Novartis Blood Pressure Medication Runs into Trouble
by Gary Pepper, M.D.
Editor, Metabolism.com
In 2007 a new type of blood pressure lowering medication was brought to market by Novartis Pharmaceutical Company. This medication by the brand name Tekturna (aliskiran) works by blocking hormones that make up a circuit from the kidney to the blood vessels know as the RAAS system. This mechanism is distinct from all other blood pressure lowering medications available. By working via a completely novel pathway to lower blood pressure doctors were given another potent weapon in the war on high blood pressure. A second medication, Valturna, which combines an established blood pressure medication with Tekturna, was released by Novartis to the public in 2009. These drugs have been extremely popular due to their effectiveness and apparent freedom from serious side effects.
A warning about this class of drug was issued by Novartis, 2 weeks ago when it was forced to end the Altitude drug study due to apparent unforeseen complications in patients using Tekturna and Valturna. The study found a small but significant increase in stroke in diabetics with renal disease who were using these drugs. Although the group of patients in the Altitude study are up to 12 times more likely to develop stroke or heart attack under normal circumstances, Novartis had no choice but to end the study and issue a warning to the health care community about limiting the use of these drugs.
In my own practice I have found Tekturna and Valturna to be extremely effective and well tolerated. A survey of my colleagues revealed the same findings. Diabetes and high blood pressure very commonly occur together and national guidelines stress the need for excellent blood pressure control for diabetics to help prevent heart, kidney and eye complications of this disease. For doctors treating diabetics who recognize these patients as particularly high risk, having to significantly cut back or eliminate the use of Tekturna and Valturna is creating major concerns. Within the past week I have had to counsel numerous individuals about these issues and the solution is far from easy. For instance, one man with diabetes and early kidney disease and heart disease, with borderline high blood pressure despite using 4 different types of blood pressure medication including Tekturna has to decide with me, which is the greatest risk, going off the medication resulting in a rise in his blood pressure or continuing a drug which may pose a risk of its own.
These discussions are going on in doctor’s offices throughout the country with no good solution in sight. The only certainty is a flood of ads by lawyers which begin, “Have you ever been on Tekturna or Valturna….”.
Once a common solution for the Miseries of Menopause, hormone replacement therapy (HRT) with estrogen was abandoned almost overnight in 2002 with the publication of the Women’s Health Initiative (WHI) results. The WHI did not dispute the fact that HRT is the best method of reversing post-menopausal symptoms such as hot flashes and insomnia but it did overturn some cherished beliefs as far as women’s heart health is concerned.
Women have a much lower risk of heart attack then men until they reach menopause. At menopause when the ovaries stop making estrogen the risk of heart attack climbs rapidly until it equals that of men. Common sense suggests that if losing estrogen causes increased heart attack risk then replacing the estrogen should prevent this. What the WHI appears to show is that HRT does not protect women from heart disease, but may actually increase the risk above the normal post-menopausal risk. Worse yet is the WHI conclusion that HRT increases the risk of breast cancer and of blood clot complications (thromboembolic disease). It is no wonder that in 2002 HRT took its place with smoking as the scourge of womens’ health.
Since that time scientists have reevaluated the WHI data and more work on HRT risk versus benefit has been done. What is evolving from this reassessment is that the use of progesterone in the WHI participants and the time from onset of menopause until the time HRT was started, both play important roles in how often women developed heart disease or cancer. Additionally, a new class of drugs when use together with HRT may block the cancer risks associated with HRT. In Part 2 of this article I will be covering these aspects. Stay tuned!
Gary Pepper, M.D.
Editor-in- Chief, metabolism.com
The lawsuits against Avandia are being prepared and opportunists are lining up for a payday. Unfortunately, everyone else will wind up a loser, and here’s why.
Avandia, one of only two available medicines with unique properties to treat diabetes, was approved in 1999. From the very first day Avandia was approved a heated debate arose whether Avandia or its sister drug, Actos, was the better drug for diabetes treatment. Both had similar abilities to lower blood sugar and both had the same downside of causing significant weight gain and fluid retention. Avandia showed a slightly worse effect on cholesterol profiles which convinced many diabetes specialists to choose Actos over Avandia. The choice between drugs has also been heavily influenced by cost considerations such as whether the drug was covered by the patient’s insurance carrier. I personally treated numerous patients with both drugs and found them about equal in all respects.
The lawsuits against Avandia will contend that the medication caused heart attack or stroke. The truth of this contention is very much in question, but the murkiness of the water doesn’t stop the lawyers from trying to take a bite out of the flesh of GSK (GlaxoSmithKline), the maker of Avandia.
Several years ago research studies seemed to indicate a small increased risk of heart attacks in users of Avandia. Ever since there has been a heated debate about whether this was a true risk or just the result of overly aggressive interpretation of the available data. There are two major analyzes on the subject of heart attack risk with Avandia. One, written by a doctor on the payroll of a competing drug company, looked at results from 14 thousand patients on Avandia and found a small increased risk of heart attack or stroke and the other study analyzed another 14 thousand Avandia users and found no such association. Under pressure from the public, in 2007 the FDA placed a strong warning on the label of Avandia regarding the possibility of the drug causing heart disease, but Avandia was permitted to remain on the market. The FDA warning was updated and upgraded in 2010. The publicity surrounding Avandia’s potential risks basically halted the use of the drug in the U.S.
Now enter the opportunists. Advertisements fill my email in-box from lawyers looking for customers who want to sue the drug manufacturer in class action law suits. Try goggling “Avandia side-effects” and you will find the first several pages of results are ads looking for lawsuit clients. In the last month I received two requests for patient records from these lawyers. Both patients had heart disease at the time they started the medication. One patient who recently died was over 80 years old, and the other who had significant heart disease and other diabetes complication to begin with, is still alive more than 7 years after treatment with Avandia. I wonder how much benefit these patients received from the medication which allowed them to survive as long as they did despite all the other problems they had related to their diabetes.
Why should you care about whether a small army of opportunists each get a few thousand dollars from the drug manufacturer and a few lawyers become millionaires? Because it is just this sort of legal action which is convincing drug makers to back away from developing other potential diabetes treatments. It takes a decade and a billion dollars to bring a new drug in front of the FDA. This doesn’t include the cost of developing drugs which fail to even make it to FDA review. Then the FDA approval process is tortuous and uncertain. Passing this hurdle, any new drug can come under attack (like Avandia) for “possible” side effects making the company vulnerable to devastating legal costs and bad publicity. It isn’t economically feasible to develop new diabetes drugs in the United States. As a result, new drug development is grinding to a halt. We will all suffer due to lack of innovation, not only for diabetes treatment but for treatment of many other dangerous diseases.
The adrenal glands sitting on top of the kidneys make several hormones critical to life. The central part of the adrenal makes the hormone we refer to as adrenalin, technically from the group known as catecholamines. This is the stress responsive hormone causing rapid heart rate, sweating, increased mental alertness, preparing the body for “fight or flight”. The outer portion of the adrenal makes the hormone cortisol, also known as cortisone. Cortisol maintains, among other things, the blood pressure, fluid and salt balance. Without sufficient cortisol production by the adrenals, life cannot be sustained. What is surprising is that excess cortisol can be as harmful to health as insufficient cortisol.
Deficient cortisol production is referred to as adrenal insufficiency (Addison’s disease is one form of this), while excess adrenal function is termed Cushing’s Syndrome. During certain types of stress such as severe infection the adrenal gland can produce up to 10 times the normal amount of cortisol. If cortisol levels remain elevated for prolonged periods of time the hormone’s destructive nature is revealed by the break down of soft tissue such as skin and muscle and weakening of the immune system with frequent and aggressive infections occurring sometimes with fatal outcome. Heart disease has not been associated with high cortisol levels until a recent study suggested this possibility.
Researchers from the U.K. examined morning cortisol levels in 1066 men and women with Type 2 diabetes participating in the Edinburgh Type 2 Diabetes Study. A positive relationship was discovered between cortisol levels and the occurrence of heart disease such as heart attack and angina. The higher the cortisol levels were the greater the risk of heart disease. Cortisol levels in diabetics were found to be higher than in non-diabetics, in general. The researchers could not explain why the cortisol levels caused heart disease or why levels were higher in diabetics. (From the April edition of the Journal of Clinical Endocrinology and Metabolism 95:1602-1608).
‘Adrenal fatigue’ is a recently proposed diagnosis used to explain a variety of general symptoms such as fatigue, moodiness, muscle aches, and diminished mental function. Supposedly, adrenal fatigue results from mild impairment of cortisol production. Practitioners who diagnose “adrenal fatigue” are prescribing synthetic versions of cortisol as treatment. The possibility of heart disease resulting from excess cortisol should be a factor that patients and medical professionals must consider before embarking on adrenal “supplementation” programs.
This information is for educational purposes only and is not intended as medical advice or treatment.
Several years ago studies suggested that high levels of homocysteine, a naturally occurring amino acid in the blood, could be harmful to cardiac health. B vitamin supplementation is known to lower blood levels of homocysteine. According to the thinking at that time lowering homocysteine levels by taking B vitamins such as B6 and Folic acid should then improve cardiac health. A great deal of publicity surrounding the supposed cardiac benefits of these vitamins led to the promotion of prescription strength B vitamin preparations such as Folbee. These expensive vitamin preparations were then routinely prescribed by physicians for cardiac protective purposes.
Since then several large studies showed no cardiac benefit of lowering homocysteine levels. Worse still, a study just published April 28, 2010 in the Journal of the American Medical Association shows that B vitamin supplementation in diabetics with kidney problems can lead to a doubling of risk of heart attack, stroke or dying. Diabetics with kidney disease are already at higher risk for developing these problems but adding the B vitamins makes the situation much worse. Additionally, kidney function declined faster in those on B vitamin supplements.
The lesson here is to be careful before adopting new therapies based on unsubstantiated research, particularly if you are more vulnerable due to pre-existing medical conditions.
Gary Pepper, M.D., Editor-in-Chief, metabolism.com
The mission of the The Thyroid Project is to encourage sharing of information and experience between the public and the medical community about the treatment of hypothyroidism (low thyroid function). For at least the past few decades there is a growing awareness of “something missing†in the way suffers of hypothyroidism are treated for their disease.
Too many patients, as documented in an on-line study of 12,000 individuals conducted by the American Thyroid Association published in June 2018, (https://doi.org/10.1089/thy.2017.0681) , complain of persistent symptoms of hypothyroidism despite what their doctors believe is successful treatment with levothyroxine (brands include Synthroid, Unithroid, Tirosent, Levoxl). We believe something needs to be done to resolve this conflict between patients and their doctors.
Without effective intervention the early stage of type 2 diabetes known as prediabetes carries a high risk of progressing to outright diabetes. Metabolism.com provides an up-to-date summary of recommendations from national authorities, for preventing and possibly reversing this life long affliction
Diabetes can be defined simply as elevated blood sugar levels. What exactly is high blood sugar and when should someone be concerned about their level? Does having prediabetes mean diabetes is around the corner? Metabolism.com tackles this tricky but important topic in this comprehensive review.
By Gary M. Pepper, M.D. Ozempic, Rybelsus, Trulicity, Wegovy, Saxenda are the central players in the weight loss craze sweeping across the globe. Metabolisim.com has been monitoring this phenomenon from its beginnings in 2008 with its report “Lizard Spit Reduces Blood Sugar and Appetite”, regarding the first drug in this class, Byetta (exenatide). Caught In the middle of the current chaos are the medical experts who treat diabetes and have been prescribing these medications for more than a decade. Here is a brief commentary from one such board certified endocrinologist; “I started treating Type 2 diabetics with GLP-1 agonists more than 10 years ago. In some respects, these medications have revolutionized the treatment of diabetes by lowering blood sugar effectively and promoting weight loss at the same time, a unique combination of benefits. Not everyone benefits from these drugs to the same degree unfortunately, and I have seen lots of patients experience unacceptable side effects from them. Nothing though, has prepared me for what is happening now. Too often, I find myself confronting someone who expects me to prescribe one of these drugs just so they can lose weight. Sadly, one extreme example was someone who, despite battling a life threatening medical condition, was insistent on getting a prescription. At the same time my diabetic patients are scrambling to find a place to buy their medications if they can even afford it. It is disheartening, to say the least, and I dread the negative interactions with some of my patients I now face almost daily.”
Off- Label Use
The FDA is the U.S. government’s department tasked with evaluating and approving drugs for specific medical conditions. When a new medication is approved for treating a medical condition by the FDA the agency will, at the same time, set strict guidelines for exactly which patients may use the newly approved drug. When a medication is used “off-label” it means that these limitations are being overridden by the provider for a potential benefit which outweighs the drugs risks. It is a general misconception that off-label means illegal; it does not. This practice has been going on for ages and more than 20% of prescriptions in the United States are prescribed off-label. A common example is the use of beta-blockers (approved for heart problems) for the treatment of performance anxiety.
GLP-1 agonist drugs, as discussed recently by metabolism.com. were originally approved for the treatment of Type 2 diabetes in adults. In the past few years most of these same medications have gained unprecedented popularity for their “off-label” weight loss benefit. Of the 5 GLP-1 agents presently in U.S. pharmacies only Wegovy (semaglutide) and Saxenda (liraglutide) are FDA approved for treating obesity. Of these two, Wegovy is the newer and had been much more popular that its sister drug Saxenda, probably due to being dosed only once weekly compared to daily for Saxenda and less likely to cause side effects. Due to Wegovy’s soaring popularity, its manufacturer, Novo Nordisk, increased the price of Wegovy two times since its initial release.
