There was potential bias due to early discontinuation.Serious Adverse Events 34.1% Dapagliflozin vs 36.2% Placebo (CI 0.87-0.96) Adverse event leading to discontinuation 8.1% Dapagliflozin vs 6.9% Placebo (CI 1.03-1.28) Major hypoglycemic event 0.7% Dapagliflozin vs 1.0% Placebo (CI 0.49-0.95) Diabetic ketoacidosis 0.3% Dapagliflozin vs 0.1% Placebo (CI 1.10-4.30) Genital Infection 0.9% Dapagliflozin vs 0.1% Placebo (CI 4.19-16.68) Acute kidney injury 1.5% Dapagliflozin vs 2.0% Placebo (CI 0.55-0.87) Criticisms Any reason the investigator believes the patient won’t be compliant Aspartate Transaminase (AST) or Alanine Transaminase (ALT) >3x the upper limit of normal or total bilirubin >2.5x the upper limit of normal.Diagnosis of type 1 diabetes mellitus, maturity onset diabetes of the young (MODY), or secondary diabetes mellitus.CrCl 180 or diastolic BP >100 mmHg at randomization.No known cardiovascular disease AND at least 2 factors in addition to type 2 diabetes mellitus: Males ≥ 55 years old and females ≥ 60 years old and Dyslipidemia, hypertension OR tobacco use.Established CV disease (ischemic heart disease, cerebrovascular disease, peripheral arterial disease).High risk for CV event defined as having either established CV disease and/or multiple risk factors:.Diagnosed with Type 2 Diabetes Mellitus.Provision of informed consent prior to any study specific procedures.Primary outcome: MACE (cardiovascular death, myocardial infarction, or ischemic stroke).Setting: conducted in 882 sites in 33 countries.n = 17,160 patients completed run-in phase and underwent randomized.randomized, double-blind, multicenter, placebo-controlled, phase 3b trial.It has shown to reduce risk of chronic kidney disease progression, CV events or both. Consider SGLT-2 inhibitor or GLP-1 receptor agonist in patients with type 2 diabetes and chronic kidney disease.SGLT-2 inhibitors are preferred in patients with athersclerotic CV disease who are at risk of heart failure or if heart failure coexists.In patients with type 2 diabetes and atherosclerotic CV disease, sodium-glucose cotransporter 2 (SGLT-2) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1) are recommended.It was stated that this was not added due to their trail and they had an adaptive design. A second outcome of hospitalization was added due to outside information pointing to a lower hospitalization rate with SGLT-2 inhibitors. There is a possibility of bias being introduced due to the premature permanent drug discontinuation for various reasons including adverse events. The study found that the use of dapagliflozin in patients with cardiovascular risk will result in lower hospitalization with no significant effect on major adverse cardiovascular events. The trial was fairly large involving 17,160 patients at risk for the events resulting in an acceptable sample size 8,852 patients received the treatment and 8,578 patients received the placebo. Patients were also assessed on secondary safety outcomes of renal dysfunction and death from any cause. In this randomized, double-blind, multinational, placebo-controlled, phase 3 trial conducted in 882 cities in 33 countries, patients at risk for atherosclerotic cardiovascular disease were observed for 4-8 weeks on either a placebo or dapagliflozin to assess the primary safety outcome of major adverse cardiovascular events. The cardiovascular profile of dapagliflozin was previously not specified as it relates to safety. Dapagliflozin did result in lower hospitalization rates due to heart failure.ĭapagliflozin is a selective inhibitor of sodium glucose cotransporter-2 (SGLT-2) used in the control of type 2 diabetes. In patients with type 2 diabetes and risk of cardiovascular disease, the use of Dapagliflozin did not significantly reduce the risk of MACE. In patients with type 2 diabetes and at risk for cardiovascular disease, does the use of Dapagliflozin reduce the risk of major adverse cardiovascular events (MACE)?

Declare trial dapagliflozin