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Cited by 47Diabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsHeart Failure Treatment and Management

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

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Simó, Rafael, Guerci, Bruno, Schernthaner, Guntram, Gallwitz, Baptist, Rosas-Guzmàn, Juan, Dotta, Francesco, Festa, Andreas, Zhou, Ming +1 more·2015·Cardiovascular Diabetology
DOI 10.1186/s12933-015-0279-zPMC PMC4558893
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Abstract

OBJECTIVE: The 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 METHODS: 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. Anthropomorphic measures, blood pressure (BP), heart rate, lipids, and high-sensitivity C-reactive protein (hsCRP) over time were evaluated. RESULTS: 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). 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). CONCLUSIONS: Add-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 REGISTRATION: NCT00359762, http://www.ClinicalTrials.gov.

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  • Exenatide showed better anti-inflammatory activity than metformin (SMD = -0.95; 95% CI: -1.78 to -0.13) in spite of metformin's proven pleiotropic advantages.

    “This is clear when compared to metformin (SMD = -0.95; 95% CI: -1.78 to -0.13), where exenatide showed better anti-inflammatory activity in spite of metformin’s proven pleiotropic advantages (13, 19, 38).”

    From Inflammatory biomarker response to GLP-1 receptor agonists versus other glucose-lowering medications in patients with type 2 diabetes: a systematic review and meta-analysis (2026) · cites this paper as [38]

    The Results (hsCRP changes; page not provided) report a greater reduction in hsCRP with exenatide than with glimepiride, both given as add-ons to metformin. The paper does not compare exenatide against metformin or report the cited SMD and confidence interval. The Discussion also says it is unclear whether the hsCRP reduction reflects a drug-specific anti-inflammatory effect. (LLM, conf=0.88)

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References 63 · Cited by 47

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Authors
Simó, R., Guerci, B., Schernthaner, G., Gallwitz, B., Rosas-Guzmàn, J., Dotta, F., Festa, A., Zhou, M., & Kiljański, J.
Affiliations
  • Instituto de Salud Carlos III (ES)
  • Inserm (FR)
  • Krankenanstalt Rudolfstiftung der Stadt Wien (AT)
  • Universitätsklinikum Tübingen (DE)
  • University of Siena (IT)
  • Bristol-Myers Squibb (United States) (US)
Corresponding author
Simó, Rafael
ORCID
Venue
Cardiovascular Diabetology
Publisher
Springer Science and Business Media LLC
Published
2015-09-04
Volume
14
Issue
1
Pages
116-116
ISSN
1475-2840 (ISSN-L)
DOI
10.1186/s12933-015-0279-z
PMC
PMC4558893
OpenAlex
W2139377033
Cited by
47
References
63
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 1 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 14 · 2016: 6
FWCI
7.24
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cardiovascular Diabetology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Use Siena air (University of Siena) (submittedVersion)
Funders
  • Simó
  • Amylin Pharmaceuticals
  • AstraZeneca
  • Bristol-Myers Squibb
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords
exenatide, glimepiride, type 2 diabetes, cardiovascular risk markers, GLP-1 receptor agonists, sulfonylureas, metformin add-on therapy, high-sensitivity C-reactive protein, blood pressure, lipids, body weight, waist circumference, HDL cholesterol, triglycerides, LDL cholesterol, heart rate, antihypertensive drugs
MeSH terms
Exenatide, Aged, Blood Glucose, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Drug Administration Schedule, Drug Therapy, Combination, Europe, Female, Heart Rate, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Lipids, Male, Metformin, Middle Aged, Peptides, Risk Factors, Sulfonylurea Compounds, Time Factors, Venoms, Biomarkers, Treatment Outcome, Incretins

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