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

By Matteo Monami, Francesco Cremasco, Caterina Lamanna, Claudia Colombi, Carla Maria Desideri, Iacopo Iacomelli, Niccolò Marchionni and Edoardo Mannucci

Abstract

Objective. Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists. Design and Methods. MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration ≥12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events. Results. Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50–1.08), P = .12 (0.85 (0.50–1.45), P = .55, and 0.69 (0.40–1.22), P = .20, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25–0.83), P = .009, and 1.05 (0.63–1.76), P = .84, respectively. Conclusions. To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3092497
Provided by: PubMed Central

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Citations

  1. (2007). 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,”
  2. (2010). A placebocontrolled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin,” Diabetes,
  3. (2001). Approaches to heterogeneity in meta-analysis,”
  4. (1996). Assessing the quality of reports of randomized clinical trials: is blinding necessary?”
  5. (2004). B u s e ,R .R .H e n r y
  6. (2009). Br¨ andle et al., “Liraglutide, a oncedaily 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
  7. (2010). Cardiac safety profile of rosiglitazone: a comprehensive meta-analysis of randomizedclinicaltrials,”InternationalJournalofCardiology,
  8. (2007). Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials,”
  9. (2010). D e F r o n z o ,C .T r i p l i t t
  10. (2008). Dose-dependent improvement in glycemia with once-daily liraglutide without hypoglycemia or weight gain: a doubleblind, randomized, controlled trial
  11. (2007). Dur´ an Garc´ ıa et al., “The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial,”
  12. Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study,”
  13. (1998). Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2
  14. (2005). Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformintreated patients with type 2,”
  15. (2005). 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,
  16. (2005). Effects of liraglutide (NN2211), a long-acting GLP1 analogue, on glycaemic control and bodyweight
  17. (2007). Effects of onceweekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes,” Diabetes Care,
  18. (2009). Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin,
  19. (2009). 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,”
  20. (2009). Efficacy and safety of exenatide in patients of Asian descent with type 2 diabetes inadequately controlled with metformin or metformin and a
  21. (2010). 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,”
  22. (2010). Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione
  23. (2008). 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,”
  24. (2009). Exenatide exhibits dose-dependent effects on glycemic control over 12 weeks in Japanese patients with suboptimally controlled type 2 diabetes,”
  25. (2005). Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial,”
  26. (2007). Exploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combinationwithoralantidiabetesagents,”
  27. (2007). Fixed vs random effects meta-analysis in rare event studies: the Rosiglitazone link with myocardial infarction and cardiac death,”
  28. (2008). Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk,”
  29. (2010). G.Derosa,P.Maffioli,S.A.T .Salvadeoetal.,“Ex enatideversus glibenclamide in patients with diabetes,”
  30. (2006). Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure,”
  31. (1975). Group Diabetes Program, “A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes.
  32. (2010). Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagonlike peptide-1 analogue liraglutide as add-on to sulphonylurea
  33. (2004). 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,
  34. (2009). Intensive versus conventionalglucosecontrolincriticallyIllpatients,”TheNew England
  35. (2005). K.Malmberg,L.Ryd´ en,H.Wedel et al.,“FASTTRACKintense metaboliccontrolbymeansofinsulininpatientswithdiabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity,”
  36. (2009). Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial,”
  37. (2010). 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,”
  38. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD5 met+SU): a randomised controlled trial,”
  39. (2007). Liraglutide: a once-daily GLP-1 analogue for the treatment of Type 2 diabetes mellitus,”
  40. (2007). Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis,”
  41. (2007). N i s s e na n dK .W o l s k i ,“ E ffect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes,” The New England
  42. (2010). Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial,”
  43. (2009). 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,
  44. (2009). Potentialofalbiglutide,along-actingGLP-1receptoragonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing,” Diabetes Care,
  45. (2009). Preferred reporting items for systematic reviews and meta-analyses:
  46. (2010). R.M.Cuddihyet al.,“Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes,”
  47. (2007). Rosiglitazone evaluated for cardiovascular outcomes—an interim analysis,”
  48. (2007). 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,”
  49. (2007). Uncertain effects of rosiglitazone on the risk for myocardial infarction and cardiovascular death,”