FDA has approved canagliflozin (Invokana—Janssen Pharmaceuticals) for the treatment of adults with type 2 diabetes. This novel agent is the first diabetes treatment in a new class of drugs known as sodium–glucose cotransporter 2 (SGLT2) inhibitors.

Canagliflozin is the only oral, once-daily medication available in the United States to improve glycemic control in adults with diabetes when used in conjunction with diet and exercise. The agent carries several safety warnings about infection, however, and FDA is requiring five postmarketing studies for canagliflozin.

Novel mechanism of action

SGLT2 inhibitors offer patients with type 2 diabetes a unique insulin-independent approach for managing hyperglycemia without experiencing hypoglycemia. SGLT2 is primarily responsible for the reabsorption of filtered glucose in the kidney. As an inhibitor of SGLT2, canagliflozin lowers the reabsorption of filtered glucose and the renal threshold for glucose, which increases the excretion of urinary glucose.

Canagliflozin’s approval was based on nine clinical trials that included more than 10,285 patients with type 2 diabetes. Results from the trials showed that the 100-mg and the 300-mg doses of canagliflozin improved glycemic control and were associated with reductions in body weight and blood pressure. In addition, the agent was evaluated as a stand-alone therapy and in combination with other drugs for treating patients with type 2 diabetes, including pioglitazone, metformin, sulfonylurea, and insulin.

The most common adverse effects caused by canagliflozin included genital mycotic infection, urinary tract infection, and increased urination.

More studies

FDA is requiring five postmarketing studies for canagliflozin: a cardiovascular outcomes trial; a bone safety study; two pediatric studies under the Pediatric Research Equity Act, including a pharmacokinetic and pharmacodynamic study and a safety and efficacy study; and an enhanced pharmacovigilance program to monitor for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, liver abnormalities, photosensitivity reactions, and adverse pregnancy outcomes.

In addition to canagliflozin, a handful of other SGLT2 inhibitors are in the pipeline. In January 2012, the SGLT2 inhibitor dapagliflozin (Forxiga—AstraZeneca, Bristol-Myers Squibb), was not approved by FDA because of breast and bladder cancer concerns; however, it was approved in Europe a few months later. In March 2013, another SGLT2 inhibitor, empagliflozin (Boehringer Ingelheim—Eli Lilly), was submitted to FDA for approval.

Canagliflozin (Invokana)

Manufacturer: Janssen Pharmaceuticals

Drug class: Sodium–glucose cotransporter 2 (SGLT2) inhibitor

Dosage: 100 mg once daily, taken before the first meal of the day

Dose may be increased to 300 mg once daily in patients who tolerate the 100-mg dose and have an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 or greater and require additional glycemic control.

In patients who have an eGFR of 45 to less than 60 mL/min/1.73 m2, the dosage is limited to 100 mg once daily.

Of note: Warnings and precautions for canagliflozin include hypotension, impairment in renal function, hyperkalemia, hypoglycemia with concomitant use with insulin and insulin secretagogues, and genital mycotic infections.

Canagliflozin is not recommended for treating patients with type 1 diabetes or patients with type 2 diabetes who have increased ketones in their blood or urine, severe renal impairment or end-stage renal disease, or those receiving dialysis.

Patient counseling

Give patients the Medication Guide and instruct them to read it; also instruct patients to drink enough fluids when initiating the drug. Because the agent is associated with a diuretic effect, it may cause a reduction in intravascular volume leading to orthostatic or postural hypotension. As a result, patients may experience dizziness or fainting, especially in the first 3 months of therapy. Encourage patients to stay on their prescribed diet and exercise program while taking canagliflozin. Inform patients that genital mycotic infection, urinary tract infection, and increased urination are the most common adverse effects caused by canagliflozin.