drugset / Trial / NCT01179048
Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results
RandomizedParallel-groupDouble-blindTreatment
Summary
This trial is conducted in Africa, Asia, Europe, and North and South America. The aim of this trial is to determine the long term effect of liraglutide on cardiovascular events in subjects with type 2 diabetes.
Timeline
- Start
- 2010-08-31
- Primary completion
- 2015-12-17
- Completion
- 2015-12-17
Outcome
Met primary endpoint
registry Liraglutide vs Placebo; p = 0.005; Hazard Ratio (HR) 0.868 (95% CI 0.778 to 0.968) NCT01179048 ↗
paper The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) PMID 27295427 ↗
release “LEADER trial, comprising more than 9,300 people with an average treatment of approximately four years, significantly reduced the risk of major adverse cardiovascular events.” novonordisk.com ↗
release “met the primary endpoint of showing non-inferiority as well as demonstrating superiority” novonordisk.com ↗
release “In the LEADER trial, Victoza® statistically significantly reduced the risk of cardiovascular death, non-fatal myocardial infarction (heart attack) and non-fatal stroke by 13% versus placebo” novonordisk.com ↗
Publications
- Background Verma S, Bain SC, Monk Fries T, Mazer CD, Nauck MA, Pratley RE, Rasmussen S, Saevereid HA, Zinman B, Buse JB. Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials. Diabetes Obes Metab. 2019 Jul;21(7):1745-1751. doi: 10.1111/dom.13698. Epub 2019 Apr 2.
- Background Hinton W, Feher M, Munro N, Walker M, de Lusignan S. Real-world prevalence of the inclusion criteria for the LEADER trial: Data from a national general practice network. Diabetes Obes Metab. 2019 Jul;21(7):1661-1667. doi: 10.1111/dom.13710. Epub 2019 Apr 11.
- Results Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13.
- Results Petrie JR, Marso SP, Bain SC, Franek E, Jacob S, Masmiquel L, Leiter LA, Haluzik M, Satman I, Omar M, Shestakova M, Van Gaal L, Mann JF, Baeres FM, Zinman B, Poulter NR; LEADER investigators. LEADER-4: blood pressure control in patients with type 2 diabetes and high cardiovascular risk: baseline data from the LEADER randomized trial. J Hypertens. 2016 Jun;34(6):1140-50. doi: 10.1097/HJH.0000000000000890.
- Results Masmiquel L, Leiter LA, Vidal J, Bain S, Petrie J, Franek E, Raz I, Comlekci A, Jacob S, van Gaal L, Baeres FM, Marso SP, Eriksson M; LEADER investigators. LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial. Cardiovasc Diabetol. 2016 Feb 10;15:29. doi: 10.1186/s12933-016-0341-5.
- Results Satman I, R Rea R, Eriksson M, Mosenzon O, Pratley R, M Baeres F, D Orsted D, F Mann J; LEADER Trial Investigators. LEADER-6: Baseline renal function and associated factors in a high cardiovascular risk type 2 diabetes population. J Diabetes Complications. 2016 Nov-Dec;30(8):1631-1639. doi: 10.1016/j.jdiacomp.2016.06.001. Epub 2016 Jun 3.
- Results Rutten GE, Tack CJ, Pieber TR, Comlekci A, Orsted DD, Baeres FM, Marso SP, Buse JB; LEADER Investigators. LEADER 7: cardiovascular risk profiles of US and European participants in the LEADER diabetes trial differ. Diabetol Metab Syndr. 2016 Jun 2;8:37. doi: 10.1186/s13098-016-0153-5. eCollection 2016.
- Results Marso SP, Poulter NR, Nissen SE, Nauck MA, Zinman B, Daniels GH, Pocock S, Steinberg WM, Bergenstal RM, Mann JF, Ravn LS, Frandsen KB, Moses AC, Buse JB. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. Am Heart J. 2013 Nov;166(5):823-30.e5. doi: 10.1016/j.ahj.2013.07.012. Epub 2013 Oct 2.
- Results Steinberg WM, Nauck MA, Zinman B, Daniels GH, Bergenstal RM, Mann JF, Steen Ravn L, Moses AC, Stockner M, Baeres FM, Marso SP, Buse JB; LEADER Trial investigators. LEADER 3--lipase and amylase activity in subjects with type 2 diabetes: baseline data from over 9000 subjects in the LEADER Trial. Pancreas. 2014 Nov;43(8):1223-31. doi: 10.1097/MPA.0000000000000229.
- Results Daniels GH, Hegedus L, Marso SP, Nauck MA, Zinman B, Bergenstal RM, Mann JF, Derving Karsbol J, Moses AC, Buse JB, Tuttle RM; LEADER Trial Investigators. LEADER 2: baseline calcitonin in 9340 people with type 2 diabetes enrolled in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial: preliminary observations. Diabetes Obes Metab. 2015 May;17(5):477-86. doi: 10.1111/dom.12444. Epub 2015 Feb 23.
- Results Steinberg WM, Buse JB, Ghorbani MLM, Orsted DD, Nauck MA; LEADER Steering Committee; LEADER Trial Investigators. Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial. Diabetes Care. 2017 Jul;40(7):966-972. doi: 10.2337/dc16-2747. Epub 2017 May 5.
- Results Mann JFE, Orsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornoe K, Zinman B, Buse JB; LEADER Steering Committee and Investigators. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med. 2017 Aug 31;377(9):839-848. doi: 10.1056/NEJMoa1616011.
- Results Hegedus L, Sherman SI, Tuttle RM, von Scholten BJ, Rasmussen S, Karsbol JD, Daniels GH; LEADER Publication Committee on behalf of the LEADER Trial Investigators. No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial. Diabetes Care. 2018 Mar;41(3):620-622. doi: 10.2337/dc17-1956. Epub 2017 Dec 26.
- Results Marso SP, Nauck MA, Monk Fries T, Rasmussen S, Treppendahl MB, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Myocardial Infarction Subtypes in Patients With Type 2 Diabetes Mellitus and the Effect of Liraglutide Therapy (from the LEADER Trial). Am J Cardiol. 2018 Jun 15;121(12):1467-1470. doi: 10.1016/j.amjcard.2018.02.030. Epub 2018 Mar 15.
- Results Verma S, Bhatt DL, Bain SC, Buse JB, Mann JFE, Marso SP, Nauck MA, Poulter NR, Pratley RE, Zinman B, Michelsen MM, Monk Fries T, Rasmussen S, Leiter LA; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Effect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular Disease: Results of the LEADER Trial. Circulation. 2018 May 15;137(20):2179-2183. doi: 10.1161/CIRCULATIONAHA.118.033898. No abstract available.
- Results Nauck MA, Jensen TJ, Rosenkilde C, Calanna S, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Neoplasms Reported With Liraglutide or Placebo in People With Type 2 Diabetes: Results From the LEADER Randomized Trial. Diabetes Care. 2018 Aug;41(8):1663-1671. doi: 10.2337/dc17-1825. Epub 2018 Jun 13.
- Results Zinman B, Marso SP, Christiansen E, Calanna S, Rasmussen S, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Hypoglycemia, Cardiovascular Outcomes, and Death: The LEADER Experience. Diabetes Care. 2018 Aug;41(8):1783-1791. doi: 10.2337/dc17-2677. Epub 2018 Jun 14.
- Results Nauck MA, Tornoe K, Rasmussen S, Treppendahl MB, Marso SP; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Cardiovascular outcomes in patients who experienced a myocardial infarction while treated with liraglutide versus placebo in the LEADER trial. Diab Vasc Dis Res. 2018 Sep;15(5):465-468. doi: 10.1177/1479164118783935. Epub 2018 Jun 27.
- Results Dhatariya K, Bain SC, Buse JB, Simpson R, Tarnow L, Kaltoft MS, Stellfeld M, Tornoe K, Pratley RE; LEADER Publication Committee on behalf of the LEADER Trial Investigators. The Impact of Liraglutide on Diabetes-Related Foot Ulceration and Associated Complications in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events: Results From the LEADER Trial. Diabetes Care. 2018 Oct;41(10):2229-2235. doi: 10.2337/dc18-1094. Epub 2018 Aug 2.
- Results Verma S, Leiter LA, Mazer CD, Bain SC, Buse J, Marso S, Nauck M, Zinman B, Bosch-Traberg H, Rasmussen S, Michelsen MM, Bhatt DL. Liraglutide Reduces Cardiovascular Events and Mortality in Type 2 Diabetes Mellitus Independently of Baseline Low-Density Lipoprotein Cholesterol Levels and Statin Use. Circulation. 2018 Oct 9;138(15):1605-1607. doi: 10.1161/CIRCULATIONAHA.118.036862. No abstract available.
- Results Mann JFE, Fonseca V, Mosenzon O, Raz I, Goldman B, Idorn T, von Scholten BJ, Poulter NR. Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease. Circulation. 2018 Dec 18;138(25):2908-2918. doi: 10.1161/CIRCULATIONAHA.118.036418.
- Results Verma S, Poulter NR, Bhatt DL, Bain SC, Buse JB, Leiter LA, Nauck MA, Pratley RE, Zinman B, Orsted DD, Monk Fries T, Rasmussen S, Marso SP. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus With or Without History of Myocardial Infarction or Stroke. Circulation. 2018 Dec 18;138(25):2884-2894. doi: 10.1161/CIRCULATIONAHA.118.034516.
- Results Nauck MA, Buse JB, Mann JFE, Pocock S, Bosch-Traberg H, Frimer-Larsen H, Ye Q, Gray A; LEADER Publication Committee for the LEADER Trial Investigators. Health-related quality of life in people with type 2 diabetes participating in the LEADER trial. Diabetes Obes Metab. 2019 Mar;21(3):525-532. doi: 10.1111/dom.13547. Epub 2018 Oct 25.
- Results Zinman B, Nauck MA, Bosch-Traberg H, Frimer-Larsen H, Orsted DD, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Liraglutide and Glycaemic Outcomes in the LEADER Trial. Diabetes Ther. 2018 Dec;9(6):2383-2392. doi: 10.1007/s13300-018-0524-z. Epub 2018 Nov 3.
- Results Gilbert MP, Bain SC, Franek E, Jodar-Gimeno E, Nauck MA, Pratley R, Rea RR, Kerr Saraiva JF, Rasmussen S, Tornoe K, von Scholten BJ, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Effect of Liraglutide on Cardiovascular Outcomes in Elderly Patients: A Post Hoc Analysis of a Randomized Controlled Trial. Ann Intern Med. 2019 Mar 19;170(6):423-426. doi: 10.7326/M18-1569. Epub 2018 Dec 4. No abstract available.
- Heerspink HJL, Collier WH, Chaudhari J, Miao S, Tighiouart H, Appel GB, Caravaca-Fontan F, Floege J, Hannedouche T, Imai E, Jafar TH, Lewis JB, Li PKT, Locatelli F, Maes BD, Neuen BL, Perkovic V, Perrone RD, Remuzzi G, Schena FP, Wanner C, Greene T, Inker LA. A meta-analysis of albuminuria as a surrogate endpoint for kidney failure. Nat Med. 2026 Jan;32(1):281-287. doi: 10.1038/s41591-025-04057-z. Epub 2025 Nov 6.
- Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
- Verma S, Al-Omran M, Leiter LA, Mazer CD, Rasmussen S, Saevereid HA, Sejersten Ripa M, Bonaca MP. Cardiovascular efficacy of liraglutide and semaglutide in individuals with diabetes and peripheral artery disease. Diabetes Obes Metab. 2022 Jul;24(7):1288-1299. doi: 10.1111/dom.14700. Epub 2022 Apr 11.
- Heller SR, Geybels MS, Iqbal A, Liu L, Wagner L, Chow E. A higher non-severe hypoglycaemia rate is associated with an increased risk of subsequent severe hypoglycaemia and major adverse cardiovascular events in individuals with type 2 diabetes in the LEADER study. Diabetologia. 2022 Jan;65(1):55-64. doi: 10.1007/s00125-021-05556-7. Epub 2021 Oct 26.
- Persson F, Bain SC, Mosenzon O, Heerspink HJL, Mann JFE, Pratley R, Raz I, Idorn T, Rasmussen S, von Scholten BJ, Rossing P; LEADER Trial Investigators. Changes in Albuminuria Predict Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Post Hoc Analysis of the LEADER Trial. Diabetes Care. 2021 Apr;44(4):1020-1026. doi: 10.2337/dc20-1622. Epub 2021 Jan 27.
- Verma S, McGuire DK, Bain SC, Bhatt DL, Leiter LA, Mazer CD, Monk Fries T, Pratley RE, Rasmussen S, Vrazic H, Zinman B, Buse JB. Effects of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials. Diabetes Obes Metab. 2020 Dec;22(12):2487-2492. doi: 10.1111/dom.14160. Epub 2020 Sep 4.
- Crowley MJ, McGuire DK, Alexopoulos AS, Jensen TJ, Rasmussen S, Saevereid HA, Verma S, Buse JB. Effects of Liraglutide on Cardiovascular Outcomes in Type 2 Diabetes Patients With and Without Baseline Metformin Use: Post Hoc Analyses of the LEADER Trial. Diabetes Care. 2020 Sep;43(9):e108-e110. doi: 10.2337/dc20-0437. Epub 2020 Jul 9. No abstract available.
- Verma S, Bain SC, Honore JB, F E Mann J, A Nauck M, E Pratley R, Rasmussen S, Sejersten Ripa M, Zinman B, Buse JB. Impact of microvascular disease on cardiovascular outcomes in type 2 diabetes: Results from the LEADER and SUSTAIN 6 clinical trials. Diabetes Obes Metab. 2020 Nov;22(11):2193-2198. doi: 10.1111/dom.14140. Epub 2020 Aug 12.
- Leiter LA, Bain SC, Bhatt DL, Buse JB, Mazer CD, Pratley RE, Rasmussen S, Ripa MS, Vrazic H, Verma S. The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials. Diabetes Obes Metab. 2020 Sep;22(9):1690-1695. doi: 10.1111/dom.14079. Epub 2020 Jun 3.
- Buse JB, Bain SC, Mann JFE, Nauck MA, Nissen SE, Pocock S, Poulter NR, Pratley RE, Linder M, Monk Fries T, Orsted DD, Zinman B; LEADER Trial Investigators. Cardiovascular Risk Reduction With Liraglutide: An Exploratory Mediation Analysis of the LEADER Trial. Diabetes Care. 2020 Jul;43(7):1546-1552. doi: 10.2337/dc19-2251. Epub 2020 May 4.
- Marso SP, Baeres FMM, Bain SC, Goldman B, Husain M, Nauck MA, Poulter NR, Pratley RE, Thomsen AB, Buse JB; LEADER Trial Investigators. Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure. J Am Coll Cardiol. 2020 Mar 17;75(10):1128-1141. doi: 10.1016/j.jacc.2019.12.063.
- Mann JFE, Fonseca VA, Poulter NR, Raz I, Idorn T, Rasmussen S, von Scholten BJ, Mosenzon O; LEADER Trial Investigators. Safety of Liraglutide in Type 2 Diabetes and Chronic Kidney Disease. Clin J Am Soc Nephrol. 2020 Apr 7;15(4):465-473. doi: 10.2215/CJN.11881019. Epub 2020 Mar 4.
- Nauck MA, Kreiner E, Rasmussen S, Saevereid HA, Buse JB; LEADER Trial Investigators. Response to Comment on Nauck et al. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial. Diabetes Care 2019;42:1912-1920. Diabetes Care. 2020 Feb;43(2):e30-e31. doi: 10.2337/dci19-0067. No abstract available.
- Verma S, Bain SC, Buse JB, Idorn T, Rasmussen S, Orsted DD, Nauck MA. Occurence of First and Recurrent Major Adverse Cardiovascular Events With Liraglutide Treatment Among Patients With Type 2 Diabetes and High Risk of Cardiovascular Events: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2019 Dec 1;4(12):1214-1220. doi: 10.1001/jamacardio.2019.3080.
- Nauck MA, Muus Ghorbani ML, Kreiner E, Saevereid HA, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial. Diabetes Care. 2019 Oct;42(10):1912-1920. doi: 10.2337/dc19-0415. Epub 2019 Aug 9.
- Tack CJ, Jacob S, Desouza C, Bain SC, Buse JB, Nauck MA, Petrie JR, Poulter NR, Pratley RE, Stegmann HVBK, Bosch-Traberg H, Startseva E, Zinman B; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Long-term efficacy and safety of combined insulin and glucagon-like peptide-1 therapy: Evidence from the LEADER trial. Diabetes Obes Metab. 2019 Nov;21(11):2450-2458. doi: 10.1111/dom.13826. Epub 2019 Jul 7.
- Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials enrollment criteria to the US type 2 diabetes population. Am J Manag Care. 2018 Apr;24(8 Suppl):S146-S155.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Liraglutide | Peptide | 1.8 mg | Subcutaneous |