A new study compares GLP-1 receptor agonists with known cardiovascular benefits, dulaglutide and liraglutide, against each other, rather than against the traditional placebo.
Many studies compare glucagon-like peptide-1 (GLP-1) receptor agonists such as dulaglutide and liraglutide against placebos to investigate their potential impact on cardiovascular (CV) outcomes. However, literature involving head-to-head comparisons between GLP-1 receptor agonists in the realm of CV disease is limited. Previous studies from The Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial and the Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes (LEADER) trial have shown that both dulaglutide and liraglutide have beneficial CV outcomes when compared to placebo, respectively. Patients living with type 2 diabetes (T2D) are at a significantly increased risk of developing CV disease, leading to the potential need for a GLP-1 receptor agonist with clear CV benefits. Comparing medications that have already demonstrated CV benefits in patients with T2D (dulaglutide and liraglutide), will help shed some light on whether one therapy may be more advantageous than the other.
A retrospective cohort study by Bowe et al. was designed to compare CV outcomes, healthcare utilization, costs, and treatment discontinuation/persistence between dulaglutide and liraglutide. Baseline characteristics were balanced via propensity score matching (1:1) among the 2,294 patients in each cohort. The Humana Research Database was used as the data source for selecting eligible patients that were 18-89 years of age and who were treatment naïve to either drug six months before the index date. Patients were excluded from the study if claims for other GLP-1 receptor agonists were made on the index date. The primary CV outcome was a composite of myocardial infarction, stroke, or all-cause death. The secondary CV outcome was a composite of heart failure or all-cause death. Composite CV outcomes were calculated both overall and were stratified by patients with atherosclerotic disease (ASCVD) at baseline. Cox proportional hazard models were used to compare CV outcomes and treatment discontinuation. Wilcoxon signed-rank test was used to compare healthcare resource utilization and costs.
Results from the primary composite outcome with dulaglutide as the comparator and liraglutide as the reference showed HR 1.04 [95% CI 0.90 – 1.19] for the primary composite outcome overall, and HR 1.08 [95% CI 0.90 – 1.29] for the primary composite outcome in patients with established ASCVD. Results from the secondary composite outcome with dulaglutide as the comparator and liraglutide as the reference showed HR 0.91 [95% CI 0.79 – 1.05] for the secondary composite outcome overall, and HR 1.00 [95% CI 0.84 – 1.20] for the secondary composite outcome in patients with established ASCVD.
Treatment persistence results (percentage of patients) were in favor of dulaglutide (42.2%) vs. liraglutide (36.8%) with a p-value of <0.001. Similar results in favor of dulaglutide were seen with discontinuation of therapy with an HR 0.85 [95% CI 0.79 – 0.92] and a p-value of <0.001. There was no statistically significant difference for an inpatient stay (percentage of patients) between the dulaglutide (13.9%) and liraglutide (13.6%) groups (p=0.789). No statistically significant difference in emergency department visits (percentage of patients) was observed in the dulaglutide (26.3%) and liraglutide (26.1%) groups (p=0.890). The mean difference in pharmacy costs per person per month was significantly lower in the liraglutide group by $73 (p=0.047) compared to the dulaglutide group.
Based on the results of this study, there was no statistically significant difference in primary or secondary composite CV outcomes, nor was there any difference in outcomes when patients were stratified based on whether they were living with ASCVD or not. Interestingly, results were in favor of dulaglutide over liraglutide in having higher treatment persistence and less treatment discontinuation at higher pharmacy costs. Perhaps one of the most considerable limitations in this study was that CV outcomes were measured based on medical claims using diagnosis codes, which may not have represented new events. Further head-to-head research is warranted between other GLP-1 receptor agonists to help tease out whether significant differences in safety and efficacy exist between each agent. While no difference in CV outcomes was observed, the difference in persistence and discontinuation percentages in favor of dulaglutide over liraglutide may help persuade the use of one agent over the other.
- When compared to each other, dulaglutide and liraglutide have similar CV outcomes.
- Dulaglutide has higher treatment persistence and less treatment discontinuation than liraglutide, most likely due to once-weekly versus once-daily injections, respectively.
- Further research is needed to compare head-to-head CV outcomes among other GLP-1 receptor agonists.
Bowe, Andy, et al. “1428-P: Cardiovascular Outcomes with Dulaglutide vs. Liraglutide.” Diabetes, vol. 69, no. Supplement 1, 2020, doi:10.2337/db20-1428-p
Gerstein, Hertzel C et al. “Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial.” Lancet (London, England) vol. 394,10193 (2019): 121-130. doi:10.1016/S0140-6736(19)31149-3
Marso, Steven P et al. “Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.” The New England journal of medicine vol. 375,4 (2016): 311-22. doi:10.1056/NEJMoa160382
Lawand Kamal, PharmD Candidate 2021, Skaggs School of Pharmacy and Pharmaceutical Sciences