Skip to content

Study · Randomized controlled trial · 2013

4 results

Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects.

Darpö B, Sager P, MacConell L, Cirincione B, Mitchell M, Han J, Huang W, Malloy J, Schulteis C, Shen L, Porter L

British journal of clinical pharmacology1 Apr 2013Cited by 30 (Europe PMC)

PMID22882281 (opens in a new tab)PMCIDPMC3612716 (opens in a new tab)DOI10.1111/j.1365-2125.2012.04416.x (opens in a new tab)PepBankPUB-22882281
Download PDFPubMedAsk about this study
Jump to 4 results

Summary

AimsExenatide has been demonstrated to improve glycaemic control in patients with type 2 diabetes, with no effect on heart rate corrected QT (QTc ) at therapeutic concentrations. This randomized, placebo- and positive-controlled, crossover, thorough QT study evaluated the effects of therapeutic and supratherapeutic exenatide concentrations on QTc .MethodsIntravenous infusion was employed to achieve steady-state supratherapeutic concentrations in healthy subjects within a reasonable duration (i.e. days). Subjects received exenatide, placebo and moxifloxacin, with ECGs recorded pre-therapy and during treatment. Intravenous exenatide was expected to increase heart rate to a greater extent than subcutaneous twice daily or once weekly formulations. To assure proper heart rate correction, a wide range of baseline heart rates was assessed and prospectively defined methodology was applied to determine the optimal QT correction.ResultsTargeted steady-state plasma exenatide concentrations were exceeded (geometric mean ± SEM 253 ± 8.5 pg ml(-1) , 399 ± 11.9 pg ml(-1) and 627 ± 21.2 pg ml(-1) ). QTc P, a population-based method, was identified as the most appropriate heart rate correction and was prespecified for primary analysis. The upper bound of the two-sided 90% confidence interval for placebo-corrected, baseline-adjusted QTc P (ΔΔQTc P) was <10 ms at all time points and exenatide concentrations. The mean of three measures assessed at the highest steady-state plasma exenatide concentration of ∼500 pg ml(-1) (ΔΔQTc P(avg) ) was -1.13 [-2.11, -0.15). No correlation was observed between ΔΔQTc P and exenatide concentration. Assay sensitivity was confirmed with moxifloxacin.ConclusionsThese results demonstrated that exenatide, at supratherapeutic concentrations, does not prolong QTc and provide an example of methodology for QT assessment of drugs with an inherent heart rate effect.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

  1. 01HumanRandomized controlled trialSafety outcome

    In healthy subjects, the upper confidence bound for placebo-corrected QTc P remained below 10 ms at all exenatide concentrations.

    In plain wordsIn healthy people, exenatide did not prolong corrected heart electrical timing compared with placebo.

    Peptide
    Exenatide (exendin-4)
    Outcome
    No significant changePlacebo-corrected QTc P
    Study

    n: not reported in source

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · intravenousAs given in this study (human).

    Measurements

    Upper bound of 90% CI, placebo-corrected baseline-adjusted QTcP
    < 10 ms
    all time points and exenatide concentrations

    Source sentences

    Summary
    The upper bound of the two-sided 90% confidence interval for placebo-corrected, baseline-adjusted QTc P (ΔΔQTc P) was <10 ms at all time points and exenatide concentrations.
    3 context sentences
    Summary · context
    QTc P, a population-based method, was identified as the most appropriate heart rate correction and was prespecified for primary analysis.
    Summary · context
    This randomized, placebo- and positive-controlled, crossover, thorough QT study evaluated the effects of therapeutic and supratherapeutic exenatide concentrations on QTc .
    Summary · context
    Intravenous infusion was employed to achieve steady-state supratherapeutic concentrations in healthy subjects within a reasonable duration (i.e. days).
  2. 02HumanRandomized controlled trialPharmacokinetics

    In healthy subjects, intravenous exenatide exceeded targeted steady-state plasma concentrations.

    In plain wordsIn healthy people, intravenous exenatide reached concentrations above the targets.

    Peptide
    Exenatide (exendin-4)
    Outcome
    Not applicableSteady-state plasma concentrations
    Study

    n: not reported in source

    Outcome group
    Pharmacokinetics · Pharmacology
    Studied dose
    Dose not stated · intravenousAs given in this study (human).

    Measurements

    Geometric mean plasma concentration
    253 pg ml(-1)
    first concentration level
    Geometric mean plasma concentration
    399 pg ml(-1)
    second concentration level
    Geometric mean plasma concentration
    627 pg ml(-1)
    third concentration level

    Source sentences

    Summary
    Targeted steady-state plasma exenatide concentrations were exceeded (geometric mean ± SEM 253 ± 8.5 pg ml(-1) , 399 ± 11.9 pg ml(-1) and 627 ± 21.2 pg ml(-1) ).
    2 context sentences
    Summary · context
    This randomized, placebo- and positive-controlled, crossover, thorough QT study evaluated the effects of therapeutic and supratherapeutic exenatide concentrations on QTc .
    Summary · context
    Intravenous infusion was employed to achieve steady-state supratherapeutic concentrations in healthy subjects within a reasonable duration (i.e. days).
  3. 03HumanRandomized controlled trialSafety outcome

    In healthy subjects, mean placebo-corrected QTc P at the highest steady-state exenatide concentration was -1.13.

    In plain wordsIn healthy people, average corrected heart electrical timing was slightly shorter with exenatide than placebo at the highest concentration.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseAverage QTc P at highest concentration
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · intravenousAs given in this study (human).

    Measurements

    Mean ΔΔQTcP(avg)
    −1.13
    highest steady-state exenatide concentration ~500 pg/ml
    Interval for ΔΔQTcP(avg)
    −2.11 to −0.15
    highest steady-state exenatide concentration ~500 pg/ml

    Source sentences

    Summary
    The mean of three measures assessed at the highest steady-state plasma exenatide concentration of ∼500 pg ml(-1) (ΔΔQTc P(avg) ) was -1.13 [-2.11, -0.15).
    2 context sentences
    Summary · context
    This randomized, placebo- and positive-controlled, crossover, thorough QT study evaluated the effects of therapeutic and supratherapeutic exenatide concentrations on QTc .
    Summary · context
    Intravenous infusion was employed to achieve steady-state supratherapeutic concentrations in healthy subjects within a reasonable duration (i.e. days).
  4. 04HumanRandomized controlled trialSafety outcome

    In healthy subjects, placebo-corrected QTc P did not correlate with exenatide concentration.

    In plain wordsIn healthy people, corrected heart electrical timing did not correlate with exenatide concentration.

    Peptide
    Exenatide (exendin-4)
    Outcome
    No significant changeQTc P concentration relationship
    Study

    n: not reported in source

    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · intravenousAs given in this study (human).

    Source sentences

    Summary
    No correlation was observed between ΔΔQTc P and exenatide concentration.
    2 context sentences
    Summary · context
    This randomized, placebo- and positive-controlled, crossover, thorough QT study evaluated the effects of therapeutic and supratherapeutic exenatide concentrations on QTc .
    Summary · context
    Intravenous infusion was employed to achieve steady-state supratherapeutic concentrations in healthy subjects within a reasonable duration (i.e. days).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.