Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Blood Glucose/*drug effects ; Cardiovascular Diseases/*chemically induced ; Diabetes Mellitus, Type 2/*drug therapy ; Hypoglycemic Agents/*adverse effects ; Peptides/*adverse effects ; Receptors, Glucagon/*agonists ; Venoms/*adverse effects; Aged ; Biomarkers/blood ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/blood ; Evidence-Based Medicine ; Exenatide ; Female ; Glucagon-Like Peptide-1 Receptor ; Glycated Hemoglobin/metabolism ; Humans ; Hypoglycemic Agents/administration & dosage ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Peptides/administration & dosage ; Proportional Hazards Models ; Randomized Controlled Trials as Topic ; Receptors, Glucagon/metabolism ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Venoms/administration & dosage

Unlabelled: It is important for patients that treatments for diabetes not increase cardiovascular (CV) risk. The objective of this analysis was to examine retrospectively the CV safety of exenatide BID, a GLP-1 receptor agonist approved for treating hyperglycemia in patients with type 2 diabetes not adequately controlled with diet and exercise. Individual participant data was pooled to assess the relative risk (RR) of CV events with exenatide BID versus a pooled comparator (PC) group treated with either placebo or insulin from 12 controlled, randomized, clinical trials ranging from 12-52 weeks. Mean baseline values for HbA1c (8.33-8.38%), BMI (31.3-31.5 kg/m2), and duration of diabetes (8 y) were similar between groups. Trials included patients with histories of microvascular and/or macrovascular disease. Customized primary major adverse CV events (MACE) included stroke, myocardial infarction, cardiac mortality, acute coronary syndrome, and revascularization procedures. The Primary MACE RR (0.7; 95% CI 0.38, 1.31), calculated by the Mantel-Haenszel method (stratified by study), suggested that exenatide use (vs. PC) did not increase CV risk; this result was consistent across multiple analytic methods. Because the trials were not designed to assess CV outcomes, events were identified retrospectively from a list of preferred terms by physicians blinded to treatment. Other limitations included the low number of CV events, the short duration of trials (≤1 y), and a single active comparator (insulin). The results of these analyses are consistent with those of a recent retrospective analysis of a large insurance database that found that patients treated with exenatide twice daily were less likely to have a CV event than were patients treated with other glucose-lowering therapies.
Keywords: GLP-1 receptor agonist, diabetes, cardiovascular safety.

Diabetes Care. 2007 Jan;30(1):162-72. (PMID: 17192355)
Drug Saf. 2010 Feb 1;33(2):87-100. (PMID: 20082536)
Ann Intern Med. 2009 Sep 15;151(6):394-403. (PMID: 19620144)
Expert Opin Drug Saf. 2009 Sep;8(5):573-84. (PMID: 19538102)
BMJ. 1998 Sep 12;317(7160):713-20. (PMID: 9732338)
N Engl J Med. 2009 Jan 8;360(2):129-39. (PMID: 19092145)
Lancet. 2009 Jun 20;373(9681):2125-35. (PMID: 19501900)
Endocr Pract. 2009 Sep-Oct;15(6):540-59. (PMID: 19858063)
N Engl J Med. 1993 Sep 30;329(14):977-86. (PMID: 8366922)
Lancet. 2007 Sep 29;370(9593):1103-4. (PMID: 17905146)
Ann Intern Med. 2004 Sep 21;141(6):421-31. (PMID: 15381515)
Diabetes Care. 2010 May;33(5):983-90. (PMID: 20427682)
Diabetes Care. 2005 May;28(5):1083-91. (PMID: 15855571)
J Card Fail. 2006 Dec;12(9):694-9. (PMID: 17174230)
BMJ. 2010 Jan 08;340:b4909. (PMID: 20061358)
Stat Med. 2005 Mar 30;24(6):955-65. (PMID: 15532090)
N Engl J Med. 2005 Dec 22;353(25):2643-53. (PMID: 16371630)
Diabetes Care. 2004 Nov;27(11):2628-35. (PMID: 15504997)
Stat Med. 2007 Oct 30;26(24):4375-85. (PMID: 17768699)
Diabetologia. 2007 Feb;50(2):259-67. (PMID: 17160407)
Eur Heart J. 2010 Dec;31(24):3040-5. (PMID: 20935002)
Diabetes Obes Metab. 2006 Jul;8(4):419-28. (PMID: 16776749)
Perspect Biol Med. 2004 Autumn;47(4):564-74. (PMID: 15467178)
Diabetes Care. 2011 Jan;34(1):90-5. (PMID: 20929995)
JAMA. 2010 Jul 28;304(4):411-8. (PMID: 20584880)
Lancet. 1998 Sep 12;352(9131):837-53. (PMID: 9742976)
J Intern Med. 1999 Sep;246(3):299-307. (PMID: 10475998)
Diabet Med. 1997 Aug;14(8):648-54. (PMID: 9272590)
Atherosclerosis. 2010 Sep;212(1):223-9. (PMID: 20494360)
Ann Intern Med. 2007 Apr 3;146(7):477-85. (PMID: 17404349)
Arch Intern Med. 2010 Jul 26;170(14):1191-1201. (PMID: 20656674)
JAMA. 2010 Mar 24;303(12):1194-5. (PMID: 20332408)
JAMA. 2010 Jul 28;304(4):469-71. (PMID: 20584879)
Cardiovasc Diabetol. 2010 Jan 28;9:6. (PMID: 20109208)
Curr Med Res Opin. 2008 Jan;24(1):275-86. (PMID: 18053320)
Am J Hypertens. 1996 Apr;9(4 Pt 1):342-60. (PMID: 8722437)
N Engl J Med. 2008 Jun 12;358(24):2545-59. (PMID: 18539917)
Diabetes Obes Metab. 2006 Jul;8(4):436-47. (PMID: 16776751)
N Engl J Med. 2007 Jun 14;356(24):2457-71. (PMID: 17517853)
Diabetes Metab. 2010 Nov;36(5):381-8. (PMID: 20598606)
N Engl J Med. 2007 Jun 14;356(24):2522-4. (PMID: 17517854)
Lancet. 1998 Sep 12;352(9131):854-65. (PMID: 9742977)
J Pharmacol Exp Ther. 2006 Jun;317(3):1106-13. (PMID: 16489128)
Am J Hypertens. 2010 Mar;23(3):334-9. (PMID: 20019672)
Lancet. 1994 Nov 19;344(8934):1383-9. (PMID: 7968073)
Am J Epidemiol. 1990 Feb;131(2):373-5. (PMID: 2296988)
Diabetes Care. 2010 Feb;33(2):428-33. (PMID: 20103558)
Diabetes Care. 2007 Nov;30(11):2767-72. (PMID: 17595353)
Clin Ther. 2007 Nov;29(11):2333-48. (PMID: 18158075)
Circulation. 2004 Aug 24;110(8):955-61. (PMID: 15313949)
Circulation. 2004 Mar 2;109(8):962-5. (PMID: 14981009)
N Engl J Med. 2010 Aug 26;363(9):803-6. (PMID: 20660395)
Diabetes Care. 2005 May;28(5):1092-100. (PMID: 15855572)
N Engl J Med. 2010 Mar 4;362(9):774-7. (PMID: 20164475)
Diabetologia. 2009 Jan;52(1):65-73. (PMID: 18985314)
Lancet. 2009 Jul 4;374(9683):39-47. (PMID: 19515413)
Diabetes Care. 2010 Aug;33(8):1734-7. (PMID: 20424219)
Ann Intern Med. 2007 Oct 16;147(8):585-7. (PMID: 17938398)
Diabetes Care. 2008 Jan;31(1):173-5. (PMID: 18165348)
Ann Intern Med. 2005 Oct 18;143(8):559-69. (PMID: 16230722)
BMJ. 2000 Aug 12;321(7258):405-12. (PMID: 10938048)
Ann Intern Med. 2007 Oct 16;147(8):578-81. (PMID: 17679700)
Diabetes Res Clin Pract. 2009 Jan;83(1):69-76. (PMID: 19019476)
N Engl J Med. 2008 Feb 7;358(6):580-91. (PMID: 18256393)
Diabetes. 2005 Jan;54(1):146-51. (PMID: 15616022)
Clin Ther. 2008 Aug;30(8):1448-60. (PMID: 18803987)
N Engl J Med. 2008 Oct 9;359(15):1577-89. (PMID: 18784090)
Diabetes Care. 1997 Nov;20(11):1744-66. (PMID: 9353619)
Endocr J. 2009;56(3):415-24. (PMID: 19194050)
Cardiovasc Diabetol. 2010 Nov 16;9:76. (PMID: 21080957)
J Diabetes Sci Technol. 2010 Nov 01;4(6):1516-23. (PMID: 21129350)
Diabetologia. 2007 Jan;50(1):186-94. (PMID: 17096116)
Am J Cardiol. 2003 Jul 3;92(1A):3i-9i. (PMID: 12867249)
N Engl J Med. 2008 Jun 12;358(24):2560-72. (PMID: 18539916)
Cardiovasc Diabetol. 2010 Aug 03;9:32. (PMID: 20678234)
BMJ. 1998 Sep 12;317(7160):703-13. (PMID: 9732337)

0 (Biomarkers)
0 (Blood Glucose)
0 (GLP1R protein, human)
0 (Glucagon-Like Peptide-1 Receptor)
0 (Glycated Hemoglobin A)
0 (Hypoglycemic Agents)
0 (Peptides)
0 (Receptors, Glucagon)
0 (Venoms)
0 (hemoglobin A1c protein, human)
9P1872D4OL (Exenatide)

Date Created: 20110318 Date Completed: 20110617 Latest Revision: 20221207

20231215

PMC3070629

10.1186/1475-2840-10-22

21410975