Canaglifozin: friend or foe?
Type 2 diabetes is the third most frequent disease affecting the population worldwide. Per data reported by the world health organization 422 million people have been diagnosed with this disease, meaning that 1 in every 11 people have it. Diabetes presents itself with altered blood glucose levels resulting in health complications secondary to sickness progression; furthermore this sickness is associated with important morbidity and mortality mainly due to the fact that patients have a 50% increased risk of developing cardiovascular disease. 
Because of the high prevalence and health repercussions related to the disease, control and prevention of associated sickness complications has become one of the main goals of family physicians, internists and endocrinologists. Thus, medications that not only lower blood glucose have been developed, (oral hypoglycemics and human insulins) but also prevent kidney damage, cardiovascular and infectious diseases as well.
One of the newer class of drugs for the management of type 2 Diabetes Mellitus (DM 2) is canaglifozin, a sodium-glucose transport protein 2 inhibitor (SGLT2) that inhibits glucose reabsorption in proximal convoluted tubules in the kidneys, resulting in an increased glucose excretion thus a lower blood glucose concentration. 
Canaglifozin has been approved by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the National Institute of Food and Drug Surveillance (INVIMA by its Spanish acronym) as a second or third line of treatment in patients with DM 2. Some of the positive outcomes seen with canaglifozin treatment are reduction in glycated hemoglobin, fasting glucose levels, weight loss and blood pressure control outcomes that are not only important in DM 2 control but can also reduce cardiovascular risk without the dreaded hypoglycemia that be produced with other drugs. 
Vascular peripheral disease is one of the main complications seen in patients with DM 2, progression of the disease and can ultimately lead to the amputation of a limb with important economic and social repercussions in everyday life. Diabetes medication seek to prevent such complications, but recent studies for cardiovascular (CANVAS) and renal evaluation (CANVAS-R) have found that patients taking canaglifozin showed and two-fold increased risk of amputation in lower limbs vs patients taking placebo. Patients with ulcers seem to be more at risk, and both studies are still ongoing and definite results have not been published. 
In the light of these events, both the FDA and EMA have issued warnings related to canaglifozin treatment, advising patients to report existing ulcers and lower limb wounds to their doctors, as well as recommending health care professionals to perform routine thorough physical examinations alongside a medical treatment aimed at preventing risk factors for vascular peripheral disease. 
Finally, when selecting a glucose lowering treatment patient´s individual comorbidities, risks and needs should be taken into consideration; and as canaglifozine is a new drug it should be noted that safety trials are still inconclusive and prescription should not be taken lightly. 
Vallejos Alvaro **. Botto Sarai* y Martinez Viviana*
** Physician, Health Science PhD candidate, Magister in Pharmacology; Magister in Education for Health Professionals, advanced studies in Epidemiology
-  Organización Mundial de la Salud (2016). Informe mundial sobre la diabetes. Recuperado de: http://www.who.int/diabetes/global-report/en/
-  Karagiannis, T., Bekiari, E., Tsapas, A. Canagliflozin in the treatment of ype 2 diabetes: an evidence-based review of its place in therapy. Core Evidence 2017:12 1–10
-  Food and Drug Administration (16/05/2017). Canagliflozin (Invokana, Invokamet): Drug Safety Communication – Increased Risk of Leg and Foot Amputations. Recuperado de: https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm558605.htm
-  European Medicines Agency (24/02/2017). SGLT2 inhibitors: information on potential risk of toe amputation to be included in prescribing information. Recuperado de: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2017/02/WC500222191.pdf
-  Bruce Neal et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS)—A randomized placebo-controlled trial. Am Heart J 2013;166:217-223.e11.
-  Bruce Neal et al. Rationale, design and baseline characteristics of the Canagliflozin cardiovascular Assessment Study–Renal (CANVAS-R): A randomized, placebo-controlled trial. Diabetes Obes Metab 2017; 19(3):387–393
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