Primary outcome
What LEADER measured first
| Liraglutiden=4,668 | Placebon=4,672 |
|---|---|
| 13.0 | 14.9 |
Phase 3 · Liraglutide
LEADER trial results
A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular Events
Time From Randomisation to First Occurrence of Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke (a Composite Cardiovascular Outcome) (percentage of subjects), from randomisation (visit 3; month 0) to last contact (visit 16; up to month 60+30 days). Liraglutide: 13.0; Placebo: 14.9.
- Participants
- 9,341
- Status
- completed
- Completed
- 2015-12-17
- Sponsor
- Novo Nordisk A/S
As posted on ClinicalTrials.gov (NCT01179048), updated at source Jul 17, 2019. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.
Side effects by arm
Side effects in LEADER
Percent of participants affected, Adverse events from randomisation (visit 3; month 0) and until follow up (visit 16; up to month 60+30 days of post-treatment follow-up).. The most common events the registry lists.
| Event | Liraglutide | Placebo |
|---|---|---|
| Any serious event | 49.7% | 50.4% |
| Nausea | 11.1% | 2.8% |
| Diarrhoea | 5.7% | 2.2% |
Secondary outcomes
What else it measured
| Liraglutiden=4,668 | Placebon=4,672 |
|---|---|
| 20.3 | 22.7 |
| Liraglutiden=4,668 | Placebon=4,672 |
|---|---|
| 8.2 | 9.6 |
| Measure | Liraglutiden=4,668 | Placebon=4,672 |
|---|---|---|
| Cardiovascular death | 4.7 | 6.0 |
| Non-fatal stroke | 3.4 | 3.8 |
| Non-fatal myocardial infarction | 6.0 | 6.8 |
| Unstable angina pectoris (hospitalisation) | 2.6 | 2.7 |
| Coronary revascularisation | 8.7 | 9.4 |
| Heart failure (hospitalisation) | 4.7 | 5.3 |
| Liraglutiden=4,668 | Placebon=4,672 |
|---|---|
| 7.6 | 8.9 |
| Measure | Liraglutiden=4,668 | Placebon=4,672 |
|---|---|---|
| Nephropathy composite | 5.7 | 7.2 |
| New onset of persistent macroalbuminuria | 3.4 | 4.6 |
| Persistent doubling of serum creatinine | 1.9 | 2.1 |
| Need for continuous renal-replacement therapy | 1.2 | 1.4 |
| Death due to renal disease | 0.2 | 0.1 |
| Retinopathy composite | 2.3 | 2.0 |
| Treatment with photocoagulation/intravitreal agent | 2.1 | 1.8 |
| Development of diabetes-related blindness | 0.0 | 0.02 |
| Vitreous haemorrhage | 0.7 | 0.5 |
The trial
How LEADER was run
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.
- Liraglutide
- Placebo
Who could join the trial
Inclusion Criteria: - Type 2 diabetes - Age min. 50 years at screening and concomitant cardiovascular, cerebrovascular or peripheral vascular disease or chronic renal failure or chronic heart failure OR age min. 60 years at screening and other specified risk factors of cardiovascular disease - HbA1c: 7.0% or above - Anti-diabetic drug naive or treated with one or more oral anti-diabetic drugs (OADs) or treated with human NPH insulin or long-acting insulin analogue or premixed insulin, alone or in combination with OAD(s) Exclusion Criteria: - Type 1 diabetes - Use of a glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide or other) or pramlintide or any dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 months prior to screening (trial start) - Use of insulin other than human NPH insulin or long-acting insulin analogue or premixed insulin within 3 months prior to screening. Short-term use of other insulin during this period in connection with intercurrent illness is allowed, at Investigator's discretion
Published papers
Papers from LEADER
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.
GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.