Hernandez AF, et al. - Researchers performed a double-blind, randomized, placebo-controlled trial to determine the effectiveness and safety of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Results of this study suggested that albiglutide was superior to placebo for major adverse cardiovascular events in patients with type 2 diabetes and cardiovascular disease. As part of a comprehensive strategy to reduce the risk of cardiovascular events in type 2 diabetic patients, evidence-based glucagon-like peptide 1 receptor agonists should be considered.

Methods

• This trial was conducted in 610 sites across 28 countries.
• Patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) were randomly assigned to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care.
• An interactive voice or web response system were used by investigators to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation.
• The primary outcome was the first occurrence of cardiovascular death, myocardial infarction, or stroke, and was evaluated in the intention-to-treat population.
• 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.

Results

• Between July 1, 2015 and November 24, 2016, patients were screened.
• In this analysis, 10,793 subjects were screened, and 9,463 participants were enlisted and randomly assigned to receive albiglutide (n=4,731) or placebo (n=4,732).
• On November 8, 2017, 611 primary endpoints and a median follow-up of at least 1.5 years had accrued, and study participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018.
• Findings revealed that the primary composite outcome occurred in 338 (7%) of 4,731 subjects at an incidence rate of 4.6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4,732 patients at an incidence rate of 5.9 events per 100 person-years in the placebo group (hazard ratio 0.78, 95% CI 0.68–0.90), which showed that albiglutide was superior to placebo (p < 0.0001 for non-inferiority; p=0.0006 for superiority).
• It was 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.
• The present 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.