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Study · Not a test of the peptide alone · 2019

6 results

Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes: insights from the EXSCEL trial.

Clegg LE, Penland RC, Bachina S, Boulton DW, Thuresson M, Heerspink HJL, Gustavson S, Sjöström CD, Ruggles JA, Hernandez AF, Buse JB, Mentz RJ, Holman RR

Cardiovascular diabetology22 Oct 2019Cited by 70 (Europe PMC)

PMID31640705 (opens in a new tab)PMCIDPMC6805385 (opens in a new tab)DOI10.1186/s12933-019-0942-x (opens in a new tab)PepBankPUB-31640705
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Summary

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct mechanisms. However, evidence on clinical outcomes in patients treated with both GLP-1 RA and SGLT2i is lacking. We aim to provide insight into the effects of open-label SGLT2i use in parallel with or shortly after once-weekly GLP-1 RA exenatide (EQW) on cardiorenal outcomes.MethodsIn the EXSCEL cardiovascular outcomes trial EQW arm, SGLT2i drop-in occurred in 8.7% of participants. These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups. Time-to-first major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR slopes were quantified using mixed model repeated measurement analyses.ResultsIn adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39-1.17) and EQW alone (0.85, 0.48-1.49). Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16-0.90) and compared with EQW (0.41, 0.17-0.95). Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94-2.94 mL/min/1.73 m2/year) and EQW alone (+ 2.38, 1.40-3.35 mL/min/1.73 m2/year).ConclusionsThis post hoc analysis supports the hypothesis that combinatorial EQW and SGLT2i therapy may provide benefit on cardiovascular outcomes and mortality. Trial registration Clinicaltrials.gov, Identifying number: NCT01144338, Date of registration: June 15, 2010.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

  1. 01HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome

    In type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to numerically lower MACE risk versus exenatide alone, without statistical significance.

    In plain wordsIn type 2 diabetes, combination use was linked to numerically lower heart event risk versus exenatide alone, without statistical significance.

    Peptide
    Exenatide (exendin-4)
    Outcome
    No significant changeMACE versus exenatide alone
    Study

    n = 1,150

    Comparator
    Exenatide alone
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    Adjusted hazard ratio
    0.85 ratio
    versus exenatide alone

    Source sentences

    Summary
    In adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39-1.17) and EQW alone (0.85, 0.48-1.49).
    1 context sentence
    Summary · context
    These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups.

    In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).

  2. 02HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome

    In type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally lower mortality versus exenatide alone.

    In plain wordsIn type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally lower mortality versus exenatide alone.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseAll-cause mortality versus exenatide alone
    Study

    n = 1,150

    Comparator
    Exenatide alone
    Outcome group
    Mortality · Whole body

    Measurements

    Hazard ratio
    0.41 ratio
    versus exenatide

    Source sentences

    Summary
    Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16-0.90) and compared with EQW (0.41, 0.17-0.95).
    1 context sentence
    Summary · context
    These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups.

    In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).

  3. 03HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome

    In type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally improved eGFR slope versus exenatide alone.

    In plain wordsIn type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally improved kidney filtration slope versus exenatide alone.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseeGFR slope versus exenatide alone
    Study

    n = 1,150

    Comparator
    Exenatide alone
    Outcome group
    Kidney function · Kidney and urinary

    Measurements

    eGFR slope difference
    2.38 mL/min/1.73 m²/year
    versus exenatide

    Source sentences

    Summary
    Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94-2.94 mL/min/1.73 m2/year) and EQW alone (+ 2.38, 1.40-3.35 mL/min/1.73 m2/year).
    1 context sentence
    Summary · context
    These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups.

    In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).

  4. 04HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome

    In type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to numerically lower MACE risk versus placebo, without statistical significance.

    In plain wordsIn type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to numerically lower heart event risk versus placebo, without statistical significance.

    Peptide
    Exenatide (exendin-4)
    Outcome
    No significant changeMACE versus placebo
    Study

    n = 1,144

    Comparator
    Placebo without SGLT2 inhibitor
    Outcome group
    Cardiovascular events · Cardiovascular

    Measurements

    Adjusted hazard ratio
    0.68 ratio
    versus placebo

    Source sentences

    Summary
    In adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39-1.17) and EQW alone (0.85, 0.48-1.49).
    1 context sentence
    Summary · context
    These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups.

    In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).

  5. 05HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome

    In type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally lower mortality versus placebo.

    In plain wordsIn type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally lower mortality versus placebo.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseAll-cause mortality versus placebo
    Study

    n = 1,144

    Comparator
    Placebo without SGLT2 inhibitor
    Outcome group
    Mortality · Whole body

    Measurements

    Hazard ratio
    0.38 ratio
    versus placebo

    Source sentences

    Summary
    Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16-0.90) and compared with EQW (0.41, 0.17-0.95).
    1 context sentence
    Summary · context
    These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups.

    In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).

  6. 06HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome

    In type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally improved eGFR slope versus placebo.

    In plain wordsIn type 2 diabetes, exenatide plus SGLT2 inhibitor use was linked to nominally improved kidney filtration slope versus placebo.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseeGFR slope versus placebo
    Study

    n = 1,144

    Comparator
    Placebo without SGLT2 inhibitor
    Outcome group
    Kidney function · Kidney and urinary

    Measurements

    eGFR slope difference
    1.94 mL/min/1.73 m²/year
    versus placebo

    Source sentences

    Summary
    Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94-2.94 mL/min/1.73 m2/year) and EQW alone (+ 2.38, 1.40-3.35 mL/min/1.73 m2/year).
    1 context sentence
    Summary · context
    These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups.

    In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT01144338

Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus

AstraZenecan = 14,75218 Jun 2010 to 24 Apr 2017

Type 2 Diabetes Mellitus

Trial pageClinicalTrials.govUpdated 8 Aug 2018

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.

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