Practice pearl: liraglutide and cardiovascular and renal events in type 2 diabetes

Review of: Marso S, Daniels G, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322. Mann J, Orsted D, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2 Diabetes. N Engl J Med 2017; 377: 839-848. This comprehensive research project, LEADER, led to two reports, one focusing on the effect of liraglutide on cardiovascular events, and the second one reporting on the renal effects on the same study population. The study group included 9340 patients with type 2 diabetes. Patients were required to have type 2 diabetes and an age 50 with a previous cardiovascular problem or chronic heart failure, or an age of 60 with at least one cardiovascular risk factor. Patients were randomized to 1.8 mg (or the maximum tolerated dose) of liraglutide, or placebo. The median follow up was 3.8 years. The primary cardiovascular outcome, a combined endpoint of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, was seen in 13% (608 of 4668 patients) treated with liraglutide versus 14.9 % (694 of 4672 patients) in the placebo patients (HR 0.87; 95% confidence interval [CI] 0.78 to 0.97; P = 0.01 for superiority). Death from cardiovascular disease and death from any cause were also lower in the liraglutide group. The rates for nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were not significantly reduced. In the renal report, the renal outcome was reduced in the liraglutide versus the placebo group (268 of 4668 versus 337 out of 4672 in the placebo group; HR 0.78; CI 0.67 to 0.92; p = 0.003). This improvement was mainly driven by a lower rate of the new onset of persistent macroalbuminuria in the liraglutide patients (161 vs 215 patients; HR 0.74; 95% CI, 0.60 to 0.91; p = 0.004), while the rates of other renal adverse events were similar in both groups. When taken together these two reports are the first data to show that the glucagon-like peptide 1 (GLP-1) analogue liraglutide can reduce cardiovascular events and halt progression to macroalbuminuria in patients with Type 2 diabetes.