Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs Academic Article uri icon

abstract

  • BACKGROUND:Randomized trials demonstrated a lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high CV risk. Prior real-world data suggested similar SGLT-2i effects in T2D patients with a broader risk profile, but these studies focused on heart failure and death and were limited to the United States and Europe. OBJECTIVES:The purpose of this study was to examine a broad range of CV outcomes in patients initiated on SGLT-2i versus other glucose-lowering drugs (oGLDs) across 6 countries in the Asia Pacific, the Middle East, and North American regions. METHODS:New users of SGLT-2i and oGLDs were identified via claims, medical records, and national registries in South Korea, Japan, Singapore, Israel, Australia, and Canada. Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching. Hazard ratios (HRs) for death, hospitalization for heart failure (HHF), death or HHF, MI, and stroke were assessed by country and pooled using weighted meta-analysis. RESULTS:After propensity-matching, there were 235,064 episodes of treatment initiation in each group; ∼27% had established CV disease. Patient characteristics were well-balanced between groups. Dapagliflozin, empagliflozin, ipragliflozin, canagliflozin, tofogliflozin, and luseogliflozin accounted for 75%, 9%, 8%, 4%, 3%, and 1% of exposure time in the SGLT-2i group, respectively. Use of SGLT-2i versus oGLDs was associated with a lower risk of death (HR: 0.51; 95% confidence interval [CI]: 0.37 to 0.70; p < 0.001), HHF (HR: 0.64; 95% CI: 0.50 to 0.82; p = 0.001), death or HHF (HR: 0.60; 95% CI: 0.47 to 0.76; p < 0.001), MI (HR: 0.81; 95% CI: 0.74 to 0.88; p < 0.001), and stroke (HR: 0.68; 95% CI: 0.55 to 0.84; p < 0.001). Results were directionally consistent across both countries and patient subgroups, including those with and without CV disease. CONCLUSIONS:In this large, international study of patients with T2D from the Asia Pacific, the Middle East, and North America, initiation of SGLT-2i was associated with a lower risk of CV events across a broad range of outcomes and patient characteristics. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614).

authors

  • Kosiborod, Mikhail
  • Lam, Carolyn SP
  • Kohsaka, Shun
  • Kim, Dae Jung
  • Karasik, Avraham
  • Shaw, Jonathan
  • Tangri, Navdeep
  • Goh, Su-Yen
  • Thuresson, Marcus
  • Chen, Hungta
  • Surmont, Filip
  • Hammar, Niklas
  • Fenici, Peter
  • Kosiborod, Mikhail
  • Cavender, Matthew A
  • Fu, Alex Z
  • Wilding, John P
  • Khunti, Kamlesh
  • Norhammar, Anna
  • Birkeland, Kåre
  • Jørgensen, Marit Eika
  • Holl, Reinhard W
  • Lam, Carolyn SP
  • Gulseth, Hanne Løvdal
  • Carstensen, Bendix
  • Bollow, Esther
  • Franch-Nadal, Josep
  • García Rodríguez, Luis Alberto
  • Karasik, Avraham
  • Tangri, Navdeep
  • Kohsaka, Shun
  • Kim, Dae Jung
  • Shaw, Jonathan
  • Arnold, Suzanne
  • Goh, Su-Yen
  • Hammar, Niklas
  • Fenici, Peter
  • Bodegård, Johan
  • Chen, Hungta
  • Surmont, Filip
  • Nahrebne, Kyle
  • Blak, Betina T
  • Wittbrodt, Eric T
  • Saathoff, Matthias
  • Noguchi, Yusuke
  • Tan, Donna
  • Williams, Maro
  • Lee, Hye Won
  • Greenbloom, Maya
  • Kaidanovich-Beilin, Oksana
  • Yeo, Khung Keong
  • Bee, Yong Mong
  • Khoo, Joan
  • Koong, Agnes
  • Lau, Yee How
  • Gao, Fei
  • Tan, Wee Boon
  • Kadir, Hanis Abdul
  • Ha, Kyoung Hwa
  • Lee, Jinhee
  • Chodick, Gabriel
  • Melzer Cohen, Cheli
  • Whitlock, Reid
  • Cea Soriano, Lucia
  • Fernándex Cantero, Oscar
  • Riehle, Ellen
  • Ilomaki, Jennie
  • Magliano, Dianna

publication date

  • 2018