Canagliflozin (Invokana™) is an orally administered sodium-glucose co-transporter-2 (SGLT2) inhibitor used in the treatment of patients with type 2 diabetes. By inhibiting the transporter protein SGLT2 in the kidneys, canagliflozin reduces renal glucose reabsorption, thereby increasing urinary glucose excretion and reducing blood glucose levels. Several randomized placebo- or active comparator-controlled trials of 26–52 weeks’ duration (plus extension phases) have shown that canagliflozin improves glycaemic control when used as monotherapy or as add-on therapy to metformin and/or other antihyperglycaemic agents, including insulin, in patients with type 2 diabetes. In addition to achieving reductions from baseline in glycosylated haemoglobin, canagliflozin also showed beneficial effects for other endpoints including reductions from baseline in fasting plasma glucose levels and bodyweight. Canagliflozin has a low risk of hypoglycaemia and was generally well tolerated in clinical trials. The most frequently reported adverse events with canagliflozin are female genital mycotic infections, urinary tract infections and increased urination. The pharmacodynamic response to canagliflozin declines with increasing severity of renal impairment, and prescribing information should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Canagliflozin has modest effects on the serum lipid profile, some beneficial (increased high-density lipoprotein cholesterol and decreased triglycerides) and others not (increased low-density lipoprotein cholesterol). Most patients treated with canagliflozin also have a modest reduction in blood pressure. The overall effect of canagliflozin on the risk of cardiovascular disease is unknown and will be evaluated in the ongoing CANVAS trial; preliminary cardiovascular safety data suggest no increased risk. Thus, with its unique mechanism of action that is independent of insulin secretion and action, canagliflozin is a useful addition to the therapeutic options available for the management of type 2 diabetes, particularly by providing complementary treatment when used as add-on therapy.
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The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes based on any comments received were made by the author on the basis of scientific and editorial merit. Greg Plosker is a salaried employee of Adis/Springer.
The manuscript was reviewed by: D.S.H. Bell, Southside Endocrinology, University of Alabama, Birmingham, AL, USA; G. Dimitriadis, 2nd Department of Internal Medicine, Research Institute & Diabetes Center, Athens University Medical School and Attikon University Hospital, Athens, Greece; J.G. Eriksson, Department of General Practice & Primary Health Care, Finland and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland; D.T. Eurich, School of Public Health, University of Alberta, Edmonton, AB, Canada; A.J. Scheen, Division of Diabetes, Nutrition and Metabolic Disorders and Division of Clinical Pharmacology, Department of Medicine, CHU, University of Liège, Liège, Belgium.
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Plosker, G.L. Canagliflozin: A Review of Its Use in Patients with Type 2 Diabetes Mellitus. Drugs 74, 807–824 (2014). https://doi.org/10.1007/s40265-014-0225-5
- Glycaemic Control
- SGLT2 Inhibitor