Available online on www.ijtpr.com International Journal of Toxicological and Pharmacological Research 2015; 7(2); 105-107 ISSN: 0975-5160 Research Article *Author for Correspondence Canagliflozin: A First-in-Class Medication for the Treatment of Type 2 Diabetes Mellitus Dylan Hosein 1 , Akram Ahmad 2 , Muhammad Umair Khan 2 and *Sameer Dhingra 1 1 School of Pharmacy, The University of the West Indies, St. Augustine, Trinidad and Tobago 2 Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia Available Online:15 th March, 2015 ABSTRACT Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It results from defects in insulin secretion, insulin sensitivity, or both. Chronic microvascular, macrovascular, and neuropathic complications may ensue.Despite the large amount of treatment options available, Diabetes Mellitus is not well managed. Canagliflozin, a recently approved first-in-class anti-diabetic medication, employs a novel mechanism of action which is not dependent upon insulin release or improving insulin sensitivity. It is a sodium glucose co-transporter 2 (SGLT-2) inhibitor, developed to treat hyperglycemia in Type 2 Diabetes Mellitus patients. This causes more glucose to be removed from the urine, thereby lowering blood sugar levels. Canagliflozin was reported to improve glycemic control, reduce body weight and systolic BP, and was generally well tolerated in older subjects with T2DM who were on background therapy with a variety of blood glucose-lowering agents. Keywords: canagliglozin, diabetes mellitus INTRODUCTION Within the last three decades, the prevalence of type-2 diabetes in the U.S. has more than tripled, accounting for 90% to 95% of the diagnosed cases 1,2 . It is projected that one in three American adults will have diabetes in 2050 if this trend continues 3 . The incidence of the disease is increased in obese patients, minority populations, and the elderly. Diabetes, which is characterized by chronic long- term hyperglycemia, is associated with serious complications, including blindness, kidney failure, amputations, and death 3 . Despite current available therapies, less than 50% of patients in the U.S. are achieving desired levels of glycosylated haemoglobin (HbA1c), blood pressure, and low-density lipoprotein-cholesterol (HDL-C) levels, as recommended by the American Diabetes Association (ADA) 4 . Recent recommendations from the ADA and the European Association for the Study of Diabetes (EASD), along with the American Association of Clinical Endocrinologists (AACE), advise a patient-centred approach to management 4,5 . Preferred medications are those that carry a low risk of hypoglycemia, minimize the risk of weight gain, are easy to administer, are cost- effective, and are safe to use 5 . In March 2013, the USFDA approved canagliflozin as an adjunct to diet and exercise for adults with type-2 diabetes mellitus. This is the first oral agent in a novel class of diabetes drugs known as sodium–glucose co-transporter-2 (SGLT-2) inhibitors 6 . Current research has focused on the role of the kidney in glucose homeostasis and has identified the role of SGLT-2 in mediating the re- absorption of filtered glucose in the proximal tubule 6,7 . The inhibition of SGLT-2 provides a novel mechanism to lower elevated plasma glucose levels in diabetic patients 7,8 . INDICATIONS Canagliflozin is approved for adults with type-2 diabetes mellitus who require improved glycemic control in addition to diet and exercise. This drug has not been studied for and is not recommend for patients with type-1 diabetes mellitus or diabetic ketoacidosis 9 . Recommended Dosage and Pre-Medication The recommended starting dose of Canagliflozin is 100 mg once daily, taken before the first meal of the day. Assessment of renal function is recommended prior to initiation of Canagliflozin therapy and periodically thereafter 9 . In patients tolerating Canagliflozin 100 mg once daily who have an estimated Glomerular Filtration Rate of 60 mL/min/1.73 m 2 or greater and require additional glycemic control, the dose can be increased to 300 mg once daily. Canagliflozin should be discontinued when eGFR is persistently less than 45 mL/min/1.73 sq.m 10 . CLINICAL PHARMACOLOGY Mechanism of Action Canagliflozin is used along with diet and exercise, and sometimes with other medications, to lower blood sugar levels in patients with type 2 diabetes. Canagliflozin is in a class of medications called sodium-glucose co- transporter 2 (SGLT2) inhibitors. It lowers blood sugar by causing the kidneys to get rid of more glucose in the urine.