Long-term changes in cardiovascular risk markers during administration of exenatide twice daily or glimepiride: results from the European exenatide study.

Simó R, Guerci B, Schernthaner G, Gallwitz B, Rosas-Guzmàn J, Dotta F, Festa A, Zhou M, Kiljański J

Cardiovascular diabetology4 Sept 2015Cited by 44 (Europe PMC)

PMID26338040PMCIDPMC4558893DOI10.1186/s12933-015-0279-zPepBankPUB-26338040

Summary

ObjectiveThe risk of cardiovascular morbidity and mortality is significantly increased in patients with diabetes; thus, it is important to determine whether glucose-lowering therapy affects this risk over time. Changes in cardiovascular risk markers were examined in patients with type 2 diabetes treated with exenatide twice daily (a glucagon-like peptide-1 receptor agonist) or glimepiride (a sulfonylurea) added to metformin in the EURopean EXenAtide (EUREXA) study.Research design and methodsPatients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C. Anthropomorphic measures, blood pressure (BP), heart rate, lipids, and high-sensitivity C-reactive protein (hsCRP) over time were evaluated.ResultsOver 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L). Heart rate did not increase (-0.3 beats/minute), and low-density lipoprotein-cholesterol (0.2 mmol/L) and total cholesterol (0.1 mmol/L) increased slightly. Between-group differences were significantly in favor of exenatide for body weight (P < 0.0001), waist circumference (P < 0.001), systolic BP (P < 0.001), diastolic BP (P = 0.023), HDL-cholesterol (P = 0.001), and hsCRP (P = 0.004). Fewer patients randomized to exenatide twice daily versus glimepiride required the addition of at least one antihypertensive (20.4 vs 26.4%; P = 0.026) or lipid-lowering medication (8.4 vs 12.8%; P = 0.025).ConclusionsAdd-on exenatide twice daily was associated with significant, sustained improvement in several cardiovascular risk markers in patients with type 2 diabetes versus glimepiride.Clinical trial registrationNCT00359762, http://www.ClinicalTrials.gov.

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

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, exenatide reduced body weight more than glimepiride.
In plain wordsIn diabetes treated with metformin, exenatide reduced weight more than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseBody weight
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Weight change
−3.9 kg
exenatide
Source sentences
Summary
Between-group differences were significantly in favor of exenatide for body weight (P < 0.0001), waist circumference (P < 0.001), systolic BP (P < 0.001), diastolic BP (P = 0.023), HDL-cholesterol (P = 0.001), and hsCRP (P = 0.004).
2 context sentences(design, population, supporting numbers)
Summary · context
Over 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L).
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804001
02HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, exenatide reduced waist circumference more than glimepiride.
In plain wordsIn diabetes treated with metformin, exenatide reduced waist size more than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseWaist circumference
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Waist change
−3.6 cm
exenatide
Source sentences
Summary
Between-group differences were significantly in favor of exenatide for body weight (P < 0.0001), waist circumference (P < 0.001), systolic BP (P < 0.001), diastolic BP (P = 0.023), HDL-cholesterol (P = 0.001), and hsCRP (P = 0.004).
2 context sentences(design, population, supporting numbers)
Summary · context
Over 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L).
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804002
03HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, exenatide reduced systolic blood pressure more than glimepiride.
In plain wordsIn diabetes treated with metformin, exenatide reduced systolic blood pressure more than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseSystolic blood pressure
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Systolic BP change
−2.5 mmHg
exenatide
Source sentences
Summary
Between-group differences were significantly in favor of exenatide for body weight (P < 0.0001), waist circumference (P < 0.001), systolic BP (P < 0.001), diastolic BP (P = 0.023), HDL-cholesterol (P = 0.001), and hsCRP (P = 0.004).
2 context sentences(design, population, supporting numbers)
Summary · context
Over 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L).
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804003
04HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, exenatide reduced diastolic blood pressure more than glimepiride.
In plain wordsIn diabetes treated with metformin, exenatide reduced diastolic blood pressure more than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseDiastolic blood pressure
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Diastolic BP change
−2.6 mmHg
exenatide
Source sentences
Summary
Between-group differences were significantly in favor of exenatide for body weight (P < 0.0001), waist circumference (P < 0.001), systolic BP (P < 0.001), diastolic BP (P = 0.023), HDL-cholesterol (P = 0.001), and hsCRP (P = 0.004).
2 context sentences(design, population, supporting numbers)
Summary · context
Over 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L).
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804004
05HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, exenatide improved HDL cholesterol more than glimepiride.
In plain wordsIn diabetes treated with metformin, exenatide improved HDL cholesterol more than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseHDL cholesterol
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Lipids · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
HDL change
0.05 mmol/L
exenatide
Source sentences
Summary
Between-group differences were significantly in favor of exenatide for body weight (P < 0.0001), waist circumference (P < 0.001), systolic BP (P < 0.001), diastolic BP (P = 0.023), HDL-cholesterol (P = 0.001), and hsCRP (P = 0.004).
2 context sentences(design, population, supporting numbers)
Summary · context
Over 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L).
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804005
06HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, exenatide reduced hsCRP more than glimepiride.
In plain wordsIn diabetes treated with metformin, exenatide reduced the inflammation marker hsCRP more than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseHigh-sensitivity C-reactive protein
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
hsCRP change
−1.7 mg/L
exenatide
Source sentences
Summary
Between-group differences were significantly in favor of exenatide for body weight (P < 0.0001), waist circumference (P < 0.001), systolic BP (P < 0.001), diastolic BP (P = 0.023), HDL-cholesterol (P = 0.001), and hsCRP (P = 0.004).
2 context sentences(design, population, supporting numbers)
Summary · context
Over 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L).
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804007
07HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, fewer exenatide patients than glimepiride patients needed additional antihypertensive medication.
In plain wordsIn diabetes treated with metformin, fewer patients needed added blood pressure medication with exenatide than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdditional antihypertensive medication
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Requiring antihypertensive
20.4%
exenatide
Requiring antihypertensive
26.4%
glimepiride
Source sentences
Summary
Fewer patients randomized to exenatide twice daily versus glimepiride required the addition of at least one antihypertensive (20.4 vs 26.4%; P = 0.026) or lipid-lowering medication (8.4 vs 12.8%; P = 0.025).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804011
08HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, fewer exenatide patients than glimepiride patients needed additional lipid-lowering medication.
In plain wordsIn diabetes treated with metformin, fewer patients needed added cholesterol medication with exenatide than glimepiride.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseAdditional lipid-lowering medication
Study
n = 1,029
Comparator
Glimepiride
Outcome group
Lipids · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Requiring lipid-lowering medication
8.4%
exenatide
Requiring lipid-lowering medication
12.8%
glimepiride
Source sentences
Summary
Fewer patients randomized to exenatide twice daily versus glimepiride required the addition of at least one antihypertensive (20.4 vs 26.4%; P = 0.026) or lipid-lowering medication (8.4 vs 12.8%; P = 0.025).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804012
09HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, triglycerides decreased during exenatide treatment.
In plain wordsIn diabetes treated with metformin, triglycerides decreased during exenatide treatment.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseTriglycerides
Study
n = 515
Outcome group
Lipids · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Triglyceride change
−0.2 mmol/L
exenatide
Source sentences
Summary
Over 36 months, twice-daily exenatide was associated with improved body weight (-3.9 kg), waist circumference (-3.6 cm), systolic/diastolic BP (-2.5/-2.6 mmHg), high-density lipoprotein (HDL)-cholesterol (0.05 mmol/L), triglycerides (-0.2 mmol/L), and hsCRP (-1.7 mg/L).
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804006
10HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, heart rate did not increase during exenatide treatment.
In plain wordsIn diabetes treated with metformin, heart rate did not increase during exenatide treatment.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeHeart rate
Study
n = 515
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Heart rate change
−0.3 beats/minute
exenatide
Source sentences
Summary
Heart rate did not increase (-0.3 beats/minute), and low-density lipoprotein-cholesterol (0.2 mmol/L) and total cholesterol (0.1 mmol/L) increased slightly.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804008
11HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, LDL cholesterol increased slightly during exenatide treatment.
In plain wordsIn diabetes treated with metformin, LDL cholesterol increased slightly during exenatide treatment.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseLDL cholesterol
Study
n = 515
Outcome group
Lipids · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
LDL change
0.2 mmol/L
exenatide
Source sentences
Summary
Heart rate did not increase (-0.3 beats/minute), and low-density lipoprotein-cholesterol (0.2 mmol/L) and total cholesterol (0.1 mmol/L) increased slightly.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804009
12HumanRandomized controlled trialEfficacy outcome
In diabetes treated with metformin, total cholesterol increased slightly during exenatide treatment.
In plain wordsIn diabetes treated with metformin, total cholesterol increased slightly during exenatide treatment.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseTotal cholesterol
Study
n = 515
Outcome group
Lipids · Cardiovascular
Studied dose
Dose not stated · 36 monthsAs given in this study (human).
Measurements
Total cholesterol change
0.1 mmol/L
exenatide
Source sentences
Summary
Heart rate did not increase (-0.3 beats/minute), and low-density lipoprotein-cholesterol (0.2 mmol/L) and total cholesterol (0.1 mmol/L) increased slightly.
1 context sentence(design, population, supporting numbers)
Summary · context
Patients with type 2 diabetes failing metformin were randomized to add-on exenatide twice daily (n = 515) or glimepiride (n = 514) until treatment failure defined by hemoglobin A1C.
Show in the study text Report a problemFND-2633804010

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 postedNCT00359762

Exenatide Versus Glimepiride in Patients With Type 2 Diabetes

AstraZenecan = 1,029Sept 2006 to Mar 2011

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 15 Sept 2015

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

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