; Hofsten, Dan Eik; Engstrom, Thomas; Køber, Lars; Moller, Jacob Eifer; Hassager, Christian.

In: Critical Care Medicine, Vol. 46, No. 2, 02.2018, p. E118-E125.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest

AU - Wiberg, Sebastian

AU - Kjaergaard, Jesper

AU - Schmidt, Henrik

AU - Thomsen, Jakob Hartvig

AU - Frydland, Martin

AU - Winther-Jensen, Matilde

AU - Lindholm, Matias Greve

AU - Hofsten, Dan Eik

AU - Engstrom, Thomas

AU - Køber, Lars

AU - Moller, Jacob Eifer

AU - Hassager, Christian

PY - 2018/2

Y1 - 2018/2

N2 - OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm. INTERVENTIONS: Patients were randomized 1:1 to receive 6 hours and 15 minutes of infusion of either 17.4 μg of the glucagon-like peptide-1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained return of spontaneous circulation. The effects of exenatide were examined on the following prespecified covariates within the first 6 hours from study drug initiation: lactate level, blood glucose level, heart rate, mean arterial pressure, and combined dosage of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: The population consisted of 106 patients receiving either exenatide or placebo. During the first 6 hours from study drug initiation, the levels of blood glucose and lactate decreased 17% (95% CI, 8.9-25%; p = 0.0004) and 21% (95% CI, 6.0-33%; p = 0.02) faster in patients receiving exenatide versus placebo, respectively. Exenatide increased heart rate by approximately 10 beats per minute compared to placebo (p < 0.0001). There was no effect of exenatide on other hemodynamic variables. CONCLUSIONS: In comatose out-of-hospital cardiac arrest patients, infusion with exenatide lowered blood glucose and resulted in increased clearance of lactate as well as increased heart rate. The clinical importance of these physiologic effects remains to be investigated.

AB - OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm. INTERVENTIONS: Patients were randomized 1:1 to receive 6 hours and 15 minutes of infusion of either 17.4 μg of the glucagon-like peptide-1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained return of spontaneous circulation. The effects of exenatide were examined on the following prespecified covariates within the first 6 hours from study drug initiation: lactate level, blood glucose level, heart rate, mean arterial pressure, and combined dosage of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: The population consisted of 106 patients receiving either exenatide or placebo. During the first 6 hours from study drug initiation, the levels of blood glucose and lactate decreased 17% (95% CI, 8.9-25%; p = 0.0004) and 21% (95% CI, 6.0-33%; p = 0.02) faster in patients receiving exenatide versus placebo, respectively. Exenatide increased heart rate by approximately 10 beats per minute compared to placebo (p < 0.0001). There was no effect of exenatide on other hemodynamic variables. CONCLUSIONS: In comatose out-of-hospital cardiac arrest patients, infusion with exenatide lowered blood glucose and resulted in increased clearance of lactate as well as increased heart rate. The clinical importance of these physiologic effects remains to be investigated.

KW - exenatide

KW - glucagon-like peptide-1 analogs

KW - hemodynamics

KW - lactate clearance

KW - out-of-hospital cardiac arrest

KW - Glucagon-Like Peptide 1/analogs & derivatives

KW - Double-Blind Method

KW - Humans

KW - Middle Aged

KW - Coma/blood

KW - Male

KW - Blood Glucose/drug effects

KW - Out-of-Hospital Cardiac Arrest/complications

KW - Heart Rate/drug effects

KW - Female

KW - Lactic Acid/metabolism

KW - Hemodynamics/drug effects

KW - Exenatide/pharmacology

U2 - 10.1097/CCM.0000000000002814

DO - 10.1097/CCM.0000000000002814

M3 - Journal article

C2 - 29189347

VL - 46

SP - E118-E125

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 2

ER -