Comparative cardiovascular outcomes of semaglutide to dulaglutide in patients with type 2 diabetes.
This retrospective observational study used the TriNetX database of de-identified electronic health records (January 2018–December 2020) to compare cardiovascular outcomes between semaglutide and dulaglutide in adults with type 2 diabetes. From a pool of nearly 4.7 million patients with type 2 diabetes, 231,075 semaglutide initiators and 189,103 dulaglutide initiators were identified. Propensity score matching yielded 171,105 patients per group. Over a 3-year follow-up, the study found that semaglutide was associated with statistically significantly lower rates of all-cause death (4.2% vs. 5.6%; HR 0.75, 95% CI 0.72–0.78), acute myocardial infarction (5.2% vs. 5.6%; HR 0.94), stroke (5.8% vs. 6.4%; HR 0.90), and acute heart failure hospitalization (5.3% vs. 6.1%; HR 0.88) compared with dulaglutide. Key limitations include the observational, non-randomized design, which is susceptible to residual confounding despite propensity score matching; reliance on administrative/EHR coding for outcome ascertainment; and the inability to distinguish between semaglutide formulations (oral vs. injectable) or account for dosing differences between agents.
Why this grade: Although the study is large and uses propensity score matching in humans, its retrospective observational design with inherent residual confounding prevents it from establishing causality, limiting it to a "limited-human" evidence grade.
Type 2 diabetes significantly increases cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce major adverse cardiovascular events, heart failure hospitalizations, and death. However, the comparison among GLP-1 RAs on cardiovascular outcomes is limited. We compared all-cause death and cardiovascular events in patients using semaglutide or dulaglutide in patients with type 2 diabetes. This retrospective observational study used the TriNetX database of deidentified electronic medical records from January 1, 2018, to December 31, 2020. We identified 4,691,652 patients with type 2 diabetes, among whom 231,075 initiated semaglutide and 189,103 initiated dulaglutide. After propensity score matching, 171,105 patients were included in each group. The primary outcome measure was all-cause death during the 3-year follow-up period.; secondary outcomes were acute myocardial infarction, stroke, and acute heart failure.Over 3 years, the risk for all-cause death in patients who received semaglutide relative to those who received dulaglutide was significantly lower (4.2% vs. 5.6%, p < 0.001; hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.72-0.78). Similarly, patients who received semaglutide were less likely to have acute myocardial infarction (5.2% vs. 5.6%; HR, 0.94; 95% CI, 0.91-0.97; p < 0.001), stroke (5.8% vs. 6.4%; HR, 0.90; 95% CI, 0.87-0.93; p < 0.001), and acute heart failure (5.3% vs. 6.1%; HR, 0.88; 95% CI, 0.85-0.91; p < 0.001).In this multicenter, retrospective, observational study, semaglutide was associated with lower 3-year risks of all-cause death, acute myocardial infarction, stroke, and acute heart failure compared with dulaglutide in patients with type 2 diabetes.
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