Invokana, First Drug in a New, Dangerous Class of Diabetes Drugs
The FDA just gave its approval to the first drug in a new class of diabetes drugs, Johnson & Johnson's canagliflozin, which will be marketed in the U.S. as Invokana.
New York Times: FDA Approves a New Diabetes Drug From J.&J. (May require subscription)
Reuters: U.S. FDA approves Johnson & Johnson diabetes drug, canagliflozin
This class of drugs, the sodium-glucose co-transporter-2 (SGLT2) inhibitors, lowers blood sugar by blocking reabsorption of glucose by the kidney and increasing its excretion in urine. The manufacturer also claims that it causes weight loss--always a potent selling point for a diabetes drug.
As is the case with all new diabetes drugs, now that the drug is approved, drug company flacks will start saturation bombing family physicians with materials that make it sound like they should put every patient with Type 2 on this wonderful, new drug, which is priced at $8.77 a pill or $263.10 for a monthly supply.
The committee of "experts" who reviewed this drug were ambivalent about it because the company's own, [most likely, statistically manipulated], clinical study of patients at especially high risk of cardiovascular disease showed that within the first 30 days, 13 patients taking canagliflozin suffered a major cardiovascular event [mainly strokes and some heart attacks] compared with just one patient taking a placebo. After that, the imbalance was reversed, though the drug then caused a slight increase in LDL cholesterol.
However, as the New York Times report notes, " F.D.A. spokeswoman said Friday that the significance of those findings was unclear, and the label of the drug includes no warnings about heart attacks or strokes."
That means that busy family physicians who are conscientious enough to review the FDA Prescribing Information will have no idea that they may exposing some of their previously stable patients with Type 2 Diabetes to life-altering strokes and heart attacks that will either kill them or ruin their quality of life.
One third of the experts in the FDA committee who reviewed the research J&J provided about Invokana advised against approving this drug (5 out of 15). They also expressed concern that this drug might be more dangerous for people with kidney disease--which of course, describes a lot of people with Type 2 Diabetes who have followed conventional medical advice.
A very similar drug that operates on the same pathways, dapagliflozin, was rejected by the FDA on safety grounds, which make it all the more important to worry about the safety of this one.
Johnson & Johnson's current management has shown itself criminally unconcerned with the fate of those who buy its most toxic products, as was demonstrated by the fact that the company continued to market their
metal-on-metal replacement joints long after people inside the company knew that a high number of them were failing within a very few years after surgical implantation, exposing users to the risks of more major surgery and the possibility of joint deterioration that could permanently limit mobility and lead to life long pain and disability. (Details HERE.) With this kind of corporate culture, it is not impossible that J&J insiders might have tweaked the studies used to approve its drug to make them look better than those that led to the rejection of dapagliflozin.
We have learned from the history of the Incretin drugs that when members of a class can't be approved for a long time due to disturbing findings in approval testing, the members of the class that are approved often turn out to have the same effects when given to more patients.
But you can be sure that now that this money-making new drug is officially on the market, J&J will do all it can to keep the public from learning about the true toll it exerts on those who take it.
And of course, as we have now learned from every new expensive diabetes drug released in the past 20 years, the rest of the side effects of this new class of drugs won't begin to become evident until millions of prescriptions have been sold and hundreds of thousands of people suffered whatever else it is that it does to the body, because no approval testing exposes people to a new drug long enough for those effects to become clear. (And many of the effects would require microscopic studies of the tissues of people taking the drugs which are never required for approval.)
Other Side Effects
Unmentioned in any of the news stories about this new drug is the fact, mentioned in Invokana's Prescribing Information, that it causes serious yeast infections in women and uncircumcised men. This makes sense since sugary urine promotes the over-growth of yeast. One in ten of those who took the drug experienced this side effect. One in twenty who took it experienced urinary tract infections.
Decreased Kidney Function
The Prescribing Information states: "INVOKANA increases serum creatinine and decreases eGFR [glomerular filtration rate.]" It also raises the risk of dangerous low blood pressure and hyperalkemia (high potassium levels) especially in people taking blood pressure medication. (Hyperalkemia can lead to heart rhythm abnormalities. Older people, particularly those over 75 are those most likely to have the most severe kidney-based reactions to the drug.
Effect on Blood Sugar
A low dose of the drug (100 mg) lowered A1c on average .79% (i.e. from 8.0% to 7.21%. The high dose (300 mg) lowered A1c, on average .94%. In contrast, the impact of plain metformin on blood sugar, according to the Glucophage prescribing information (available HERE) is to lower blood sugar 1.4% over 29 weeks. The combination of metformin and Invokana did not make any change in the drop in A1c which remained, on average, the same as it would be with Invokana alone and lower than could be achieved with optimal metformin dosing.
On average, the low dose lowered fasting blood sugar from 173 mg/dl to 155 mg/dl--a level high enough to ensure the development of all the classic diabetic complications. The high dose lowered fasting blood sugar from an average of 173 mg/dl to 138 mg/dl. I
Very significantly, the Prescribing Information does NOT report the effect of this drug on post-meal blood sugars when taken alone. It only reports its effect on post-meal blood sugars when taken with metformin, where it lowers blood sugar by the same amount that metformin alone would lower it. In short, Invokana does not appear to have any significant effect on post-meal blood sugars, and none, overall that couldn't be achieved by taking the cheap generic, metformin, alone.
Even when Invokana was combined with metformin, the combined impact on post-meal blood sugars was unimpressive. The average blood sugar of the untreated people in this study two hours after eating was between 258 mg/dl and 262 mg/dl--a level guaranteed to produce heart disease and other classic diabetic complications. When Invokana was taken along with metformin, their average 2 hour post-meal blood sugar was still 205 mg/dl to 210 mg/dl, a level still high enough to cause heart disease and all the classic diabetic complications.
This makes it clear Invokana offers no significant benefit to people with Type 2 diabetes. We know from several research studies that post-meal blood sugars over 155 mg/dl promote the development of heart disease. (Details HERE)
You can find everything that J&J will let the public know about Invokana here: Invokana Prescribing Information
Say "No" to Brand New Diabetes Drugs!
If your doctor tries to put you on this drug, say no. Wait ten years, and search the literature then to see what scientists have found out about its real effects on patients before you try it.
If you can't control your blood sugar using standard therapies the safest approach is this:
1. Try the dietary strategy described on this page: How to Lower Your Blood Sugar
2. If that doesn't lower your blood sugar to a healthy level, ask your doctor about starting metformin ER. Make sure you end up with a clinically effective dose which for most people is at least 1500 mg a day. The ER form is kinder to the stomach.
3. If you don't respond to metformin, ask your doctor to prescribe long-acting insulin, which should lower your fasting blood sugar. Read up on how to set the dose so that it is most effective.
4. If that isn't enough, ask your doctor to prescribe fast acting insulin to cover the carbs in your meals. Read up to learn how to set the dose, as most family doctors don't have the resources to give Type 2s the proper training in using this kind of insulin. (Don't use mixtures of fast and slow insulin (70/30 mixes) as they almost always make it extremely hard to get good control of blood sugar.)
These are the safe, long-tested strategies that provides the best reward for the smallest amount of risk in people with Type 2 diabetes.