Combination GIP/GLP-1 Agonism More Effectively Prevents Cardiovascular Events

According to a new study, tirzepatide, a dual gastric inhibitory peptide/glucagon-like peptide-1 (GIP/GLP-1) receptor co-agonist, may have better outcomes in treating sleep apnea in patients with obesity than solely GLP-1 receptor agonists like liraglutide.1

Presented at the 9th Annual Heart in Diabetes conference by Ekow Essien, MD, an internal medicine resident at Advocate Aurora Health, this retrospective cohort study directly compares mortality and cardiovascular outcomes between patients with obesity and sleep apnea treated with tirzepatide versus liraglutide.1

Tirzepatide was the first dual GIP/GLP-1 receptor co-agonist approved for treating type 2 diabetes mellitus (T2DM) in the US. An acylated peptide designed to activate the GIP and GLP-1 receptors, which are key mediators of insulin secretion, tirzepatide is also often expressed in the regions of the brain which regulate food intake.2

Liraglutide is an acylated GLP-1 analogue with 97% amino acid homology with native GLP-1. It is widely used to treat T2DM, administered via daily subcutaneous injection. Its effects are protracted; release from the injection site is slowed and the drug exhibits a reduced elimination rate due to metabolic stabilization and reduced renal filtration.3

Both medications are also efficacious in preventing cardiovascular events and related mortality, as both are directly connected to obesity. However, there is little data in the literature contrasting their efficacy. The team noted this as the central purpose of the study.

“Both tirzepatide and liraglutide have demonstrated cardiometabolic benefits, but their comparative cardiovascular outcomes in high-risk populations remain poorly characterized,” wrote Essien and colleagues.1

Investigators collected data on 42,712 patients with obesity and sleep apnea from the TriNetX Global Collaborative Network. Patients were defined as obese if their BMI was ≥30 kg/m2. Patients were prescribed either tirzepatide or liraglutide – both cohorts consisted of 21,356 patients. The primary outcome of the study was listed as all-cause mortality; secondary outcomes included cardiac events, arrhythmias, and other clinical outcomes.1

By the end of the study, the tirzepatide cohort exhibited an all-cause mortality of .7% compared to liraglutide’s 1.4% (both HR, .479; 95% CI, .394-.582, P <.001). Heart failure (HR, 0.658; 95% CI, .583-.743), atrial fibrillation (HR, .706; 95% CI, .605-.823), ventricular tachycardia (HR, .749; 95% CI, .585-.958), and cerebrovascular disease (HR, .781; 95% CI, .683-.893) also exhibited lower risk with tirzepatide. Notably, the medication also exhibited lower risk of acute kidney injury, reduced hypertension, lower incidence of coronary artery disease, and reduced peripheral arterial disease.1

Essien and colleagues noted that tirzepatide use was associated with substantially lower all-cause mortality than liraglutide – tirzepatide exhibited a 52% reduction in all-cause mortality, which suggest potential cardiovascular advantages of GIP/GLP-1 receptor agonism over GLP-1 receptor agonism alone.1

The team did note some limitations to the study, including its retrospective design, its potential residual confounding, and unknown medication adherence. However, the results of the trial still indicate the inherent superiority of utilizing GIP/GLP-1 receptor agonists to GLP-1 receptor agonists.1

References

1. Essien E, Nwaezeapu K, Agyekum A, et al. Comparative Cardiovascular Outcomes of Tirzepatide vs Liraglutide in Obese Patients with Sleep Apnea. Abstract presented at the 9th Annual Heart in Diabetes Conference in Philadelphia, PA from June 6-8 2025.

2. Nauck MA, D'Alessio DA. Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Cardiovasc Diabetol. 2022;21(1):169. Published 2022 Sep 1. doi:10.1186/s12933-022-01604-7

3. Jacobsen LV, Flint A, Olsen AK, Ingwersen SH. Liraglutide in Type 2 Diabetes Mellitus: Clinical Pharmacokinetics and Pharmacodynamics. Clin Pharmacokinet. 2016;55(6):657-672. doi:10.1007/s40262-015-0343-6