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


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.


BACKGROUND
NCT00359762, http://www.ClinicalTrials.gov.
CIREDEM, Carlos III Health Institute, Barcelona, Spain. rafael.simo@vhir.org.|Diabetes Research and Metabolism Unit, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain. rafael.simo@vhir.org.
Rafael
R
Simó
Diabetologie, Maladies Metaboliques and Nutrition, Hôpital Brabois, CHU de Nancy, et CIC Inserm, Vandoeuvre Lès Nancy, France. b.guerci@chu-nancy.fr.
Bruno
B
Guerci
Rudolfstiftung Hospital-Vienna, Vienna, Austria. guntram.schernthaner@meduniwien.ac.at.
Guntram
G
Schernthaner
Medizinische Klinik IV, Universitätsklinikum Tübingen, Tübingen, Germany. baptist.gallwitz@med.uni-tuebingen.de.
Baptist
B
Gallwitz
Celaya Center for Specialist Medicine, Celaya, Guanajuato, Mexico. jrosas@att.net.mx.
Juan
J
Rosas-Guzmàn
Diabetes Unit, Policlinico Le Scotte, University of Siena, Siena, Italy. francesco.dotta@alice.it.
Francesco
F
Dotta
Eli Lilly and Company, Eli Lilly Regional Operations Ges.m.b.H., Vienna, Austria. festa_andreas@lilly.com.
Andreas
A
Festa
Bristol-Myers Squibb, Pennington, NJ, USA. ming.zhou@bms.com.
Ming
M
Zhou
Eli Lilly, Eli Lilly and Company, Eli Lilly Polska Sp. z o.o., Warsaw, Poland. kiljanski_jacek@lilly.com.
Jacek
J
Kiljański
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D054795:Incretins / Q000008:administration & dosage* / Q000009:adverse effects; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects
D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D008055:Lipids; D008687:Metformin; D010455:Peptides; D013453:Sulfonylurea Compounds; D014688:Venoms; C517652:hemoglobin A1c protein, human; C057619:glimepiride