Canagliflozin review – safety and efficacy profile in patients with T2DM

Haroon Jakher,1 Tara I Chang,2 Marilyn Tan,3 Kenneth W Mahaffey4 1Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA; 2Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA; 3Division of Endocrinology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA; 4Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA Abstract: Canagliflozin is a sodium glucose-cotransporter (SGLT) receptor inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). This article reviews the mechanism of action of SGLT-2 receptor inhibitors and the efficacy of canagliflozin as an antidiabetic agent, its cardiovascular and renal benefits, and safety profile. During the development of canagliflozin, Phase II trials showed an improvement in cardiac and renal biomarkers such as blood pressure, body weight, and albuminuria. The large CANVAS program showed that canagliflozin reduced the composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The CANVAS program also showed a possible benefit of canagliflozin on a renal composite of sustained 40% reduction in estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes. The safety profile of canagliflozin has been well characterized, and known side effects such as mycotic genital infections were confirmed in CANVAS. However, an increased risk of amputations was observed in CANVAS that requires further study. Overall, canagliflozin is an effective antidiabetic medication with cardiovascular and likely renal benefits, and with a generally well-tolerated safety profile. Results from the CREDENCE trial will further evaluate the safety and potential renal benefits of canagliflozin in patients with established diabetic nephropathy. Keywords: canagliflozin, sodium glucose-cotransporter, diabetes, CANVAS, Invokana®, renal, cardia