Canagliflozin and Cardiovascular disease- results of the CANVAS trial

Abstract

Canagliflozin is a new novel oral antidiabetic agent belonging to the class of sodium–glucose co-transporter 2 (SGLT2) inhibitors, inhibiting glucose reabsorption in the proximal tubule, leading to increased urinary glucose excretion and subsequently to reduction in plasma glucose concentration, in individuals with hyperglycemia. Before the approval of canagliflozin by the Food and Drug Administration (FDA) in 2013, a pair-wise meta-analyses of trials involving canagliflozin did not differ from control in terms of all-cause mortality, cardiovascular death, myocardial infarction, and stroke. However, no large, randomized-controlled trials were available for comparison until the results of the CANVAS (Canagliflozin Cardiovascular Assessment Study) trial were published. The CANVAS Trial was designed to assess the cardiovascular safety and efficacy of canagliflozin. Recently, results of the completed CANVAS Trial were released which showed patients with type 2 diabetes and established cardiovascular disease or at high risk for cardiovascular events who were treated with canagliflozin had significantly lower rates of the primary cardiovascular outcome than patients assigned to placebo. All three components of the primary outcome – death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke – showed point estimates of effect that suggested benefit .These results may represent a significant additional therapeutic tool in the clinical prevention and management of cardiovascular mortality and morbidity. However, data on the long-term efficacy on the use of Canagliflozin is still incomplete and their use in patients with type 2 diabetes should be carefully considered.

Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

“…A new group of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is), has recently been shown to significantly improve the prognosis in high-risk cardiovascular (CV) patients with type 2 diabetes. The CV outcomes of SGLT2is (empagliflozin, canagliflozin and dapagliflozin) have been evaluated in, among others, three randomised clinical trials: Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), Canagliflozin Cardiovascular Assessment Study (CANVAS) and Dapagliflizin Effect on Cardiovascular Events Thrombosis in Myocardial Infarction 58 (DECLARE-TIMI 58) [1][2][3][4][5][6][7][8][9][10]. The first and thus groundbreaking EMPA-REG OUTCOME study showed that the use of empagliflozin in patients with type 2 diabetes and a high CV risk reduced CV mortality by 38%, without significantly reducing the number of non-fatal myocardial infarctions and strokes [11,12].…”

SGLT-2 Inhibitors in Cancer Treatment—Mechanisms of Action and Emerging New Perspectives

“…Previous trials have confirmed beneficial clinical effects of using SGLT-2 inhibitors in cardiovascular diseases [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Their nephroprotective effect has also been confirmed both in patients with and without diabetes [ 21 , 22 ].…”

“…Their nephroprotective effect has also been confirmed both in patients with and without diabetes [ 21 , 22 ]. There have been many randomised clinical trials to assess the cardiovascular outcomes of SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin), including the Canagliflozin Cardiovascular Assessment Study (CANVAS), the Dapagliflozin Effect on Cardiovascular Events Thrombosis in Myocardial Infarction 58 (DECLARE—TIMI 58) and the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 23 , 24 ]. These clinical trials have revealed that when SGLT-2 inhibitors were administered to patients there was a significant reduction in CV mortality.…”

Changing the Concept: From the Traditional Glucose-centric to the New Cardiorenal-metabolic Approach for the Treatment of Type 2 Diabetes

“…(defined as HbA1 ≥7.0% and ≤10.5%), CVD and CV risk factors. 62 A total of 10,142 patients were enrolled and randomized to either the canagliflozin-treated group (n=5,795) or a placebo group (n=4,347). 60,61 Mean follow-up was 188 weeks.…”

“…Moreover, canagliflozin showed a 33% reduction in hospitalization due to HF compared with the placebo. 60,62,63 Remarkably, canagliflozin was reported to be more efficacious in individuals with a history of HF, body mass index ≥30 kg/m 2 and HbA1c ≥8%. Canagliflozin proved to have a potent renoprotective profile by reducing the presence or development of albuminuria incidents by 27% and 20%, respectively.…”