Jun 262011
 

Today the Internet is full of news about a new drug called dapagliflozin, for Diabetes. The results of a two year study were presented to the public by the makers of the new drug -- Bristol-Meyers and Astra-Zeneca.

Reuters (1) had a very brief news bulletin saying dapagliflozin is effective “but the companies said more bladder and breast cancers have been seen in patients treated with the drug.”

Medical News Today (2) wrote a more detailed article saying that the two year study demonstrated that dapagliflozin was effective but there were nine cases of bladder cancer and nine cases of breast cancer in the treatment group as opposed to one case of bladder cancer and one case of breast cancer in the control group. The article stated the "Elisabeth Svanberg, the vice president of development for Bristol-Myers, believes the difference in cancer risk is most likely "a numerical imbalance. Those occur in clinical trials.""

The press release from Bristol-Meyers and Astra-Zeneca (3) was widely circulated by the news media. The San Francisco Chronicle (4) said, “A two-year study of Bristol-Myers Squibb Co.'s and Astra-Zeneca Inc.'s experimental diabetes pill dapagliflozin showed it was safe and effective.”

Bloomberg (5) was a little more objective. It said that two years long study showed that the drug was effective but had more breast and bladder cancer than on standard drugs.

It is hard to look at the headlines and figure out what is going on. They say there were nine cased of bladder cancer and nine cases of breast cancer in the treatment group and only one case of bladder cancer and one case of breast cancer in placebo group. Then they say that the drug is safe and effective!

A detailed study of the literature shows that there is element of truth in both. (The literature is all provided by the drug company since there is no independent research on this drug.) The two year study showed that the drug was modestly more effective than the standard drugs. The study group  had more bladder and genital infections than the standard group. So far the company has data on 5,748 patients on dapagliflozin and 3,156 on the standard drug (glipizide). There have been nine cases each of bladder cancer and breast cancer in dapagliflozin and one of each in glipizide group. The drug company believes that this is just a coincidence.

I personally believe that we should be very careful to introduce an entirely new class of drug into the treatment regime unless the drug is unequivocally effective and safe. Dapagliflozin is only modestly more effective than glipizide. Dapagliflozin acts by increasing the sugar output in the urine. No other drug does that. The increased sugar in the urine causes increased infections in the short term but we do not know how it will affect the bladder and kidneys in the long term. Diabetes is a lifelong condition. What will happen to the kidney, ureter, and bladder epithelium after ten years of exposure to high levels of glucose is not known at the present time.

I am going to withhold judgement till more data is available, preferably from clinical studies that are not sponsored by the drug companies. There is no hurry to use this drug. It is not a whole lot more effective than the drugs that have safety data from over thirty years of use.

References:

  1. http://www.reuters.com/article/2011/06/25/diabetes-bristol-dapagliflozin-idUSN1E75O02520110625
  2. http://www.medicalnewstoday.com/articles/229643.php
  3. http://www.marketwatch.com/story/investigational-compound-dapagliflozin-added-to-metformin-sustained-reductions-in-blood-sugar-levels-in-adult-patients-with-type-2-diabetes-in-two-year-study-2011-06-26?reflink=MW_news_stmp
  4. http://www.sfgate.com/cgi-bin/article.cgi?f=/g/a/2011/06/24/bloomberg1376-LN9OBH0D9L3501-662FN34IT1NSKMR4FRB6H4PAKN.DTL
  5. http://www.bloomberg.com/news/2011-06-25/bristol-myers-astrazeneca-diabetes-drug-shows-bladder-breast-cancer-risk.html

 

 

 

 Posted by at 8:25 am
Jun 242011
 

Last week, the Supreme Court's decision to exempt generic drug makers from state court lawsuits claiming deficiency in medication labeling is a boon to all drug makers. In addition to helping the generic drug manufacturers, brand name manufacturers can now claim that their products are superior because patients who are harmed by them can still sue.

It really makes no sense that brand name manufacturers can be sued while generic drug manufacturers cannot be sued for labeling deficiencies.

On the other hand, the whole business of suing drug manufacturers because they failed to list a particular side effect on the product label makes little sense. The labels are already too long, poorly written, and in such small type that few read them . It is highly unlikely that a patient would not have taken that medicine if one more side effect was added to the label. If patients really read and worry about the side effects listed on label, they would not take any medicines 🙂

 

 Posted by at 8:28 pm
Jun 142011
 

Homeopathy is popular all over the world. The theory of homeopathy defies all known principles of science. The first principle of homeopathy is that “like cures like.” If you have allergies to pollens, then taking pollens will cure you of allergies. If you have sneezing and sniffles, like with a  common cold, then taking onion extract (which causes sneezing and sniffles) will cure you. There is no way to argue for or against this first principle. The second principle is that if you dilute a solution of the medicine it continues to be as effective as the original. And that if you continue  diluting until there is not even a single molecule of the original medicine left,  it still remains effective. This defies all reasoning. The proponents believe that there is some power or force that cannot be seen, observed or measured that is transferred from the original medicine to the most dilute solution. Such a supernatural force is beyond the realm of science.

Homeopathy was started by Samuel Hahnemann in Germany in 1796. “Mainstream medicine” at the time consisted of strong purgatives, bloodletting by leeches and various drugs with toxins like mercury. Even if a patient was strong enough to survive pneumonia or some other infection, the treatment was sure to kill him.  At that time homeopathy was superior to “mainstream medicine.” No wonder homeopathy became very popular.

Homeopathy is the best example of the power of a placebo. Homeopaths are good listeners and are caring individuals. They spend a lot of quality time with their patients and prescribe medicine for their patients. The medicine is supposed to be specific for a particular patient. The homeopath and the patients truly believe that it is a specific antidote for the patient’s illness. This belief is the reason for the success and the popularity of homeopathy.

We can all learn a lot from the placebo effect. Most clinical trials show that almost 30% of patients receiving a placebo benefit from the treatment. A lot of medicines do no better. The more intensive the placebo regime, the higher the benefit. For example if the placebo treatment is some “fake” surgery then the results are even better. Unfortunately, surgical device manufacturers have taken advantage of this effect. They produce clinical studies comparing some new surgery, using their patented surgical device, against the standard medical treatment. The surgery almost always wins. The FDA approves the surgical device and a new surgery is introduced to the world.

We must require that any new surgery be compared to established surgery. If there is no established surgery then the clinical study must include “fake surgery.” The fake surgery, called sham surgery or sham group, would involve some surgery that appears real to the patient. Only if the new surgery is clinically superior to the sham surgery, should the FDA allow it to be marketed.

 

 

 Posted by at 7:03 am
Jun 112011
 

The figures are stunning. A promoter placed billboards near a number of Los Angeles freeways advertising Lap-Band ® surgery to “get thin”. In just two years there were 100,000 calls to the advertiser. Ten thousand of these callers had the surgery done. At least four of them died due to surgical  complications (1). It is not known how many others had major complications requiring further surgery. An independent clinical study has shown that gastric banding surgery has a major complications rate 40% of  in the subsequent five years. Each year after that another 3 to 4% of people will develop complications (2).

This can only happen in the US. Makers of drugs and medical devices have unlimited freedom to advertise to people. They can make the most inviting commercials and run them so many times that even a skeptic begins to believe. As they say, if you tell a lie a thousand times it becomes the truth.

Only the FDA stands between advertisers and the public. The FDA has limited staff, lack of expertise in specialized fields, and is under pressure from Congress and industry to approve drugs and devices as quickly as possible.

Once a new surgical device (or medication) is approved, the industry claims that it is both safe and effective since the FDA has given the go ahead.  But their circular logic fails to take into account that the original studies upon which the FDA bases its decision are most often sponsored by the very companies asking for approval. One such surgery is Bronchial Thermoplasty or Bronchial Thermal Cautery. This surgery is being promoted for the treatment of severe asthma. The clinical studies are few and are all done by the promoter. I can just visualize billboards advertising the latest surgery for asthma. There are millions of asthmatics in the US -- the number that will suffer from this ineffective and potentially dangerous surgery remains to be seen.

References:

  1. Los Angeles Times June 11, 2011
  2. Suter M, Calmes J, Paroz A, et al. A 10-year experience with laparoscopic gastric banding for morbid obesity: high long-term complication and failure rates. Obesity Surgery. 2006;16: 829-835.

 

 Posted by at 6:55 am
Jun 092011
 

On June 8, 2011, twenty years after approving simvastatin (Zocor®), the FDA outlined the dangers of using 80 mg dose of simvastatin. (1) The FDA also recognized that simvastatin interacts with certain drugs and can cause harm to patients as a result. Simvastatin belongs to a group of drugs called statins which are used to lower cholesterol. They work by inhibiting a liver enzyme that is essential in the production of cholesterol.

All statins are known to cause muscle damage. When the damage is less severe,  muscle pain (myopathy) results. With more severe destruction  (rhabdomyolysis) there can also be kidney damage.

A study published in 2008 found that using 80 mg a day of simvastatin results in 0.9% incidence of myopathy and rhabdomyolysis. (2) That is almost a one in a hundred chance of a serious side effect. This fact combined with the fact that about two million Americans take 80 mg of simvastatin every day, is cause for alarm. (3)

Dr. Nissen has been advocating the removal of 80 mg dose of simvastatin since 2004. “For every three patients protected from cardiac events by the drug, one patient suffered muscle damage,” says Steven Nissen, chief of cardiology at the Cleveland Clinic. Nissen calls the FDA labeling change "seven years late." (4)

It takes years to fully understand the side effects of a particular medicine. It is particularly difficult to know how patients will be affected when they are taking multiple prescriptions. However the FDA typically requires only trial of one to two years for  new drugs and drug interactions are not generally tested.  Once a drug is approved it is used along with other drugs in combinations that were never tested. When a drug interaction is found, it takes years for the FDA to make a final determination. The drug companies protest any change of labeling and the FDA must go through a long, slow process.

References:

1. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm accessed June 9, 2011

2. The SEARCH Collaborative Group N Engl J Med 2008; 359:789-799 August 21, 2008

3. http://abcnews.go.com/Health/HeartDisease/fda-restricts-high-dose-statin-zocor-cholesterol/story?id=13802167 accessed June 9, 2011

4. http://yourlife.usatoday.com/health/medical/story/2011/06/Simvastatin-can-damage-muscles-in-high-doses/48208588/1 accessed June 9, 2011

 

 

 Posted by at 1:58 pm