Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs
Authors: Mikhail Kosiborod, Carolyn S.P. Lam, Shun Kohsaka, Dae Jung Kim, Avraham Karasik, Jonathan Shaw, Navdeep Tangri, Su-Yen Goh, Marcus Thuresson, Hungta Chen, Filip Surmont, Niklas Hammar, Peter Fenici, Mikhail Kosiborod, Matthew A. Cavender, Alex Z. Fu, John P. Wilding, Kamlesh Khunti, Anna Norhammar, Kåre Birkeland, Marit Eika Jørgensen, Reinhard W. Holl, Carolyn SP Lam, Hanne Løvdal Gulseth, Bendix Carstensen, Esther Bollow, Josep Franch-Nadal, Luis Alberto García Rodríguez, Avraham Karasik, Navdeep Tangri, Shun Kohsaka, Dae Jung Kim, Jonathan Shaw, Suzanne Arnold, Su-Yen Goh, Niklas Hammar, Peter Fenici, Johan Bodegård, Hungta Chen, Filip Surmont, Kyle Nahrebne, Betina T. Blak, Eric T. Wittbrodt, Matthias Saathoff, Yusuke Noguchi, Donna Tan, Maro Williams, Hye Won Lee, Maya Greenbloom, Oksana Kaidanovich-Beilin, Khung Keong Yeo, Yong Mong Bee, Joan Khoo, Agnes Koong, Yee How Lau, Fei Gao, Wee Boon Tan, Hanis Abdul Kadir, Kyoung Hwa Ha, Jinhee Lee, Gabriel Chodick, Cheli Melzer Cohen, Reid Whitlock, Lucia Cea Soriano, Oscar Fernándex Cantero, Ellen Riehle, Jennie Ilomaki, Dianna Magliano
Journal: Journal of the American College of Cardiology (2018)

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.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.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.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.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).