Study title: Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes
Study title acronym: DECLARE-TIMI 58
ClinicalTrials.gov identifier: NCT01730534
1. Wiviott SD, Raz I, Mosenzon O, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357.
2. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
Study design: Multicenter, randomized, placebo-controlled trial in patients with type 2 diabetes with known cardiovascular disease or at risk for atherosclerotic cardiovascular disease were randomized to receive dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), or placebo. All patients in the study were given usual care for diabetes and cardiovascular risk factors such as antihypertensive and lipid-lowering medications.
Primary outcomes: Major adverse cardiovascular outcomes (MACE) and a composite of cardiovascular death or hospitalization from heart failure.
Other outcomes: Composite of adverse renal outcome (sustained 40% decrease in estimated glomerular filtration rate, development of end-stage renal disease, death from a renal cause) and all-cause mortality.
Results: Over 17,000 patients were included in the study; 10,186 patients had no history of cardiovascular disease. Dapagliflozin did not result in a lower rate of MACE (8.8% in the dapagliflozin group vs. 9.4% in the placebo group, P=0.17). Dapagliflozin did result in a lower rate of hospitalization from heart failure (HR of 0.73; 95% CI, 0.61 to 0.88). Dapagliflozin also showed a small reduction in adverse renal events (4.3% of the dapagliflozin group versus 5.6% in the placebo group, HR of 0.76; 95% CI 0.67-0.87). Adverse reactions that were more common in the dapagliflozin group included diabetic ketoacidosis (0.3% in the dapagliflozin group versus 0.1% in the placebo group) and genital infections (0.9% in the dapagliflozin group versus 0.1% in the placebo group).
Summary: This study showed that dapagliflozin did not reduce MACE in patients with type 2 diabetes at high risk of cardiovascular events. However, dapagliflozin reduced the rate of hospitalization from heart failure and showed a trend toward a decrease in adverse renal outcomes. Among SGLT2i medications, empagliflozin is the only medication that has demonstrated a reduction in cardiovascular events in adults with type 2 diabetes. It is unclear why other SGLT2 inhibitors, like canagliflozin and dapagliflozin, have not shown a reduction in cardiovascular events. Perhaps decreased cardiovascular events are isolated only to empagliflozin, or maybe differences in study design explain why other SGLT2i treatment has not shown a reduction in cardiovascular events.
This column highlights clinical trial data and landmark trials. Information for obtaining trial data and the references to the published articles are provided to facilitate discussion with your patients/colleagues. The trial is identified by the acronym and the National Clinical Trials Identifier. Primary outcome results are summarized.
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About our experts: Kathryn Thrailkill, MD, Professor of Pediatrics, Division of Pediatric Endocrinology, Barnstable Brown Endowed Chair in Pediatric Diabetes Research, Barnstable Brown Diabetes Center, University of Kentucky, Lexington, Kentucky
Derick Adams, DO, Assistant professor, internal medicine, Division of Endocrinology, Endocrinology Fellowship associate program director, Barnstable Brown Diabetes Center, University of Kentucky, Lexington, Kentucky