DIET & NUTRITION 
PATIENT EDUCATION 
OBESITY/WEIGHT MANAGEMENT 
EXERCISE/TRAINING 
LEGAL MATTERS 
GUIDELINES/RECOMMENDATIONS 
This target trial emulation study analyzes real-world cardiovascular outcomes data from 703 clinical practices, comparing GLP-1 receptor agonists against SGLT-2 inhibitors over median 2.2-year follow-up. The observational design with propensity score matching provides moderate-quality evidence for clinical decision-making in diabetes management.
⚕️ Key Clinical Considerations ⚕️
- Semaglutide demonstrated 11% relative risk reduction for composite death/MI/stroke versus empagliflozin (HR 0.89, 95% CI 0.78-1.02), though confidence interval crosses null.
- Stroke risk showed significant 38% reduction with semaglutide (HR 0.62, 95% CI 0.43-0.89), representing strongest individual outcome benefit.
- Dulaglutide showed no cardiovascular advantage over empagliflozin (HR 1.03, 95% CI 0.90-1.16), suggesting class-specific rather than class-wide effects.
- Death and myocardial infarction risks were similar between semaglutide and empagliflozin groups, limiting overall composite outcome significance.
- Observational design introduces potential residual confounding despite propensity matching, requiring cautious interpretation of comparative effectiveness claims.
🎯 Clinical Practice Impact 🎯
- Patient Communication: Stroke prevention benefits with semaglutide provide compelling discussion point for patients with cerebrovascular risk factors, while emphasizing that overall cardiovascular benefits remain modest and require individualized risk assessment.
- Practice Integration: Results support preferential semaglutide selection over empagliflozin when stroke prevention is prioritized, though dulaglutide appears equivalent to SGLT-2 inhibitors for cardiovascular outcomes.
- Risk Management: Lack of cause-specific mortality data limits ability to counsel patients on specific death risk reduction, requiring focus on composite outcomes and stroke-specific benefits.
- Action Items: Consider patient-specific cardiovascular risk profiles when choosing between GLP-1 agonists, with semaglutide preferred for stroke-prone patients and dulaglutide reserved for other clinical indications.
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