November 20, 2023Cardiovascular DiabetologyOpen Access

Once-weekly glucagon-like peptide-1 receptor agonists vs dipeptidyl peptidase-4 inhibitors: cardiovascular effects in people with diabetes and cardiovascular disease

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Why the study?

GLP-1 RAs have proven cardiovascular benefits in T2D and ASCVD, but limited real-world evidence compares once-weekly GLP-1 RAs with DPP-4 inhibitors.

Does once-weekly GLP-1 receptor agonist therapy reduce the risk of ischemic stroke, MI, and healthcare costs compared to DPP-4 inhibitors in adults with T2D and established ASCVD?

Structured PICO

Does once-weekly GLP-1 receptor agonist therapy reduce the risk of ischemic stroke, MI, and healthcare costs compared to DPP-4 inhibitors in adults with T2D and established ASCVD?

Population

66,288 adults (unweighted; 64,971 weighted) with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD), mean age ~70 years, ~50% male, US-based (Optum Clinformatics Data Mart). Key inclusion: ≥2 separate diagnoses of T2D, ≥1 prescription for the index drug for ≥90 days, and history of ASCVD between 2001 and the index date.

Intervention

Once-weekly (OW) GLP-1 receptor agonists (exenatide, dulaglutide, or semaglutide) initiated between January 1, 2018, and June 30, 2021.

Comparator

Dipeptidyl peptidase-4 inhibitors (DPP-4is) (sitagliptin, saxagliptin, linagliptin, or alogliptin) initiated during the same period, with baseline characteristics balanced using inverse probability of treatment weighting (IPTW).

Outcome

Time to occurrence of ischemic stroke, myocardial infarction (MI), or their composite.composite

In adults with T2D and ASCVD, once-weekly GLP-1 receptor agonists are associated with significantly lower risks of ischemic stroke and MI, as well as reduced healthcare resource utilization and costs, compared to DPP-4 inhibitors.

Implication

May support preferring OW GLP-1 RAs over DPP-4is in T2D with ASCVD; leaves open need for RCTs to confirm.

Abstract

Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have proven cardiovascular benefits, are recommended in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, there is limited real-world evidence comparing the effects of once-weekly (OW) GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). This observational cohort study (1/1/2017–9/30/2021) used data from the Optum Clinformatics ® Data Mart to compare time to incident clinical cardiovascular outcomes, health care resource utilization (HCRU), and medical costs in new adult users of OW GLP-1 RAs and DPP-4is with T2D and ASCVD. Methods Time to occurrence of ischemic stroke, myocardial infarction (MI), or their composite and ASCVD-related and all-cause HCRU and medical costs were investigated. Baseline characteristics were balanced using inverse probability of treatment weighting. Survival analyses were conducted to compare risks during exposure. Results OW GLP-1 RA users (weighted N = 25,287) had 26%, 22%, and 24% lower risk of ischemic stroke, MI, and their composite, respectively, compared with DPP-4i users (weighted N = 39,684; all P < 0.01). Compared with DPP-4i users, OW GLP-1 RA users had 25% and 26% lower ASCVD-related and all-cause hospitalization costs, 19% and 23% lower ASCVD-related and all-cause medical costs, 23% and 27% fewer ASCVD-related and all-cause hospitalizations, 13% and 8% fewer ASCVD-related and all-cause outpatient visits, and 8% fewer all-cause ER visits (all P < 0.01). Conclusions In adults with T2D and ASCVD, OW GLP-1 RAs are associated with reduced stroke and MI risks and ASCVD-related and all-cause HCRU and costs vs DPP-4is.