Lead Investigator: Joao Pedro Ferreira, Porto University
Title of Proposal Research: The impact of albiglutide on heart failure outcomes among patients with type 2 diabetes with and without heart failure at baseline
Vivli Data Request: 7609
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Type 2 diabetes is a condition that affects the regulation of glucose in the body and has many deleterious consequences to the organism. Cardiovascular complications, including heart failure (HF) are common in patients with diabetes. The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. Prevalence has been rising more rapidly in low- and middle-income countries than in high-income countries. Between 2000 and 2016, there was a 5% increase in premature mortality from diabetes. In 2019, diabetes was the ninth leading cause of death with an estimated 1.5 million deaths directly caused by diabetes.
Patients with type 2 diabetes (T2D) have a high risk of heart failure (HF) events. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (a drug class that lowers blood sugar levels by reducing the amount of glucose being absorbed by the kidneys so that it passes out in greater amounts in urine), have been shown to reduce HF events by 30-35%. On the other hand, glucagon-like peptide 1 receptor agonists (GLP-1Ra) (a drug class that increases the production of insulin by the pancreas, particularly after meals, which then regulates the amount of glucose in the blood), have been shown to reduce the risk of myocardial infarction and stroke, but may have a smaller magnitude effect on HF events (around 10% relative reduction). Consequently, uncertainty remains about the HF effects of GLP-1Ra, particularly among patients with established HF. As GLP1-Ra may increase heart rate, these agents may not be beneficial to patients with established HF; however, this clinically important hypothesis has not been adequately explored using prospective randomized data.
Albiglutide is a GLP-1Ra which is sufficiently longacting to be injected weekly.
The cardiovascular safety and efficacy of albiglutide was tested in the Harmony Outcomes trial, that enrolled patients with type 2 diabetes and cardiovascular disease. Heart failure outcomes, particularly among patients with HF history have not been fully explored.
The present proposal aims to study the impact of albiglutide on heart failure (HF) outcomes among patients with type 2 diabetes, with and without HF at baseline (i.e., prior to randomization). Heart failure is a common complication of diabetes, which is associated with poor quality of life and a poor prognosis. The effect of GLP-1Ra, like albiglutide, on HF outcomes is uncertain. This proposal aims to fill this gap in knowledge by studying the efficacy and safety of albiglutide on HF outcomes in patients with type 2 diabetes and a high cardiovascular risk participating in the Harmony Outcomes trial.
Statistical Analysis Plan:
We selected the Harmony Outcomes trial because it is a large outcomes trial testing the effect of a GLP1-Ra (albiglutide) vs. placebo in patients with type 2 diabetes and a high cardiovascular risk. A large international trial including more than 9400 patients provides an unique opportunity to test the efficacy and safety of albiglutide regarding HF outcomes, according to HF status at baseline.
Baseline characteristics will be compared between patients with and without HF at baseline with proportions, means or medians according to each variable characteristic using the appropriate statistical tests.
Time-to-event analyses of HF outcomes outcomes will be assessed in the intention-to-treat population by use of Cox proportional hazards regression, with treatment group as explanatory variable. The analysis will be performed within subgroups of patients with and without HF at baseline and the treatment effect differences will be assessed with treatment-by-HF status interaction terms. The Kaplan-Meier method will used to estimate event rates.
No adjustment for multiplicity is prespecified, as this proposal is exploratory. No data inputation will be performed i.e., a complete case analysis will be done.
Requested Studies:
A Long Term, Randomised, Double Blind, Placebo-controlled Study to Determine the Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Patients With Type 2 Diabetes Mellitus
Data Contributor: GlaxoSmithKline
Study ID: NCT02465515
Sponsor ID: GLP116174
Public Disclosures:
Ferreira JP, Sharma A, Vasques-Nóvoa F, Angélico-Gonçalves A, Leite AR, Borges-Canha M, Carvalho D, Packer M, Zannad F, Leite-Moreira A, Neves JS. Albiglutide in patients with type 2 diabetes and heart failure: a post-hoc analysis from Harmony Outcomes. Eur J Heart Fail. 2022 Aug 23. doi: 10.1002/ejhf.2660