The SGLT2 Inhibitors Are Coming!   (January 19, 2013)

Update March 29, 2013: Canaglifozin (brand name Invokana) has been approved by the FDA.
Update January 8, 2014: Dapaglifozin (brand name Farxiga) has been approved by the FDA.

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Another class of diabetes medications is working its way through the regulatory requirements that every medication manufacturer must face to receive approval to sell a prescription drug. The new class is called "sodium-glucose co-transporter 2 inhibitors" or "SGLT-2 inhibitors" – which work to control glucose levels in patients with type 2 diabetes by a novel mechanism: they cause the loss of extra glucose into the urine, which in turn allows both the blood glucose levels and the A1C to decrease. And, as I’ve discussed previously, it would seem that all the SGLT2 inhibitors will be associated with a side effect of increased risk of genitourinary infections. 

There’s a race between two drug makers to be the first to get approval to sell their SGLT2 inhibitor in the lucrative US market. There’s usually perceived to be a huge financial plus to being the first-to-market, so both companies have been pushing hard.

In Europe, one SGLT has already won the race: FORXIGA™ (dapagliflozin) (developed by Bristol-Myers Squibb and AstraZeneca) was approved for the treatment of type 2 diabetes in late 2012. 

Interestingly, when making this announcement, these manufacturers totally ignored the fact that the US FDA has requested additional clinical data before considering whether to approve dapagliflozin. The huge surprise in the safety data that was presented to the FDA from the dapagliflozin clinical trials was that breast and bladder cancers were found at higher rates in patients taking dapagliflozin. Oops; definitely not a good thing.

BTW, there’s a company-sponsored website, http://www.forxiga.com/, which has the usual mixture of information about how wonderful the drug is. But you can’t read the information unless you declare that you are an EU healthcare professional. Oh well. That website doesn't discuss the cancer risk except to quote from the labeling document (called the Summary of Product Characteristics or SmPC) that there was a "numerical imbalance of breast, bladder and prostate tumours [which] must be considered with caution, [and which]... will be further investigated in post-authorisation studies."

The other SGLT2 inhibitor that’s in the race to be first in the US, and which now seems likely to be the first across the finish line, is called canagliflozin (it’s proposed brand name is INVOKANA™).  This drug was just reviewed earlier this month by the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee (AKA the "adcom"). The adcom voted 10-5 to recommend approval for canagliflozin to treat type 2 diabetes in adults. 

Adcom members were reported to have concerns about risks of heart disease and stroke, and about the use and safety of this drug in people with kidney disease. But, unlike dapagliflozin, there doesn’t seem to be a signal of increased risk of cancer with canagliflozin. (The slides presented by the FDA and the  manufacturer are on the FDA website if you want to see the details.)

Since the FDA usually follows the recommendations of their adcoms, it would seem likely that canagliflozin may win the race to be the first SGLT2 inhibitor on the market in the US. Which will increase the number of classes of drugs available to treat diabetes to an even dozen.