| Title: |
Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes: A Multinational, Federated Analysis of LEGEND-T2DM |
| Authors: |
Khera, R; Aminorroaya, A; Singh Dhingra, L; Thangaraj, PM; Pedroso Camargos, A; Bu, F; Ding, X; Nishimura, A; Anand, TV; Arshad, F; Blacketer, C; Chai, Y; Chattopadhyay, S; Cook, M; Dorr, DA; Duarte-Salles, T; DuVall, S; Falconer, T; French, TE; Hanchrow, EE; Kaur, G; Lau, WCY; Li, J; Li, K; Liu, Y; Lu, Y; Man, KKC; Matheny, MuE; Mathioudakis, N; McLeggon, JA; McLemore, MF; Pistillo, A; Phan, TP; Pratt, N; Reyes, C; Richter, L; Ross, J; Ruan, E; Seager, SL; Simon, AA; Viernes, B; Yang, J; Yin, C; You, CS; Zhou, JJ; Ryan, PB; Schuemie, MJ; Krumholz, HM; Hripcsak, G; Suchard, MA |
| Source: |
Journal of the American College of Cardiology , 84 (10) pp. 904-917. (2024) |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Cardiovascular diseases; comparative effectiveness research; glucagon-like peptide-1 receptor agonists; hypoglycemic agents; sodium-glucose transporter 2 inhibitors; type 2 diabetes mellitus |
| Description: |
Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials. // 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10193001/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10193001/1/Man_Comparative%20Effectiveness%20of%20Second-line%20Antihyperglycemic%20Agents%20for%20Cardiovascular%20Outcomes-%20A%20Multinational,%20Federated%20Analysis%20of%20LEGEND-T2DM_AAM.pdf; https://discovery.ucl.ac.uk/id/eprint/10193001/ |
| Rights: |
open |
| Accession Number: |
edsbas.FD239907 |
| Database: |
BASE |