Canagliflozin: New drug for management of type 2 diabetes mellitus

The U.S. Food and Drug Administration approved Invokana (canagliflozin) tablets, to be used with diet and exercise, to improve glycemic control in adults with type 2 diabetes on 30^th March, 2013.¹

Canagliflozin is a sodium-glucose co-transporter2 (SGLT2) inhibitor, a new group of oral hypoglycemic drugs.

Invokana works by blocking the reabsorption of glucose by the kidney, increasing glucose excretion, and lowering blood glucose levels in diabetics who have elevated blood glucose levels. Its safety and effectiveness were evaluated in nine clinical trials involving over 10,285 patients with type 2 diabetes. The trials showed improvement in hemoglobin A1c levels and fasting plasma glucose levels.

Invokana has been studied as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylurea, pioglitazone, and insulin.

Invokana should not be used to treat people with type 1 diabetes; patients having diabetic ketoacidosis; severe renal impairment, end stage renal disease, or in patients on dialysis.

Most common side effects of Invokana are vulvovaginal candidiasis and urinary tract infection. As Invokana is associated with a diuretic effect, it can cause a reduction in intravascular volume leading to orthostatic or postural hypotension. This may result in symptoms such as dizziness or fainting, and is most common in the first three months of therapy.

SGLT2 inhibitors:²

Glucose is reabsorbed from the proximal tubule of kidneys via family of membrane proteins (or transporters) called SGLTs. Approximately 180 g of glucose is filtered daily in a healthy adult and most of this is reabsorbed by SGLTs, with, 1% being excreted in the urine. Although there are several dif­ferent types of SGLTs, the two most studied are SGLT1 and SGLT2. The latter is responsible for reabsorption of over 90% of the glucose filtered while SGLT1, located in the distal segments, absorbs the remainder. SGLT2 inhibitors block the reabsorption of filtered glucose leading to glycosuria and improvement in glycemic control. These are also associated with a potential for weight loss.

A rare genetic condition, familial renal glucosuria, has served as a model for SGLT2 inhibition. In this dis­order, due to a mutation of SLCA2 gene there is impaired functioning of SGLT2, secondary to mutation of the SLCA2 gene, leading to daily urinary excretion of up to 100 g of glucose. Such patients are generally asymptomatic.

Inhibition of glucose uptake by the kidneys appears to be a new, unique, and promising insulin-independent approach to the treatment of type 2 diabetes.

References:

1.     US FDA. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345848.htm

2.     Kim Y, Babu AR. Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 2012;5:313-27.