Christopher P Cannon1, Darren K McGuire2, Richard Pratley3, Sam Dagogo-Jack4, James Mancuso5, Susan Huyck6, Bernard Charbonnel7, Weichung J Shih8, Silvina Gallo9, Urszula Masiukiewicz5, Gregory Golm6, Francesco Cosentino10, Brett Lauring6, Steven G Terra11. 1. Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Baim Institute for Clinical Research, Boston, MA. Electronic address: cpcannon@bwh.harvard.edu. 2. University of Texas Southwestern Medical Center, Dallas, TX. 3. Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando, FL. 4. University of Tennessee Health Science Center, Memphis, TN. 5. Pfizer Inc., Groton, CT. 6. Merck & Co., Inc., Kenilworth, NJ. 7. University of Nantes, France. 8. Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey, New Brunswick NJ. 9. Pfizer Inc., Berlin, Germany. 10. Unit of Cardiology, Karolinska University Hospital Solna, Stockholm, Sweden. 11. Pfizer Inc., Andover, MA.
Abstract
BACKGROUND:Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), approved in the United States and European Union to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular (CV) outcomes trial (NCT01986881) has a primary objective to demonstrate non-inferiority of ertugliflozin versus placebo on major adverse CV events: time to the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary objectives are to demonstrate superiority of ertugliflozin versus placebo on time to: 1) the composite outcome of CV death or hospitalization for heart failure (HF); 2) CV death; and 3) the composite outcome of renal death, dialysis/transplant, or doubling of serum creatinine from baseline. METHODS:Patients ≥40 years old with T2DM (HbA1c 7.0-10.5%) and established atherosclerotic cardiovascular disease (ASCVD) of the coronary, cerebral, and/or peripheral arterial systems, were randomized 1:1:1 to once daily double-blind placebo, ertugliflozin 5 mg or 15 mg added to existing therapy. RESULTS:8246 patients were randomized and 8238 received at least 1 dose of investigational product. Mean age was 64.4 years, 11.0% were ≥75 years old, and mean diabetes duration was 12.9 years with screening HbA1c of 8.3%. At entry, coronary artery disease, cerebrovascular disease, and peripheral arterial disease were present in 76.3%, 23.1%, and 18.8% of patients, respectively. HF was present in 23.1%, and Stage 3 kidney disease in 21.6% of patients. CONCLUSION: The results from the VERTIS-CV trial will define the CV and renal safety and efficacy of ertugliflozin in patients with T2DM and ASCVD.
RCT Entities:
BACKGROUND:Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), approved in the United States and European Union to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular (CV) outcomes trial (NCT01986881) has a primary objective to demonstrate non-inferiority of ertugliflozin versus placebo on major adverse CV events: time to the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary objectives are to demonstrate superiority of ertugliflozin versus placebo on time to: 1) the composite outcome of CV death or hospitalization for heart failure (HF); 2) CV death; and 3) the composite outcome of renal death, dialysis/transplant, or doubling of serum creatinine from baseline. METHODS:Patients ≥40 years old with T2DM (HbA1c 7.0-10.5%) and established atherosclerotic cardiovascular disease (ASCVD) of the coronary, cerebral, and/or peripheral arterial systems, were randomized 1:1:1 to once daily double-blind placebo, ertugliflozin 5 mg or 15 mg added to existing therapy. RESULTS: 8246 patients were randomized and 8238 received at least 1 dose of investigational product. Mean age was 64.4 years, 11.0% were ≥75 years old, and mean diabetes duration was 12.9 years with screening HbA1c of 8.3%. At entry, coronary artery disease, cerebrovascular disease, and peripheral arterial disease were present in 76.3%, 23.1%, and 18.8% of patients, respectively. HF was present in 23.1%, and Stage 3 kidney disease in 21.6% of patients. CONCLUSION: The results from the VERTIS-CV trial will define the CV and renal safety and efficacy of ertugliflozin in patients with T2DM and ASCVD.
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Authors: Katherine R Tuttle; Frank C Brosius; Matthew A Cavender; Paola Fioretto; Kevin J Fowler; Hiddo J L Heerspink; Tom Manley; Darren K McGuire; Mark E Molitch; Amy K Mottl; Leigh Perreault; Sylvia E Rosas; Peter Rossing; Laura Sola; Volker Vallon; Christoph Wanner; Vlado Perkovic Journal: Diabetes Date: 2020-10-26 Impact factor: 9.461