Once weekly injectable albiglutide reduces major cardiovascular events in type II diabetics with known cardiovascular disease
EBM Focus - Volume 13, Issue 36
Treatment goals for patients with type II diabetes traditionally focus on reducing hemoglobin A1C (HbA1C). With the advent of a number of new options however, clinicians can now select agents shown to improve patient-oriented outcomes rather than just HbA1C. Several trials have examined cardiovascular outcomes in glucagon-like peptide (GLP) 1 agonists. The LEADER trial showed that liraglutide could reduce myocardial infarctions and all-cause mortality in patients with type 2 diabetes who had increased cardiovascular risk and the SUSTAIN-6 trial demonstrated lower rates of nonfatal myocardial infarction and stroke in similar patients treated with semaglutide. Now, a recent multicenter study examined albiglutide in a randomized placebo-controlled trial with over 9,000 patients with type II diabetes. Patients had a mean HbA1C of 8.7% and 70% had known cardiovascular disease. Over 75% in each group were taking a biguanide and were on therapy for cardiovascular disease including an aspirin and statin. The primary composite outcome was major cardiovascular events which consisted of myocardial infarction, stroke, and cardiovascular death. The investigators powered the trial for noninferiority, with plans for superiority analysis if the noninferiority margin was met.
Over an average of 18 months of follow up, there were fewer major cardiovascular events in the albiglutide group than the placebo group, which met the noninferiority margin allowing for superiority analysis for the primary outcome (4.6 events per 100 person-years in albiglutide group vs. 5.9 events per 100 person-years in placebo group, hazard ratio 0.78, NNT = 50 over 1.6 years). This was primarily driven by a a single component of the composite outcome, nonfatal and fatal MI. There was no difference in the secondary outcome of death from any cause or cardiovascular death. Patients in the albiglutide group had greater weight loss (1.5 pounds) and a lower likelihood of beginning insulin therapy. In each group, approximately one quarter of participants discontinued the weekly injections, although only 2% had injection site reactions. Hypoglycemia rates were lower in the placebo group than the albiglutide group.
This trial demonstrates albiglutide is safe for patients with type II diabetes and cardiovascular disease. It is worth noting the drug has been withdrawn from the US market, although this was not for safety reasons. Also GLP-1 agonists have black box warnings regarding concerns about thyroid cancer risk. Albiglutide is available in other countries and this trial may serve as an impetus for its reintroduction in the US, particularly if follow-up results show a survival advantage with albiglutide. This trial did not find a survival benefit but a duration of only 18 months is likely too short to reliably determine if a difference in survival exists or not.
Focus Point: Albiglutide may reduce the risk of myocardial infarction in patients with type II diabetes and known cardiovascular disease.
DynaMed Plus EBM Focus Editorial Team
This EBM Focus was written by Carina Brown, MD, Faculty Development and Information Mastery Fellow and Clinical Instructor at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed Plus and Associate Professor in Family Medicine at the University of Massachusetts Medical School and Katharine DeGeorge, MD, MS, Assistant Professor in Family Medicine at the University of Virginia and Clinical Editor at DynaMed Plus.