GLP-1 Receptor Agonist Albiglutide Demonstrates ‘Harmonious’ Cardiovascular Outcomes in Type 2 Diabetics Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease : The HARMONY OUTCOMES trial

The results of the recently published Harmony-Outcomes study in The Lancet, led by Professor Stefano Del Prato, University of Pisa, Italy and Professor John McMurray, University of Glasgow, UK, have demonstrated that among patients with concomitant type 2 diabetes and cardiovascular disease, albiglutide, a glucagon-like peptide 1 receptor agonist is superior to placebo in the reduction of major adverse cardiovascular events. The study suggests that evidence-based glucagon-like peptide 1 receptor agonists should be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes.

Albiglutide is a GLP-1 receptor agonist that is produced through the genetic fusion of two tandem copies of modified human GLP to human albumin. The final generated protein is long-acting and can be injected weekly. To study the impact of albiglutide on the risk of cardiovascular events in diabetic patients, Hernandez et al conducted a double-blinded, randomized, placebo-controlled, multi-center trial across 28 countries. Patient population (n=9463) comprised of individuals older than 40 years old with type 2 diabetes and cardiovascular disease. They were randomly assigned in the ratio of 1:1 to either of the two groups, receiving a once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo in addition to standard care. The primary endpoint was the first occurrence of cardiovascular death, stroke, or myocardial infarction. Closed testing for superiority was prespecified if non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1.30.

Overall, 9463 participants were followed for a median of 1.6 years. In the study, Hernandez and his colleagues found that the incidence rate of primary composite endpoint was 4.6 events per 100 person-years in the albiglutide group compared to 5.9 events per 100 person-years in placebo group (hazard ratio 0.78, 95% CI 0.68-0.90), indicating superiority of albiglutide over placebo (p<0.0001 for noninferiority, p=0.006 for superiority). Therefore, in patients with type 2 diabetes and cardiovascular disease receiving standard care, the addition of once-weekly albiglutide reduced the risk of the primary composite outcome – death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke – by 22%, compared with the addition of placebo. Overall, the number of patients who would need to be treated with albiglutide to prevent one event over a median of 1.6 years was 50. It was also noted that the incidence of acute pancreatitis (10 patients in the albiglutide group and 7 patients in the placebo group), pancreatic cancer (6 patients in the albiglutide group and 5 patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. Additionally, the data indicated that there were 3 (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group.

Emphasizing on the importance of their study, authors Dr. Stefano Del Prato and Dr. McMurray expressed their enthusiasm, “We are very excited by these results which add to the evidence that certain GLP-1-receptor agonists reduce cardiovascular events in patients with type 2 diabetes. This new therapeutic approach offers physicians a further means of reducing the most common and deadly complication faced by our patients with type 2 diabetes. These are impressive findings, with a reduction in risk at least as large as that obtained with traditional cardiovascular drugs and clearly an important addition to the therapeutic approaches available to tackle this problem.”