Marwan Saad1, Ahmed N Mahmoud2, Islam Y Elgendy2, Ahmed Abuzaid3, Amr F Barakat4, Akram Y Elgendy2, Mohammad Al-Ani2, Amgad Mentias5, Ramez Nairooz6, Anthony A Bavry2, Debabrata Mukherjee7. 1. Department of Medicine, Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States. Electronic address: mssaad@uams.edu. 2. Department of Medicine, University of Florida, Gainesville, FL, United States. 3. Department of Medicine, Division of Cardiovascular Medicine, Jefferson University Hospital/Christiana Care Health System, Newark, DE, United States. 4. Department of Medicine, Cleveland Clinic Foundation, Cleveland, OH, United States. 5. Department of Medicine, Division of Cardiovascular Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, United States. 6. Department of Medicine, Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States. 7. Division of Cardiology, Texas Tech University Health Sciences Center, El Paso, TX, United States.
Abstract
BACKGROUND: The impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular outcomes in patients with type II diabetes mellitus (DM) is not well established. METHODS: We searched electronic databases from inception through July 2016 for randomized, placebo-controlled trials, involving SGLT-2 inhibitors. Fixed-effects summary odds ratios (OR) were constructed using Peto model. RESULTS: Eighty-one trials with a total of 37,195 patients were included. The mean follow-up was 89weeks. Compared with placebo, SGLT-2 inhibitors were associated with a lower risk of all-cause mortality (OR 0.72; 95% CI 0.59-0.86; P<0.001), cardiovascular mortality (OR 0.67; 95% CI 0.53-0.84; P=0.001), and heart failure (OR 0.67; 95% CI 0.51-0.87; P=0.003), but a similar risk of myocardial infarction (OR 0.89; 95% CI 0.74-1.09; P=0.29) and stroke/transient ischemic attack (OR 1.09; 95% CI 0.87-1.37; P=0.47). The reduction in all-cause mortality was noticed with empagliflozin (OR 0.66; 95% CI 0.54-0.81; P<0.001), but not with other SGLT-2 inhibitors (ORdapagliflozin 1.37; 95% CI 0.71-2.62; P=0.35; ORcanagliflozin 0.82; 95% CI 0.41-1.68; P=0.59; ORluseogliflozin 4.6; 95% CI 0.07-284.25; P=0.47; and ORipragliflozin 4.73; 95% CI 0.08-283.14; P=0.46) (Pinteraction=0.19). Potential harm was observed with dapagliflozin on cardiovascular mortality (OR 2.15, 95% CI 0.92-5.04, P=0.08). CONCLUSIONS: In patients with type II DM, SGLT-2 inhibitors appeared to reduce both all-cause and cardiovascular mortality, primarily due to reduction in the risk of heart failure. The benefit was only seen with empagliflozin. There was suggestion of potential harm with dapagliflozin, thus future trials are needed to ascertain the cardiovascular safety of other agents in this class.
BACKGROUND: The impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular outcomes in patients with type II diabetes mellitus (DM) is not well established. METHODS: We searched electronic databases from inception through July 2016 for randomized, placebo-controlled trials, involving SGLT-2 inhibitors. Fixed-effects summary odds ratios (OR) were constructed using Peto model. RESULTS: Eighty-one trials with a total of 37,195 patients were included. The mean follow-up was 89weeks. Compared with placebo, SGLT-2 inhibitors were associated with a lower risk of all-cause mortality (OR 0.72; 95% CI 0.59-0.86; P<0.001), cardiovascular mortality (OR 0.67; 95% CI 0.53-0.84; P=0.001), and heart failure (OR 0.67; 95% CI 0.51-0.87; P=0.003), but a similar risk of myocardial infarction (OR 0.89; 95% CI 0.74-1.09; P=0.29) and stroke/transient ischemic attack (OR 1.09; 95% CI 0.87-1.37; P=0.47). The reduction in all-cause mortality was noticed with empagliflozin (OR 0.66; 95% CI 0.54-0.81; P<0.001), but not with other SGLT-2 inhibitors (ORdapagliflozin 1.37; 95% CI 0.71-2.62; P=0.35; ORcanagliflozin 0.82; 95% CI 0.41-1.68; P=0.59; ORluseogliflozin 4.6; 95% CI 0.07-284.25; P=0.47; and ORipragliflozin 4.73; 95% CI 0.08-283.14; P=0.46) (Pinteraction=0.19). Potential harm was observed with dapagliflozin on cardiovascular mortality (OR 2.15, 95% CI 0.92-5.04, P=0.08). CONCLUSIONS: In patients with type II DM, SGLT-2 inhibitors appeared to reduce both all-cause and cardiovascular mortality, primarily due to reduction in the risk of heart failure. The benefit was only seen with empagliflozin. There was suggestion of potential harm with dapagliflozin, thus future trials are needed to ascertain the cardiovascular safety of other agents in this class.