FDA Approves Invokana, A Drug To Treat Type 2 Diabetes

The latest tool in mainstream medicine's war on diabetes is a medication developed by Mitsubishi Tanaba Pharmaceticals, licensed in the United States by Janssen Pharmaceuticals. and manufactured by Johnson & Johnson Pharmaceuticals known as Invokana. The generic name of the drug is canafliflozin. Invokana is the first of a new class of diabetes drugs known as sodium-glucose co-transporter 2 (SGLT2) inhibitors.

First Diabetes Drug to Take Advantage of Sodium-Potassium Balance in Cells

Invokana is a drug designed to advantage of the fact that for insulin to transport glucose from the bloodstream into a cell, it has to transport sodium at the same time. For every molecule of sugar that goes into the cell, three ions of sodium have to tag along, while two ions of potassium have to be expelled.

The exchange of sodium and potassium creates a slightly positive charge inside the cell that "pulls in" the slightly negatively charged glucose from the bloodstream.  

Moving sugar out of the bloodstream into most cells in the body, of course, is a good thing, since diabetes is defined as a disease of high blood sugar levels. But moving sugar that has "spilled over" into the urine back into the filtering tubules of the kidneys is not.

Invokana's action is specific to the kidneys, stopping them from responding to the transporter molecule and allowing them simply to flush away excess sugar.

Just How Effective is Invokana?

Clinical trials have shown that taking Invokana lowers hemoglobin A1C (HbA1C) levels by an average of 0.6 to 0.7%, roughly corresponding to a reduction in "average" blood glucose levels of 10-12 mg/dl (about 0.6 mmol/L). This is a better blood glucose reduction than almost any other anti-diabetes drug on the market,

with the exceptions of insulin and metformin, although insulin and metformin produce much more dramatic reductions in average blood sugar levels. And unlike insulin and the older anti-diabetes medications that work by stimulating the pancreas to produce more insulin,

The retail price of Invokana has not been announced, but the wholesale price has been set at $8.77 per tablet, or $263.10 for a one-month supply. Consumers are not likely to have to pay more than $550 per month for the drug.

It turns out, a lot.

Questions Left Unanswered In Clinical Testing May Make Invokana Less than Optimal Choice

The FDA advisory committee that approved Invokana did so without a unanimous vote. In fact, 5 of the 15 experts on the panel recommend against approving Invokana, much as the majority of another FDA panel recommended against approving dapagliflozin, a very similar drug, on safety grounds.

Some members of the panel also expressed concern that the product has no warning label, and it may be particularly dangerous for type 2 diabetics who have kidney disease, which is a large percentage of type 2 diabetics who have had poorly controlled blood sugar levels for 15 years or more.

A Sad History of Failed Diabetes Drugs

The reality of the pharmaceutical market is that new diabetes drugs tend to be rushed to market.

Rezulin was taken off the market three years after it was introduced. The two other diabetes medications in the same class, Actos (pioglitazone) and Avandia (rosiglitazone) have not been pulled from the market despite being implicated as the cause of hundreds of heart attacks, and despite a side effect most diabetics find particularly upsetting: Actos and Avandia transform stem cells that the body makes to create new bone and blood cells into baby fat cells.

In 2006 and 2007, diabetes drug makers introduced a new class of medications known as the incretin drugs. These drugs alter the same the lining of the digestive tract responds to carbohydrate. They also seem to increase the number of insulin-producing beta-cells in the pancreas. A study of the pancreases of diabetics who had died of heart attack or stroke, however, found that 12 out of 14 diabetics who have been taking incretin drugs (such as Onglyza, Trajenta, or Victoza) had changes in their beta-cells that suggested the early stages of pancreatic cancer.

And in the case of Invokana, the increased risk of heart attack and stroke made the headlines, but these are hardly the only potential side effects of the drug.

A Long List of Potential Side Effects

Some of the things that can go wrong, and have gone wrong, in diabetics who use Invokana include:

• Urinary tract infections (UTIs). Invokana increases the amount of sugar that stays in urine, and the sugar feeds bacteria. In the clinical trial of the drug, 1 in 10 women who took developed a yeast infection, and 1 in 20 people who took developed a UTI.
• Dangerously high potassium levels. Invokana changes the chemistry of the kidneys so that they are less likely to remove potassium from the bloodstream. Since many diabetics also take ACE-inhibitor or ACE-receptor blocker medications that make the kidneys less likely to remove potassium from the bloodstream, toxic levels of potassium can build up. Older people, over 75, are especially susceptible to this complication.

 In some cases, taking metformin can lower HbA1C as much as 1.4%. That's roughly equivalent to a consistent lowering of blood sugar levels by 21 mg/dl (1.4 mmol/L). When diabetics in the clinical trial took both metformin and Invokana, however, the benefit of metformin was lowered to about 0.8% HbA1C, roughly equivalent to lowering average blood sugar levels by 12 mg/dl (0.8 mmol/L).

The best that can be said for Invokana probably is that it is not ready for prime time. Ask your doctor to consider delaying a prescription for Invokana until its side effects are well known. Invokana appears  not to do anything metformin can't do, and it may cause serious harm.