No, Trulicity is Not the Only GLP-1 RA Approved for Primary Prevention of ASCVD
Multiple GLP-1 receptor agonists have demonstrated cardiovascular benefits and received FDA approval for cardiovascular risk reduction, not just dulaglutide (Trulicity). Specifically, four GLP-1 RAs have FDA approval for reducing cardiovascular events: liraglutide, semaglutide (subcutaneous), dulaglutide, and albiglutide (though albiglutide was withdrawn from the market for business reasons, not safety) 1.
FDA-Approved GLP-1 RAs for Cardiovascular Risk Reduction
The 2025 ADA Standards of Care explicitly states that four FDA-approved GLP-1 RAs have demonstrated statistically significant reductions in cardiovascular events 1:
- Liraglutide (LEADER trial): Reduced the primary composite outcome of MI, stroke, or CV death by 13% (HR 0.87, P=0.01 for superiority), with a 22% reduction in CV death specifically 1
- Semaglutide (subcutaneous): Showed cardiovascular benefits in moderate-sized clinical trials 1
- Dulaglutide (REWIND trial): Reduced major adverse cardiovascular events by 12% (HR 0.88, P=0.026) 1, 2
- Albiglutide: Demonstrated CV benefits but was removed from market for business reasons 1
The Primary Prevention Context
What makes dulaglutide somewhat unique is the composition of its trial population. The REWIND trial enrolled patients where only 31% had established cardiovascular disease at baseline, meaning 69% were in the primary prevention category (patients with multiple risk factors but no prior CV events) 2. This is a higher proportion of primary prevention patients compared to other GLP-1 RA cardiovascular outcome trials, which predominantly enrolled secondary prevention populations (>80% with established ASCVD in LEADER) 1.
However, this does not mean dulaglutide is the "only" agent approved for primary prevention. The FDA approvals and guideline recommendations apply to patients with either established ASCVD OR multiple cardiovascular risk factors 3.
Current Guideline Recommendations
The 2022 Canadian Cardiovascular Society guidelines make a Strong Recommendation with Moderate-Quality Evidence that in adults with T2DM and either established ASCVD or multiple risk factors for ASCVD, clinicians should use GLP-1 RAs (as a class) to reduce the risk of all-cause or CV mortality or MACE 3. This recommendation is not limited to dulaglutide alone.
Important Clinical Caveats
The evidence for pure primary prevention remains limited across all GLP-1 RAs. A 2026 systematic review found that only 26% of participants across GLP-1 RA cardiovascular outcome trials were primary prevention patients, and when analyzed separately, the pooled estimate for MACE in primary prevention was not statistically significant (HR 0.88,95% CI 0.74-1.05) with low certainty of evidence 4. This means the cardiovascular benefits are most clearly established in patients with established ASCVD, not purely primary prevention.
In clinical practice, prescribing patterns may not align with cardiovascular indications. Real-world data suggests GLP-1 RA use remains more strongly associated with glucose control intensity (particularly insulin use) rather than cardiovascular risk profiles, indicating underutilization based on CV indications 5.
Bottom Line for Clinical Practice
When selecting a GLP-1 RA for cardiovascular risk reduction in patients with T2DM:
- For established ASCVD: Choose liraglutide, semaglutide (subcutaneous), or dulaglutide—all have proven CV benefits 1, 3
- For primary prevention (multiple risk factors without prior CV events): The evidence is strongest for dulaglutide given the REWIND trial population composition 2, but guidelines support the class effect 3
- Consider GLP-1 RAs specifically for stroke reduction: This benefit appears most pronounced with GLP-1 RAs (16% relative risk reduction) compared to SGLT2 inhibitors 3