Article Impact Level: HIGH Data Quality: STRONG Summary of Journal of the American College of Cardiology, 84(10), 904–917. https://doi.org/10.1016/j.jacc.2024.05.069 Dr. Rohan Khera et al.
Points
- The LEGEND-T2DM study evaluated the cardiovascular efficacy of second-line antihyperglycemic agents—SGLT2 inhibitors, GLP-1 receptor agonists, DPP4 inhibitors, and sulfonylureas—in type 2 diabetes mellitus (T2DM) patients already on metformin monotherapy.
- The study analyzed data from 1,492,855 T2DM patients with cardiovascular disease (CVD) across ten international databases, covering 1992 to 2021.
- Using large-scale propensity score models and Cox proportional hazards models, the study estimated hazard ratios (HRs) for major adverse cardiovascular events (MACE) during 5.2 million patient-years of follow-up.
- SGLT2 inhibitors and GLP-1 receptor agonists significantly reduced the risk of both 3-point and 4-point MACE compared to DPP4 inhibitors and sulfonylureas, with hazard ratios indicating a lower risk of cardiovascular events.
- The results suggest that SGLT2 inhibitors and GLP-1 receptor agonists are effective second-line treatments for reducing cardiovascular risk in T2DM patients with established CVD. There is no significant difference in efficacy between the two drug classes.
Summary
The LEGEND-T2DM study sought to assess the comparative cardiovascular efficacy of second-line antihyperglycemic agents—specifically sodium-glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP4is), and sulfonylureas (SUs)—in patients with type 2 diabetes mellitus (T2DM) who were already on metformin monotherapy. Spanning data from 1992 to 2021 across ten international databases, the study included 1,492,855 patients with T2DM and cardiovascular disease (CVD), analyzing the impact of these medications on major adverse cardiovascular events (MACE).
The research methodology employed large-scale propensity score models to emulate a target trial in which pairwise comparisons among the four drug classes were analyzed. The study utilized Cox proportional hazards models to estimate hazard ratios (HRs) for both 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (including heart failure hospitalization). This meta-analysis was conducted over 5.2 million patient-years of follow-up, during which 25,982 instances of 3-point MACE and 41,447 of 4-point MACE were recorded.
The findings revealed that SGLT2is and GLP-1 RAs significantly reduced the risk of 3-point and 4-point MACE compared to DPP4is and SUs. Specifically, SGLT2is and GLP-1 RAs were associated with a lower risk of 3-point MACE compared to DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98], respectively) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88], respectively). DPP4is also showed a lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). No significant differences were found between SGLT2is and GLP-1 RAs in reducing MACE, suggesting that either could be effectively used as a second-line treatment in T2DM patients with established CVD.
Link to the article: https://www.sciencedirect.com/science/article/abs/pii/S0735109724077799
References Khera, R., Aminorroaya, A., Dhingra, L. S., Thangaraj, P. M., Pedroso Camargos, A., Bu, F., Ding, X., Nishimura, A., Anand, T. V., Arshad, F., Blacketer, C., Chai, Y., Chattopadhyay, S., Cook, M., Dorr, D. A., Duarte-Salles, T., DuVall, S. L., Falconer, T., French, T. E., … Suchard, M. A. (2024). Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM. Journal of the American College of Cardiology, 84(10), 904–917. https://doi.org/10.1016/j.jacc.2024.05.069
