Investigational and emerging treatments are attempting to achieve certain outcomes in order to have a “place at the table” in the management of type 2 diabetes. Some of these desired characteristics include minimal to no risk of hypoglycemia and weight maintenance or loss with an effective A1c reduction.
On March 29, a new drug was approved for the management of type 2 diabetes. Canagliflozin, also known as INVOKANA, is the “first FDA-approved agent” in a new therapeutic class known as the sodium glucose co-transporter 2 (SGLT2) inhibitors. In healthy individuals, approximately 90 percent of the filtered glucose is reabsorbed by SGLT2 in the proximal renal tubule. The kidney desires to excrete excessive, filtered glucose in order to restore normal levels of glucose in the blood. In a patient with type 2 diabetes, the kidney is dysfunctional and responds to hyperglycemia through glucose reabsorption. (Defronzo RA, Diabetes 2009)
Canagliflozin is a selective SGLT2 inhibitor, which will decrease blood glucose levels secondary to the process of glucosuria in which glucose is excreted in the urine. Since its mechanism is independent of insulin and does not affect circulation, it has a low risk of hypoglycemia. Canagliflozin promotes glucose excretion through the kidney. As a result, some patients might experience minimal weight loss. Due to its selectivity of SGLT2, canagliflozin has no affinity for SGLT1, which is located in the small intestines. Therefore, adverse, gastrointestinal effects should be minimized with canagliflozin. Lastly, canagliflozin has been associated with having a diuretic quality, and thus avoids fluid retention seen with other drugs like rosiglitazone or pioglitazone.
Canagliflozin has been studied in 9 clinical trials among 10,285 patients with type 2 diabetes. As the sole therapy, 100 and 300 mg daily doses resulted in 0.91 and 1.16 percent A1c reduction. Canagliflozin has been an effective adjunctive agent with other antihyperglycemic agents, such as metformin and insulin.
Canagliflozin offers several advantages:
1. Patient-friendly form (oral, once-daily)
2. Novel (yet simple) process to decrease blood glucose levels
3. Adequate glycemic effect as a single or combination therapy
4. Additional benefits:
a. Weight loss of five to seven pounds
b. Blood pressure reduction of 3.7 to 5.4 mm Hg
5. Minimal risk of hypoglycemia
Canagliflozin can be considered a new addition to the spectrum of diabetes management. This alternative provides clinicians another effective agent, but with several benefits as listed above. However, clinicians should also be aware of the two most common adverse events in clinical trials – vulvovaginal candidiasis and urinary tract infections. In addition, all new oral antihyperglycemic agents must be investigated in further clinical trials regarding cardiovascular mortality. Lastly, clinicians will want to know the evidence of canagliflozin in special populations, such as geriatric, renal or hepatic-impaired patients.
To me, this agent provides an innovative way of improving blood glucose in patients with diabetes. However, I do not anticipate it replacing first-line agents, such as metformin, due to the lack of long-term data and evidence. For canagliflozin, a big factor will be cost, which is estimated to be $8.77 per day. With this new, FDA-approved drug, I would reinforce that diabetes management should be individualized and take into consideration the drug’s effectiveness, the patient’s preference and tolerance for the drug, and cost.