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Войти в исследования Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM.
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Khera Rohan, Aminorroaya Arya, Dhingra Lovedeep Singh, Thangaraj Phyllis M, Pedroso Camargos Aline, Bu Fan, Ding Xiyu, Nishimura Akihiko, Anand Tara V, Arshad Faaizah, Blacketer Clair, Chai Yi, Chattopadhyay Shounak, Cook Michael, Dorr David A, Duarte-Salles Talita, DuVall Scott L, Falconer Thomas, French Tina E, Hanchrow Elizabeth E, Kaur Guneet, Lau Wallis C Y, Li Jing, Li Kelly, Liu Yuntian, Lu Yuan, Man Kenneth K C, Matheny Michael E, Mathioudakis Nestoras, McLeggon Jody-Ann, McLemore Michael F, Minty Evan, Morales Daniel R, Nagy Paul, Ostropolets Anna, Pistillo Andrea, Phan Thanh-Phuc, Pratt Nicole, Reyes Carlen, Richter Lauren, Ross Joseph S, Ruan Elise, Seager Sarah L, Simon Katherine R, Viernes Benjamin, Yang Jianxiao, Yin Can, You Seng Chan, Zhou Jin J, Ryan Patrick B, Schuemie Martijn J, Krumholz Harlan M, Hripcsak George, Suchard Marc A
Аннотация
OBJECTIVES: The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM.
METHODS: Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis.
RESULTS: Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13]).
CONCLUSIONS: In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD.