Study looks at convenient once-weekly GLP-1 that can reduce chances of heart attacks and strokes.
It is well known that the risk of a cardiovascular events is higher in patients with type 2 diabetes. The new hyperglycemia guidelines for 2018 strongly advise to incorporate an SGLT-2 inhibitor into a patient’s therapy to decrease the risk of a cardiovascular event.
However, the guideline lists GLP-1 agonists only as an alternative when SGLT-2 inhibitors are contraindicated because the evidence of protection from a cardiovascular event has been inconsistent. The Harmony Outcomes trial was randomized, double-blinded, event driven, and studied the cardiovascular safety and efficacy of albiglutide in people with type 2 diabetes who have cardiovascular disease.
The study included men and women with type 2, from 28 countries, over 40 years of age, with established coronary, cerebrovascular or peripheral arterial disease, and an A1C greater then 7.0%. Patients were randomized on a 1:1 ratio to either albiglutide or placebo.
Patients were started on 0.5 ml once weekly, and adjusted after five weeks if the patient needed better glycemic management. If blood sugar goals were still not met, other glucose-lowering medications were either adjusted or added on. The primary outcomes the study looked at were death from cardiovascular causes, heart attack, or stroke. There were a large variety of secondary outcomes ranging from cardiovascular and metabolic outcomes to safety outcomes. Hazard ratios of 1.00 to 1.30 indicated non-inferiority, while less than 1.00 indicated superiority. Cox proportional hazards regression and Kaplan-Meier method were also used.
There were 9,463 participants who were divided into the albiglutide or placebo group, with 71% of them having coronary artery disease. Patients would report every 4 months until the projected 611 events took place to give the study sufficient power. At the time the study ended in 2018, 50% of the albiglutide group were taking the maximum dose of 50 mg. With equal groups the primary endpoint occurred in 338 patients from the albiglutide group, and in 428 patients in the placebo group. The event rates of events per 100 person-years were 4.57 albiglutide to 5.87 placebo. The hazard ratio was 0.78 (95% CI of 0.68-0.90). This hazard ratio indicates that albiglutide is both non-inferior and superior to the placebo in efficacy, especially in the myocardial infarction subgroup. The secondary endpoints overall also looked better in the albiglutide group. Notably the A1C was -0.63% lower in the albiglutide group then in placebo. However, there was no protection factor in hospitalization due to heart failure, a condition which can develop with the use of some glucose-lowering medications. There were three deaths in the placebo group vs two in the albiglutide group.
In patients with type 2 diabetes, albiglutide reduced heart attacks and strokes by 22%. There was not a significant decrease in cardiovascular deaths seen with this and previous GLP-1 studied, but they did reduce atherothrombotic events via an unknown mechanism. Albiglutide also had a delay in risk reduction but showed that the risk grew smaller the longer the medication was taken. Significantly the placebo group had to have additional glucose-lowering medications prescribed more often than the albiglutide group and thus had more hypoglycemia.
This study did have some limitation, one being that local guidelines were used to define range of blood sugar, these could be different based on what country the patient was in.
This study did not measure biomarkers and had short duration of follow up. The follow ups only lasted as long as needed to provide the correct power to the study only a few short years rather than 5-10 year studies, which provide a better insight. Overall, this is a convenient once-weekly injection, which can have some potentially lifesaving effects.
Albiglutide decreased the risk of cardiovascular events in patients with T2D and cardiovascular events with good safety and efficacy.
- Guidelines prefer SGLT-2 inhibitors to GLP-1 agonist for reducing risk of cardiovascular events. This study found that given once weekly, albiglutide can reduce the risk of heart attacks and strokes by 22%.
- There is a lower chance of hypoglycemia with albiglutide since prescribers don’t have to adjust or add other glucose-lowering medication, which could cause hypoglycemia.
- Although this study was short, it analyzed patients from 28 counties so there is no need to study different populations, but longer studies may reveal long-term effects not seen in this study.
Hernandez, Adrian F, et al. “Albiglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease (Harmony Outcomes): a Double-Blind, Randomised Placebo-Controlled Trial.” The Lancet, 2 Oct. 2018, doi:10.1016/s0140-6736(18)32261-x.
Davies, Melanie J., et al. “Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).” Diabetes Care, 2018, p. dci180033., doi:10.2337/dci18-0033.
Arsalan Hashmi, Pharm. D. Candidate 2019, LECOM School of Pharmacy