The association of the treatment with glucagon-like peptide-1 receptor agonist exenatide or insulin with cardiovascular outcomes in patients with type 2 diabetes: a retrospective observational study.

Paul SK, Klein K, Maggs D, Best JH

Cardiovascular diabetology24 Jan 2015Cited by 45 (Europe PMC)

PMID25616979PMCIDPMC4314769DOI10.1186/s12933-015-0178-3PepBankPUB-25616979

Summary

BackgroundTo evaluate the association of treatment with glucagon-like peptide-1 (GLP-1) receptor agonist exenatide and/or insulin on macrovascular outcomes in patients with type 2 diabetes (T2DM).MethodsWe conducted a retrospective longitudinal pharmaco-epidemiological study using large ambulatory care data to evaluate the risks of heart failure (HF), myocardial infarction (MI) and stroke in established T2DM patients who received a first prescription of exenatide twice daily (EBID) or insulin between June 2005 and May 2009, with follow-up data available until December 2012. Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870). Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.ResultsDuring a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1). Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).ConclusionsTreatment with exenatide, with or without concomitant insulin was associated with reduced macrovascular risks compared to insulin; although inherent potential bias in epidemiological studies should be considered.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

6 results from studies that gave the peptide. 6 results from people.

01HumanObservational studyEfficacy outcome
In T2DM records, exenatide with oral drugs was linked to lower heart failure event rates than insulin with oral drugs.
In plain wordsIn diabetes records, exenatide with oral drugs was linked to fewer heart failure events than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseHeart failure event rate
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
HF event rate
4.4 per 1000 person-years
EBID
HF event rate
17.9 per 1000 person-years
insulin
Source sentences
Summary
During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
Show in the study text Report a problemFND-2561697901
02HumanObservational studyEfficacy outcome
In T2DM records, exenatide with oral drugs was linked to lower myocardial infarction rates than insulin with oral drugs.
In plain wordsIn diabetes records, exenatide with oral drugs was linked to fewer heart attacks than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseMyocardial infarction event rate
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
MI event rate
1.1 per 1000 person-years
EBID
MI event rate
2.5 per 1000 person-years
insulin
Source sentences
Summary
During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
Show in the study text Report a problemFND-2561697903
03HumanObservational studyEfficacy outcome
In T2DM records, exenatide with oral drugs was linked to lower stroke rates than insulin with oral drugs.
In plain wordsIn diabetes records, exenatide with oral drugs was linked to fewer strokes than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseStroke event rate
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
stroke event rate
2.4 per 1000 person-years
EBID
stroke event rate
6.1 per 1000 person-years
insulin
Source sentences
Summary
During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
Show in the study text Report a problemFND-2561697905
04HumanObservational studyEfficacy outcome
In T2DM records, exenatide with oral drugs was linked to lower adjusted heart failure risk than insulin with oral drugs.
In plain wordsIn diabetes records, exenatide with oral drugs was linked to lower heart failure risk than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdjusted heart failure risk
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
HF risk reduction
61%
EBID versus insulin
Source sentences
Summary
Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
Show in the study text Report a problemFND-2561697907
05HumanObservational studyEfficacy outcome
In T2DM records, exenatide with oral drugs was linked to lower adjusted myocardial infarction risk than insulin with oral drugs.
In plain wordsIn diabetes records, exenatide with oral drugs was linked to lower heart attack risk than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdjusted myocardial infarction risk
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
MI risk reduction
50%
EBID versus insulin
Source sentences
Summary
Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
Show in the study text Report a problemFND-2561697909
06HumanObservational studyEfficacy outcome
In T2DM records, exenatide with oral drugs was linked to lower adjusted stroke risk than insulin with oral drugs.
In plain wordsIn diabetes records, exenatide with oral drugs was linked to lower stroke risk than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdjusted stroke risk
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
stroke risk reduction
52%
EBID versus insulin
Source sentences
Summary
Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
Show in the study text Report a problemFND-2561697911

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).

07HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome
In T2DM records, mixed exenatide/insulin exposure with oral drugs was linked to lower heart failure rates than insulin with oral drugs.
In plain wordsIn diabetes records, mixed exenatide/insulin exposure was linked to fewer heart failure events than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseHeart failure event rate with mixed exposure
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HF event rate
6.1 per 1000 person-years
EBID + insulin
HF event rate
17.9 per 1000 person-years
insulin
Source sentences
Summary
During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
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).
Show in the study text Report a problemFND-2561697902
08HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome
In T2DM records, mixed exenatide/insulin exposure with oral drugs was linked to lower myocardial infarction rates than insulin with oral drugs.
In plain wordsIn diabetes records, mixed exenatide/insulin exposure was linked to fewer heart attacks than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseMyocardial infarction rate with mixed exposure
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Measurements
MI event rate
1.2 per 1000 person-years
EBID + insulin
MI event rate
2.5 per 1000 person-years
insulin
Source sentences
Summary
During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
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).
Show in the study text Report a problemFND-2561697904
09HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome
In T2DM records, mixed exenatide/insulin exposure with oral drugs was linked to lower stroke rates than insulin with oral drugs.
In plain wordsIn diabetes records, mixed exenatide/insulin exposure was linked to fewer strokes than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseStroke rate with mixed exposure
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Measurements
stroke event rate
1.8 per 1000 person-years
EBID + insulin
stroke event rate
6.1 per 1000 person-years
insulin
Source sentences
Summary
During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
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).
Show in the study text Report a problemFND-2561697906
10HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome
In T2DM records, mixed exenatide/insulin exposure was linked to lower adjusted heart failure risk than insulin with oral drugs.
In plain wordsIn diabetes records, mixed exenatide/insulin exposure was linked to lower heart failure risk than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdjusted heart failure risk with mixed exposure
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HF risk reduction
56%
EBID + insulin versus insulin
Source sentences
Summary
Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
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).
Show in the study text Report a problemFND-2561697908
11HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome
In T2DM records, mixed exenatide/insulin exposure was linked to lower adjusted myocardial infarction risk than insulin with oral drugs.
In plain wordsIn diabetes records, mixed exenatide/insulin exposure was linked to lower heart attack risk than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdjusted myocardial infarction risk with mixed exposure
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Measurements
MI risk reduction
38%
EBID + insulin versus insulin
Source sentences
Summary
Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
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).
Show in the study text Report a problemFND-2561697910
12HumanNot a test of Exenatide (exendin-4) aloneObservational studyEfficacy outcome
In T2DM records, mixed exenatide/insulin exposure was linked to lower adjusted stroke risk than insulin with oral drugs.
In plain wordsIn diabetes records, mixed exenatide/insulin exposure was linked to lower stroke risk than insulin with oral drugs.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdjusted stroke risk with mixed exposure
Study
n: not reported in source
Comparator
insulin with oral antidiabetes drugs
Outcome group
Cardiovascular events · Cardiovascular
Measurements
stroke risk reduction
63%
EBID + insulin versus insulin
Source sentences
Summary
Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01).
2 context sentences(design, population, supporting numbers)
Summary · context
Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870).
Summary · context
Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events.
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).
Show in the study text Report a problemFND-2561697912

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.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
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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