In a landmark trial of 9,463 patients, the GLP-1 receptor agonist albiglutide reduced major cardiovascular events by 22% compared to placebo in people with type 2 diabetes and existing heart disease.
22% reduction in cardiovascular eventsHazard ratio of 0.78 for the composite of cardiovascular death, heart attack, or stroke in 9,463 patients over 1.6 years
What the researchers found
The primary composite outcome of cardiovascular death, myocardial infarction, or stroke occurred in 338 patients (7%) in the albiglutide group at a rate of 4.6 events per 100 person-years, compared to 428 patients (9%) in the placebo group at 5.9 events per 100 person-years. This yielded a hazard ratio of 0.78 (95% CI: 0.68–0.90), demonstrating superiority of albiglutide over placebo (p=0.0006 for superiority, p<0.0001 for non-inferiority).
Safety outcomes were reassuring: acute pancreatitis occurred in 10 albiglutide vs. 7 placebo patients, pancreatic cancer in 6 vs. 5 patients, and medullary thyroid carcinoma in zero patients in both groups. Treatment-related deaths were rare (2 in albiglutide, 3 in placebo).
Why it matters
Harmony Outcomes was one of the pivotal cardiovascular outcomes trials that established GLP-1 receptor agonists as not just diabetes medications but cardiovascular protective agents. This trial specifically showed that the cardiovascular benefits extend to albiglutide, broadening the evidence base for the entire GLP-1 class. These results contributed to major guideline changes recommending GLP-1 agonists for diabetic patients with cardiovascular disease, regardless of blood sugar control.
How the study worked
This was a double-blind, randomized, placebo-controlled trial (Harmony Outcomes) conducted across 610 sites in 28 countries. Patients aged 40 and older with type 2 diabetes and established cardiovascular disease were randomly assigned 1:1 to receive weekly subcutaneous albiglutide (30–50 mg, titrated based on glycemic response and tolerability) or matched placebo, added to standard care. Treatment assignment was masked via interactive voice/web response system. The primary endpoint was the first occurrence of cardiovascular death, myocardial infarction, or stroke, analyzed by intention-to-treat. A prespecified closed testing procedure first tested non-inferiority (upper 95% CI for HR <1.30), then superiority.
What this study cannot tell us
The median follow-up of 1.6 years was relatively short for a cardiovascular outcomes trial, so longer-term benefits or risks may not be captured. Albiglutide was subsequently withdrawn from the market for commercial reasons (not safety concerns), limiting the direct clinical applicability of these specific results — though the class-level evidence remains highly relevant. The trial enrolled patients with established cardiovascular disease, so results may not generalize to primary prevention populations. The dose range (30–50 mg) was fixed, and optimal dosing for cardiovascular benefit is unclear.
How to read the evidence
This is a large, well-designed, double-blind randomized controlled trial published in The Lancet with 9,463 participants across 28 countries. It represents the highest level of clinical evidence for a single trial. The prespecified statistical analysis plan and intention-to-treat approach further strengthen the evidence.
When this study was published
Published in 2018, this trial remains a cornerstone reference for GLP-1 receptor agonist cardiovascular benefits. Although albiglutide was commercially withdrawn in 2018, the class-level evidence continues to inform treatment guidelines and the development of newer GLP-1 agents.
The bigger picture
This trial joined a growing body of evidence from cardiovascular outcomes trials (LEADER, SUSTAIN-6, REWIND) showing that GLP-1 receptor agonists provide cardiovascular protection beyond glucose lowering. Together, these studies transformed how clinicians treat type 2 diabetes, shifting the focus from blood sugar targets to cardiovascular risk reduction. The GLP-1 class has since become one of the most important developments in both diabetes and cardiovascular medicine, with newer agents like semaglutide building on these foundational findings.
Questions still open
- Do the cardiovascular benefits of GLP-1 agonists extend to diabetic patients without established cardiovascular disease?
- What specific mechanisms beyond glucose lowering drive the cardiovascular protection seen with GLP-1 receptor agonists?
- Would longer treatment duration with GLP-1 agonists show even greater cardiovascular risk reduction?
Common questions
What is albiglutide and how does it relate to other GLP-1 drugs like semaglutide?
If albiglutide is no longer available, why does this study still matter?
Read the original research
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.
Lancet (London, England), 392(10157), 1519-1529
Citation
Hernandez, Adrian F; Green, Jennifer B; Janmohamed, Salim; D'Agostino, Ralph B; Granger, Christopher B; Jones, Nigel P; Leiter, Lawrence A; Rosenberg, Anne E; Sigmon, Kristina N; Somerville, Matthew C; Thorpe, Karl M; McMurray, John J V; Del Prato, Stefano. (2018). Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial.. Lancet (London, England), 392(10157), 1519-1529. https://doi.org/10.1016/S0140-6736(18)32261-X