Table of Contents Author Guidelines Submit a Manuscript
Experimental Diabetes Research
Volume 2011, Article ID 215764, 10 pages
http://dx.doi.org/10.1155/2011/215764
Research Article

Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Events: A Meta-Analysis of Randomized Clinical Trials

1Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, University of Florence and Careggi Teaching Hospital, 50141 Florence, Italy
2Diabetes Agency, University of Florence and Careggi Teaching Hospital, 50141 Florence, Italy
3Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Pieraccini Avenue 18, 50141 Florence, Italy

Received 26 December 2010; Accepted 22 February 2011

Academic Editor: Giovanni Di Pasquale

Copyright © 2011 Matteo Monami et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. The University Group Diabetes Program, “A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. V. Evaluation of pheniformin therapy,” Diabetes, vol. 24, supplement 1, pp. 65–184, 1975. View at Google Scholar
  2. A. D. Rao, N. Kuhadiya, K. Reynolds, and V. A. Fonseca, “Is the combination of sulfonylureas and metformin associated with an increased risk of cardiovascular disease or all- cause mortality? A meta-analysis of observational studies,” Diabetes Care, vol. 31, no. 8, pp. 1672–1678, 2008. View at Publisher · View at Google Scholar
  3. S. Finfer, R. Bellomi, D. Blair et al., “Intensive versus conventional glucose control in critically Ill patients,” The New England Journal of Medicine, vol. 360, no. 13, pp. 1283–1297, 2009. View at Publisher · View at Google Scholar
  4. K. Malmberg, L. Rydén, H. Wedel et al., “FASTTRACK intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity,” European Heart Journal, vol. 26, no. 7, pp. 650–661, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. R. M. Lago, P. P. Singh, and R. W. Nesto, “Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials,” Lancet, vol. 370, no. 9593, pp. 1129–1136, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. S. E. Nissen and K. Wolski, “Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes,” The New England Journal of Medicine, vol. 356, no. 24, pp. 2457–2471, 2007. View at Google Scholar · View at Scopus
  7. S. Singh, Y. K. Loke, and C. D. Furberg, “Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis,” Journal of the American Medical Association, vol. 298, no. 10, pp. 1189–1195, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. “Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” The Lancet, vol. 352, pp. 854–865, 1998.
  9. P. D. Home, S. J. Pocock, H. Beck-Nielsen et al., “Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis,” The New England Journal of Medicine, vol. 357, no. 1, pp. 28–38, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. E. Mannucci, M. Monami, and N. Marchionni, “Rosiglitazone and cardiovascular risk,” The New England Journal of Medicine, vol. 357, no. 9, pp. 938–940, 2007. View at Google Scholar · View at Scopus
  11. E. Mannucci, M. Monami, M. Di Bari et al., “Cardiac safety profile of rosiglitazone: a comprehensive meta-analysis of randomized clinical trials,” International Journal of Cardiology, vol. 143, no. 2, pp. 135–140, 2010. View at Publisher · View at Google Scholar
  12. E. Mannucci and C. M. Rotella, “Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk,” Nutrition, Metabolism and Cardiovascular Diseases, vol. 18, no. 9, pp. 639–645, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. G. G. Sokos, L. A. Nikolaidis, S. Mankad, D. Elahi, and R. P. Shannon, “Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure,” Journal of Cardiac Failure, vol. 12, no. 9, pp. 694–699, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. A. R. Jadad, R. A. Moore, D. Carroll et al., “Assessing the quality of reports of randomized clinical trials: is blinding necessary?” Controlled Clinical Trials, vol. 17, no. 1, pp. 1–12, 1996. View at Publisher · View at Google Scholar · View at Scopus
  15. D. B. Petitti, “Approaches to heterogeneity in meta-analysis,” Statistics in Medicine, vol. 20, no. 23, pp. 3625–3633, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. D. Moher, A. Liberati, J. Tetzlaff et al., “Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement,” Annals of Internal Medicine, vol. 151, no. 4, pp. 264–269, 2009. View at Google Scholar
  17. G. A. Diamond, L. Bax, and S. Kaul, “Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death,” Annals of Internal Medicine, vol. 147, no. 8, pp. 578–581, 2007. View at Google Scholar · View at Scopus
  18. J. J. Shuster, L. S. Jones, and D. A. Salmon, “Fixed vs random effects meta-analysis in rare event studies: the Rosiglitazone link with myocardial infarction and cardiac death,” Statistics in Medicine, vol. 26, no. 24, pp. 4375–4385, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. J. Rosenstock, J. Reusch, M. Bush, F. Yang, and M. Stewart, “Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing,” Diabetes Care, vol. 32, no. 10, pp. 1880–1886, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Gill, B. J. Hoogwerf, J. Burger et al., “Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study,” Cardiovascular Diabetology, vol. 9, article 6, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Kadowaki, M. Namba, A. Yamamura, H. Sowa, A. M. Wolka, and R. G. Brodows, “Exenatide exhibits dose-dependent effects on glycemic control over 12 weeks in Japanese patients with suboptimally controlled type 2 diabetes,” Endocrine Journal, vol. 56, no. 3, pp. 415–424, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. B. Zinman, B. J. Hoogwerf, S. Durán García et al., “The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial,” Annals of Internal Medicine, vol. 146, no. 7, pp. 477–485, 2007. View at Google Scholar · View at Scopus
  23. Y. Gao, K. H. Yoon, L. M. Chuang et al., “Efficacy and safety of exenatide in patients of Asian descent with type 2 diabetes inadequately controlled with metformin or metformin and a sulphonylurea,” Diabetes Research and Clinical Practice, vol. 83, no. 1, pp. 69–76, 2009. View at Publisher · View at Google Scholar · View at Scopus
  24. R. A. DeFronzo, C. Triplitt, Y. Qu, M. S. Lewis, D. Maggs, and L. C. Glass, “Effects of exenatide plus rosiglitazone on β-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin,” Diabetes Care, vol. 33, no. 5, pp. 951–957, 2010. View at Publisher · View at Google Scholar
  25. C. M. Apovian, R. M. Bergenstal, R. M. Cuddihy et al., “Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes,” American Journal of Medicine, vol. 123, no. 5, pp. 468.e9–468.e17, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. T. J. Moretto, D. R. Milton, T. D. Ridge et al., “Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study,” Clinical Therapeutics, vol. 30, no. 8, pp. 1448–1460, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. J. Liutkus, J. Rosas Guzman, P. Norwood et al., “A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin,” Diabetes, Obesity and Metabolism, vol. 12, no. 12, pp. 1058–1065, 2010. View at Publisher · View at Google Scholar
  28. R. A. DeFronzo, R. E. Ratner, J. Han, D. D. Kim, M. S. Fineman, and A. D. Baron, “Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2,” Diabetes Care, vol. 28, no. 5, pp. 1092–1100, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. J. B. Buse, R. R. Henry, J. Han, D. D. Kim, M. S. Fineman, and A. D. Baron, “Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes,” Diabetes Care, vol. 27, no. 11, pp. 2628–2635, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. D. M. Kendall, M. C. Riddle, J. Rosenstock et al., “Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea,” Diabetes Care, vol. 28, no. 5, pp. 1083–1091, 2005. View at Publisher · View at Google Scholar · View at Scopus
  31. G. Derosa, P. Maffioli, S. A. T. Salvadeo et al., “Exenatide versus glibenclamide in patients with diabetes,” Diabetes Technology and Therapeutics, vol. 12, no. 3, pp. 233–240, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. R. Bergenstal, A. Lewin, T. Bailey, D. Chang, T. Gylvin, and V. Roberts, “Efficacy and safety of biphasic insulin aspart 70/30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea,” Current Medical Research and Opinion, vol. 25, no. 1, pp. 65–75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. M. A. Nauck, S. Duran, D. Kim et al., “A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study,” Diabetologia, vol. 50, no. 2, pp. 259–267, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. A. H. Barnett, J. Burger, D. Johns et al., “Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial,” Clinical Therapeutics, vol. 29, no. 11, pp. 2333–2348, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. http://www.clinicaltrials.gov/, 2010.
  36. R. J. Heine, L. F. Van Gaal, D. Johns, M. J. Mihm, M. H. Widel, and R. G. Brodows, “Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial,” Annals of Internal Medicine, vol. 143, no. 8, pp. 559–569, 2005. View at Google Scholar · View at Scopus
  37. M. C. Bunck, M. Diamant, A. Cornér et al., “One-year treatment with exenatide improves β-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial,” Diabetes Care, vol. 32, no. 5, pp. 762–768, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Diamant, L. Van Gaal, S. Stranks et al., “Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial,” The Lancet, vol. 375, no. 9733, pp. 2234–2243, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. S. N. Davis, D. Johns, D. Maggs, H. Xu, J. H. Northrup, and R. G. Brodows, “Exploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combination with oral antidiabetes agents,” Diabetes Care, vol. 30, no. 11, pp. 2767–2772, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. D. Kim, L. MacConell, D. Zhuang et al., “Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes,” Diabetes Care, vol. 30, no. 6, pp. 1487–1493, 2007. View at Publisher · View at Google Scholar · View at Scopus
  41. R. M. Bergenstal, C. Wysham, L. MacConell et al., “Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial,” The Lancet, vol. 376, pp. 431–439, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Madsbad, O. Schmitz, J. Ranstam, G. Jakobsen, and D. R. Matthews, “Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial,” Diabetes Care, vol. 27, no. 6, pp. 1335–1342, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Vilsbøll, “Liraglutide: a once-daily GLP-1 analogue for the treatment of Type 2 diabetes mellitus,” Expert Opinion on Investigational Drugs, vol. 16, no. 2, pp. 231–237, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. Y. Seino, M. F. Rasmussen, M. Zdravkovic, and K. Kaku, “Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: a double-blind, randomized, controlled trial in Japanese patients with type 2 diabetes,” Diabetes Research and Clinical Practice, vol. 81, no. 2, pp. 161–168, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. K. Kaku, M. F. Rasmussen, P. Clauson, and Y. Seino, “Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes,” Diabetes, Obesity and Metabolism, vol. 12, no. 4, pp. 341–347, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. D. Russell-Jones, A. Vaag, O. Schmitz et al., “Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial,” Diabetologia, vol. 52, no. 10, pp. 2046–2055, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. B. Zinman, J. Gerich, J. B. Buse et al., “Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met + TZD),” Diabetes Care, vol. 32, pp. 1224–1230, 2010. View at Google Scholar · View at Scopus
  48. M. Marre, J. Shaw, M. Brändle et al., “Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU),” Diabetic Medicine, vol. 26, no. 3, pp. 268–278, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Nauck, A. Frid, K. Hermansen et al., “Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study,” Diabetes Care, vol. 32, pp. 84–90, 2009. View at Publisher · View at Google Scholar
  50. M. N. Feinglos, M. F. Saad, F. X. Pi-Sunyer, B. An, and O. Santiago, “Effects of liraglutide (NN2211), a long-acting GLP-1 analogue, on glycaemic control and bodyweight in subjects with Type 2 diabetes,” Diabetic Medicine, vol. 22, no. 8, pp. 1016–1023, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Garber, R. Henry, R. Ratner et al., “Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial,” The Lancet, vol. 373, no. 9662, pp. 473–481, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. R. E. Pratley, M. Nauck, T. Bailey et al., “Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial,” Lancet, vol. 375, no. 9724, pp. 1447–1456, 2010. View at Publisher · View at Google Scholar · View at Scopus