Arber Nuhaj, M.D.
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
NEJM, 2016; 375: 311-322
The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) was initiated in 2010 to assess the long term effects on cardiovascular outcomes of Liraglutide. The study was a multicenter, double blind, randomized controlled trial at 410 sites and 32 countries. 9340 subjects were included and the minimum planned follow-up was 42 months, with a maximum of 60 months of receiving the assigned regimen, and an additional 30 days of follow-up afterward.
After careful review of the study, our assessment is:
- Liraglutide (Victoza) was shown to reduce cardiovascular outcomes in patients with cardiovascular disease between 50 – 60 years old, but did not improve cardiovascular outcomes for patients > 60 years old. Liraglutide may be beneficial for a very small group of patients with significant cardiovascular disease.
- Death from cardiovascular causes occurred in fewer patients in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]). The study reports that there were 219 deaths from cardiovascular causes in the Liraglutide group (17 fatal Myocardial Infarction and 16 fatal Strokes) while in the placebo group there were 278 deaths from cardiovascular causes (28 fatal Myocardial Infarctions and 25 fatal strokes). Considering that Myocardial Infarction and Strokes are usually significant causes of death among patients with cardiovascular disease. The exact cardiovascular causes of death of the study patients were not clearly stated in the article. For example, in the Liraglutide group, 219 patients died from cardiovascular causes yet only 33 have been reported to have died from MI or Stroke. This makes it difficult to assess the benefit of Liraglutide as a medication that could improve cardiovascular outcomes.
- The 36 month analysis of HA1C showed a mean difference between the liraglutide group and the placebo group of −0.40 percentage points (95% CI −0.45 to −0.34), a negligible effect in glycemic control. Considering the modest glycemic control, the cost of the medication, and the questionable C-V benefit in a small group of European subjects, we feel that the medication is not a first choice for glycemic control.
- BIAS ALERT: The study was supported by Novo Nordisk.