March 31, 2013

FDA Approves a Highly Questionable New Diabetes Drug, Invokana

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.

They shouldn't.

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

Yeast Infections

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. However, when Invokana was combined with metformin, the combination only lowered A1c .79% for the low dose and .94% for the high dose--no different than when Invokana was taken alone and less than what is achieved with a proper amount of cheap generic metformin.

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.

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 has no effect, overall that couldn't be achieved by taking cheap, generic metformin. 

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.

March 25, 2013

Disturbing Study: Both Families of Incretin Drugs Appear to Cause Potentially Cancerous Changes in the Pancreas

Researchers just published a study in the journal Diabetes in which they autopsied the pancreases of 20 people with diabetes, 12 of whom were taking incretin drugs as well as those of 14 people without diabetes. Most had died of stroke or head injuries, leaving their pancreases in excellent condition.

The researchers wanted to see if, in fact, as claimed, the incretin drugs--the drugs that raise the concentration of GLP-1 or mimic GLP-1--cause an increase in the beta cell mass. These drugs have been promoted with the promise that they do, that they regenerate the pancreas. This is one major reason doctors prescribe them even when they appear to have no significant impact on their patients' blood sugars.

What the researchers found when they conducted rigorous studies of these pancreases found should make anyone taking any drug that increases the effect of GLP-1 completely rethink their drug strategy.

The study is Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with increased Exocrine Pancreas Dysplasia and the potential for Glucagon-producing Neuroendocrine Tumors. Alexandra E Butler et al. Published online before print March 22, 2013, doi: 10.2337/db12-1686. Diabetes March 22, 2013

These Drugs Appear to Grow Lots More Beta Cells and Alpha Cells, But they Are Abnormal

What they found is this: These drugs do indeed appear to grow huge numbers of new beta cells and alpha cells in these people's pancreases. People with diabetes taking the incretin drugs had more than three times as much beta cell mass and alpha cell mass as people with diabetes not taking incretin drugs.

Unfortunately, the study also found that these cells were not growing in their normal patterns. They were found in  "eccentrically shaped islets" and "in association with duct structures."

These abnormal beta and alpha cells were only found in the people who had been taking incretin drugs for a year or more, not in people with diabetes. Moreover, the researchers comment that the structures found in association with the pancreatic ducts were of the kind that are found in people with pancreatitis.

Even worse, the researchers found "glucagon expressing microadenomas" in three cases. An adenoma is a benign tumor made of glandular tissue which has the capacity of turning malignant. None were found in the people with diabetes who were not taking incretin drugs.

A glucagon-expressing neuroendocrine tumor was also found in one of the patients taking Januvia.

The researchers point out that,
Moreover, since the standard of care of a pancreatic neuroendocrine tumor, because of the risk of conversion to malignancy, even if benign, is surgical resection [i.e. removal], patients exposed to incretin therapy would seem to be at increased risk of requiring pancreatic surgery.
Pancreatic surgery, even if it doesn't require the removal of your pancreas is very likely to damage it to the point where you become fully dependent on insulin. And that's the good outcome. The bad outcome is that they don't get all of the tumor, which converts to malignancy and you die of pancreatic cancer.

More importantly, the chances of doctors even noticing that one of these drugs is growing a tumore on your pancreas is nil--until it has grown to where it blocks ducts and causes extreme pain. The people autopsied in this study died of other causes unrelated to their diabetes or the health of their pancreases. The tumors they were carrying were unknown to their doctors.

The researchers that the causative factor here appears to be is the action of high levels of GLP-1 since both families of drugs caused the abnormal cell growth. Because of that, the same problems are almost certainly being caused by the newer incretin drugs, Onglyza, Victoza, Trajenta and any other DDP-4 inhibitor or GLP-1 mimic.

Since there were already troubling signs of pancreatitis and other kinds of adenomas associated with some of these newer incretin drugs while they were still in the testing phase, while it took many years for the possible association with pancreatitis to emerge with Byetta, these new drugs may be even more dangerous than Januvia and Byetta.

Talk to Your Doctor and Show Him or Her the Link to this Article Immediately

Tell them to hunt up the full text version. (I have read it.) It is compelling reading and should make any doctor not on the payroll of a drug company seriously reconsider prescribing any of these drugs. 

That said, I fully expect to see this result spun by the drug companies, because the study also found that these drugs increased beta cell mass, something the drug companies have been hoping would turn out to be true.

But as these researchers point out, these new beta cells appear to be immature beta cells that are not functional.  Some are expressing both insulin and glucagon, a characteristic of fetal human cells but not those of adults. And as they note, too. These people were all diabetic when they died, though they had 3 times as much beta cell mass as a normal person. Obviously, these beta cells were not the kind we want to fill our pancreases with.

And of course, the cost of this increase in  beta cell mass was to fill the pancreas with invasive structures made up of a kind of fetal beta cell that isn't usually found in adults. Cells that are clumping together into glandular tissues aaround the pancreatic ducts in ways that aren't normal and, long term, may be far from benign.

Since there is no way to monitor what is going on in your pancreas without opening you up and taking a slice or two, the cost of any beta cell mass growth is obviously much too high.

March 11, 2013

March Diabetes News Snippet Post

Here are all the news items posted in March:

Jenny said...
People taking Byetta, Victoza, Januvia, and Onglyza had less heart failure than those not on these drugs.

However, it is likely this is because Avandia and Actos CAUSE heart failure, rather than that these other drugs prevent it. People are rarely put on both families of drugs at once.

It may also be because these GLP-1 related drugs are mostly prescribed to affluent, younger people with diabetes and good health insurance, while poorer people are put on the cheap sulfonylurea drugs which are now known to raise the risk of heart attacks.
Jenny said...
Paleo fans will probably ignore the news that Mummy CT Scans Show Preindustrial Hunter Gatherers Had Clogged Arteries. From the report "The researchers performed CT scans of 137 mummies from across four continents and found artery plaque in every single population studied, from preagricultual hunter-gatherers in the Aleutian Islands to the ancient Puebloans of southwestern United States."

So plaque probably is some byproduct of an adaptation in the way humans process calcium--probably one that is a byproduct of the genetic changes that led to our species' distinctive bigger brains and smaller digestive tracts.

The Paleo diet is useful in helping cut back on junk food, but the idea that ancient humans were healthier than we are is almost certainly a fantasy. The life expectancies of junk food chomping modern day humans is far longer than that of any pre-agricultural peoples, if only because we have effective treatment for injuries and contagious diseases.
Jenny said...
Exposure to DDT in womb results in high blood pressure decades later.

I remember playing outside in the summer in 1954, and the spray truck passing by spraying huge clouds of DDT. We would take deep breaths of the stuff which had a curious smell. Later, before we went to sleep, my mom would spray my bedroom with it and then I'd crawl right into bed.

Maybe my high blood pressure isn't so mysterious!
RLL said...
Having been, along with sibs, the victims of enraged ground wasp nests, my favorite revenge at 8-10 years old was DDT to the beasts.
Jenny said...
A newly discovered, fatal virus works by activating DDP-4 receptors. However, the diabetes drugs (Januvia and Onglyza) that suppress these receptors do not inhibit the virus.

Reuters: Scientists find how deadly virus infects human cells
Jenny said...
More problems with all incretin drugs--Byetta, Januvia, Onglyza, Victoza, etc. How many people will suffer life changing complications before the FDA acts? I bet your doctor is completely unaware of this ratcheting up of concern.
Jenny said...
A bakery is found to have put sugar in its sugar-free baked goods. The really sad part is that no one seems to understand that the FLOUR in the baked goods is digested into glucose every bit as toxic to people with diabetes as the sucrose. (See last line for what I mean.),0,7328666.story
Jenny said...
Industry strong-arms EPA onto allowing another very dangerous chemical to stay in your drinking water.
Jenny said...
This is to Skippy Pea, I deleted your comment because you had what looks like a ununintended Autocorrect" issue, but the answer to your question is that I don't recommend any protein meal replacements. I don't think they help with dieting and the ingredients are usually cheap omega 6 oils, chemical additives, and poor quality proteins. Why not try some Greek Yogurt with nuts and perhaps some berries instead?
Jenny said...
Victoza (Liraglutide) does not provide significant weight loss in a new study. This reinforces my belief that it isn't as effective a drug as Byetta, while causing much more troubling side effects.

It produced only 4% more weight loss than a worthless placebo. That's 8 lbs lost more than on placebo for someone weighing 200 lbs--which you can easily accomplish without drugs by eating a very low carb diet for a month.

Note that this was on a high dose regimen, and that this drug has been connected with both thyroid cancer and pancreatitis at normal doses.
Jenny said...
Some new research supports the "hygiene hypothesis" that Type 1 Diabetes is becoming epidemic because kids are growing up too clean and not encountering bacteria etc at critical stages of the development of the immune system.

Practical takeaway: let your kids play outside in real dirt when they are young and don't use antibiotic soaps.
Jenny said...
Potent statins linked to acute kidney injury. "Potent statins" are defined as:

Rosuvastatin (e.g. Crestor) at doses of 10mg or higher.
Atorvastatin (e.g. Lipitor) at doses of 20mg or higher.
Simvastatin (e.g., Zocor) at doses of 40mg or more.
Jenny said...
Interesting but very small study about the impact of supplementing with Vitamin D on various genes. Note that quite a few much larger studies have found ZERO impact of such supplementation on Type 1 diabetes, MS, or any other already existing autoimmune condition. If there is a benefit in supplementing with Vitamin D it occurs only before you have developed an autoimmunity.

Also note that they did measure blood levels after the supplementation which ended up on average in the low end of the normal range at 32 ng/ml. They did not observe what happens if you oversupplement and reach the much higher levels where nasty things can start happening to your calcium metabolism.
Jenny said...
The One Touch Verio meter has been recalled. Details here:
Jenny said...
Duh. Tech devices don't make significant changes in A1c--when not coupled with INFORMATION about how to really lower blood sugar.

You can lower your blood sugar dramatically without using any technology but a blood sugar meter by using this technique:

How to Lower Your Blood Sugar
Jenny said...
Scientists discover how Metformin stops cells from being cancerous--it blocks overproduction of inflammatory cytokines.

Science Daily: Scientists Discover How Drug Prevents Aging and Cancer Progression
Jenny said...
High potency statins--high dose Lipitor and Crestor, for example, raise the incidence of hospitalizations for acute kidney injury.

Instead of FaceBook, I'll be Posting Diabetes Tidbits in the Comment Section of Monthly Posts

I've had it with FaceBook. I can't control the ads they show people who come to my page, which are invariably for scams that prey on people with diabetes. I'm tired of channeling a steady flow of people with diabetes into the greedy hands of FaceBooks's abusive advertisers.

Even worse, after I had recruited 1700+ people to my FB page, FB stopped showing most of them my updates, telling me I'd have to pay upwards of $100 each time I posted if I wanted the people who had subscribed to my page to see these updates.

FaceBook's belief that they have a right to spam people who like my page with damaging ads while withholding the useful information I was posting from these same subscribers is criminal.

And to add insult to injury, since FB scrolls posts into hiding very fast, much of what I have posted over the past two years has for all practical purposes vanished and is not accessible via search engine, further ensuring that people won't ever see it.

So I will be killing the FaceB ookBlood Sugar 101 page,  if that is possible, and posting new material only in places where I control the advertising and where I can be sure that everyone who subscribes will see the feed.

This blog and my web pages are under my control and the blog, unlike FaceBook posts, is fully searchable by Google, which means that hundreds and sometimes even thousands of people get to read the posts I put on the blog, even years after they are made. (Right now the page about Metformin I posted back in 2006 is among the top 3 pages visited on this blog each month, and it still gets a comment or two every week.)

I like having a place to note small bits of Diabetes news that didn't rise to the level of needing a full blog post. That is why I stuck with the FB page even after they started cutting down on who could see the page. So to continue being able to feature news snippets what I've decided to do is this:

Each month I will start a new post here on this blog in which I will post the month's minor news items in the comments section. Visitors are free to comment on these snippets, though I will ask that you keep your comments short and limited to the subject of the latest snippet. Comments that don't follow this guideline will not be made public.  

I know this will cut down on the number of people who see my posts, but the comments on my FB page make it very clear that very few people who have liked the page have bothered to check out any of the substantive information available on the Blood Sugar 101 web site.

Since FB's format makes it impossible to conduct ongoing discussions in a way where people can easily follow them, the page failed in its goal, which was to help spread the information available on the main site and help people improve their health.

To ensure you get the monthly post and comments, you can subscribe to the blog (or its comments, separately) via a blog reader like The Old Reader or Feedly.

For those of you who wonder why I have been posting so few substantive blog posts of late, the reason is simple. There is very little news that comes up that hasn't already been discussed in an earlier post here on this blog.

There are currently 552 posts on this blog, which you can search using the search box you will find in the right hand column of this page. They discuss just about every topic that comes up in the news, whether it be the worthlessness of rodent research, the problems with the A1c test, or the value of various drugs and surgeries.

So for most new news items, all that is required on my part is a line or two of comment. The substantive discussions on related topics are already available here and life is too short for me to spend many hours of my day rewriting them for people too lazy to look them up!