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The FDA has given a thumbs-up to a first-in-class medication for type 2 diabetes, but with a stipulation that the drugmaker conducts multiple postmarketing studies.
The agency approved the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin (Invokana) in conjunction with diet and exercise to improve glycemic control in adults with type 2 diabetes, according to an announcement made Friday.
The drug is the only compound approved for diabetes that does not have an effect on insulin. Instead, it blocks the reabsorption of glucose by the kidney, increasing glucose excretion directly into the urine.
However, drugmaker Janssen Pharmaceuticals, a Johnson & Johnson company, will have to conduct five postmarketing studies:
- Cardiovascular outcomes trial
- Bone safety study
- Two pediatric trials
- Monitoring program for malignancies, serious cases of pancreatitis, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, and adverse pregnancy outcomes
The need for greater cardiovascular outcome monitoring was emphasized by panelists at the drug's advisory committee meeting in January. Some called for a larger study before the drug hit the market because the company's cardiovascular study, the CANVAS trial, showed a nonsignificant increase in major adverse cardiovascular events in the first 30 days of starting on the agent.
Cardiovascular safety has become a major issue for diabetes drugs since studies revealed an increased risk for heart failure with both pioglitazone (Actos) and rosiglitazone (Avandia).
Approval was based on nine clinical trials involving more than 10,285 patients with type 2 diabetes. The trials showed significant improvement in glycated hemoglobin (HbA1c) levels and fasting plasma glucose with the drug compared with placebo, as well as noninferiority to other common diabetes drugs glimepiride (Amaryl) and sitagliptin (Januvia).
The agency warned, however, that canagliflozin is not for use in patients with type 1 diabetes, and is contraindicated in patients who have increased ketones in their blood or urine.
Patients are also ineligible for the drug if they have severe renal impairment, end-stage renal disease (ESRD), or are currently on dialysis.
Common side effects include vaginal yeast infections and urinary tract infections, due to the increased sugar in the urine.
The FDA also cautioned that because the drug is associated with a diuretic effect, it could cause a reduction in intravascular volume leading to orthostatic or postural hypotension. In turn, patients may experience dizziness or fainting, most commonly in the first 3 months starting therapy.
Another SGLT2 inhibitor, dapagliflozin, was rejected by the FDA last year over concerns about breast and bladder cancer risks, which were not seen with canagliflozin.