1. Patients with type 2 diabetes who received liraglutide were observed to have a significantly lower incidence of the composite of death from cardiovascular causes, nonfatal MI, and nonfatal stroke, versus patients who received placebo.
2. The rates of both all-cause mortality and nephropathy were significantly lower for patients who received liraglutide than for patients who received placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Liraglutide is a glucagon-like peptide 1 (GLP-1) analogue, approved for the treatment of type 2 diabetes mellitus (T2DM). While the microvascular benefits of this drug are well characterized through its effect on improving glycemic control, its macrovascular effects are less than certain at this point.
In this multicenter, double-blind, placebo-controlled trial, patients were randomized in a 1:1 ratio to receive a once daily liraglutide or placebo subcutaneous injection. The primary outcome in the study was the first occurrence of death from cardiovascular causes, nonfatal MI, or nonfatal stroke. The primary outcome was found to be significantly lower in the liraglutide group than in the placebo group. Additionally, death from CV causes alone was also found to be significantly lower in the liraglutide group than in the placebo group. All-cause mortality was also found to be significantly lower in the liraglutide group than in the placebo group, as well.
This study draws strength from strict inclusion and exclusion criteria that made patients, effectively, treatment naïve at baseline: T2DM patients with HbA1c >7.0% who had not received any medication for this condition previously. Its impact, however, is somewhat limited by the modest follow-up period of 42-60 months.
Click to read the study, published today in NEJM
Relevant Reading: Cardiovascular outcome trials of glucose-lowering drugs or strategies in type 2 diabetes
In-Depth [randomized controlled trial]: This study was a multicenter, double-blind, placebo-controlled trial, that included a total of 9340 patients. The patients were randomized in a 1:1 ratio to receive a once daily liraglutide or placebo subcutaneous injection. The mean follow-up was 3.8 years. The primary composite outcome (first occurrence of death from cardiovascular causes, nonfatal MI, or nonfatal stroke) occurred in fewer patients in the liraglutide group 13.0% than in the placebo group 14.9% (HR 0.87; 95%CI 0.78 to 0.97; p < 0.001 for non-inferiority; p = 0.01 for superiority). Death from CV causes was significantly lower in the liraglutide group 4.7% than in the placebo group 6.0% (HR 0.78; 95%CI 0.66 to 0.93; p = 0.007). The rate of all-cause mortality was also significantly lower in the liraglutide group 8.2% than in the placebo group 9.6% (HR 0.85; 95%CI 0.74 to 0.97; p = 0.02). The rate of nephropathy was significantly lower in the liraglutide group than in the placebo group (1.5 vs 1.9 events per hundred patient-years; HR 0.78; 95%CI 0.67 to 0.92; p = 0.003).
Image: PD
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