Clinical bottom line
Early initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) is associated with improved cardiovascular outcomes, including reduced major adverse cardiovascular events. Despite guideline recommendations supporting their use, real-world data reveal substantial underutilization, particularly influenced by sex and socioeconomic disparities. Clinicians should consider earlier adoption of GLP-1 RAs in eligible patients with T2D and ASCVD to optimize cardiovascular risk reduction, while being mindful of barriers to equitable access.
What the evidence shows
GLP-1 receptor agonists have emerged as important agents in the management of T2D with concomitant ASCVD due to their demonstrated cardiovascular benefits beyond glycemic control. Randomized controlled trials have established that GLP-1 RAs reduce rates of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, in this high-risk population.
However, Scheen et al. (2024) highlight a paradoxical underuse of GLP-1 RAs in real-world clinical practice among patients with T2D and ASCVD, despite clear evidence and guideline endorsements. Their epidemiological analysis reveals that initiation of GLP-1 RAs often occurs late or not at all in eligible patients, potentially missing a critical window for cardiovascular risk modification.
Further insights from a comprehensive nationwide cohort study (2026) underscore that initiation rates of GLP-1 RAs vary significantly by sex and socioeconomic status. Women and individuals from lower socioeconomic backgrounds are less likely to be started on these agents, suggesting systemic disparities in access or prescribing patterns. These findings raise important considerations about equity in cardiovascular risk management and the need for targeted interventions to address these gaps.
Caveats and uncertainty
While the cardiovascular benefits of GLP-1 RAs are well documented in randomized trials, translating these findings into routine clinical practice remains challenging. Observational data on underuse and disparities are hypothesis-generating and may be influenced by confounding factors such as comorbidities, patient preferences, and healthcare system variables.
The optimal timing for initiation of GLP-1 RAs in the course of T2D and ASCVD is not definitively established. Most clinical trials enrolled patients with established disease, leaving uncertainty about benefits in earlier stages or primary prevention settings. Additionally, cost, tolerability, and patient adherence impact real-world effectiveness and require further study.
The socioeconomic and sex-based disparities identified warrant cautious interpretation. These differences may reflect complex interactions of healthcare access, provider biases, and patient-level factors that are not fully elucidated. More granular data and prospective studies are needed to understand and mitigate these inequities.
How this may change practice
Clinicians managing patients with T2D and ASCVD should be vigilant about early consideration of GLP-1 RAs as part of comprehensive cardiovascular risk reduction strategies. Awareness of the underutilization highlighted by Scheen et al. (2024) may prompt more proactive prescribing aligned with current guidelines.
Addressing disparities in initiation requires a multifaceted approach, including clinician education, system-level interventions to improve access, and patient engagement to overcome barriers related to socioeconomic status and sex. Incorporating routine assessment of eligibility for GLP-1 RAs during diabetes and cardiovascular care visits may help close the treatment gap.
Ultimately, earlier and equitable use of GLP-1 RAs has the potential to improve cardiovascular outcomes in a high-risk population, but implementation must be tailored to individual patient contexts and healthcare environments.