{Reference Type}: Preprint
{Title}: Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study.
{Author}: Khera R;Aminorroaya A;Dhingra LS;Thangaraj PM;Camargos AP;Bu F;Ding X;Nishimura A;Anand TV;Arshad F;Blacketer C;Chai Y;Chattopadhyay S;Cook M;Dorr DA;Duarte-Salles T;DuVall SL;Falconer T;French TE;Hanchrow EE;Kaur G;Lau WC;Li J;Li K;Liu Y;Lu Y;Man KK;Matheny ME;Mathioudakis N;McLeggon JA;McLemore MF;Minty E;Morales DR;Nagy P;Ostropolets A;Pistillo A;Phan TP;Pratt N;Reyes C;Richter L;Ross J;Ruan E;Seager SL;Simon KR;Viernes B;Yang J;Yin C;You SC;Zhou JJ;Ryan PB;Schuemie MJ;Krumholz HM;Hripcsak G;Suchard MA;
{Journal}: medRxiv
{Volume}: 0
{Issue}: 0
{Year}: 2024 Feb 8
暂无{DOI}: 10.1101/2024.02.05.24302354
{Abstract}: <B>UNASSIGNED: </B>SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce 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 trials.<BR><B>UNASSIGNED: </B>Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis.<BR><B>UNASSIGNED: </B>Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]).<BR><B>UNASSIGNED: </B>In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD.<BR><B>UNASSIGNED: </B>National Institutes of Health, United States Department of Veterans Affairs.