Novartis Blood Pressure Medication Runs into Trouble
by Gary Pepper, M.D.
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….”.
One of the biggest problems with weight loss programs and diets is that even if they work the weight tends to come back on within a year or two. A recent study from the University of Utah of people who underwent bariatric surgery shows that not only do they lose weight quickly, after 6 years they continue to maintain their lower weight. After undergoing bariatric surgery the average weight drop was 35% of the original weight and after 6 years weight loss was still a very encouraging 28%. 75% of diabetics who had bariatric surgery were able to go off their diabetic medications, while improvements were generally seen in cholesterol levels and blood pressure.
Although this study shows a very high success rate, in the real world medical practice I have seen many people who are able to eat their way out of weight loss success after bariatric surgery. Eating small amounts of very high calorie food is still possible and unfortunately is not all that uncommon. Not to say that bariatric surgery is not helpful, because when it works the results can be spectacular, but as always the degree of motivation of the patient is crucial to success.
As a culture we donâ€™t plan for a sudden halt in scientific advancements. Our tendency is to expect progress to be rapid and continuous. My prediction is that in certain areas of medical science we are likely to see not only a halt in progress but a slipping backward. In particular, the realm of medical weight management is in complete disarray at this time. Two new drugs designed to induce weight loss have been shot down by the FDA in the last few months. The first is Qnexa, developed by Vivus Inc. Interestingly, Qnexa combines two drugs already approved for use in the U.S. One of the drugs is phentermine which is a medication used for decades as an appetite suppressant. The other is a common drug used to treat seizures with the brand name Topamax (topiramate) which also induces weight loss. The drug performed admirably in clinical trials with most participants losing over 10% of body mass. The FDA cited excessive risks of the drug in its statement of rejection. One wonders why the drugs are still being marketed separately if they are so dangerous.
The latest drug to be rejected by the FDA is Lorgess (lorcaserin), developed by Arena Pharmaceuticals. This drug, not as effective as Qnexa, produced 5% body mass loss in about half of participants in clinical trials. Lab animals showed a tendency to develop breast tumors when exposed to the medication, adding to the FDAâ€™s decision to reject the drug application based on safety concerns.
I am a strong advocate of drug safety and regulation. On the other hand we know obesity, and with it Type 2 diabetes, is epidemic in the U.S. I regard weight loss as the â€œholy grailâ€ when treating type 2 diabetes and yet it is the most difficult goal to achieve. Any drug which could assist in weight loss is highly desirable in the treatment of Type 2 diabetes. Not only does blood sugar improve with weight loss but also blood pressure and cholesterol readings show declines. All three of these parameters are known to be prime contributors to the main cause of death in diabetics, cardiovascular disease.
It has already been 10 years since the last drug was approved specifically for a weight loss indication. The failure of these two latest medications to achieve approval is certain to cause the pharmaceutical industry to severely curtail if not abandon further investment in this type of drug development.
Why is the FDA so reluctant to approve a weight loss pill? This is a complex issue but requires an answer. A new weight loss inducing medication is certain to be highly anticipated and widely prescribed. Therefore, from the very first day of approval the FDA must take responsibility for the well being of millions of people who are likely to take the medication. We are a society which demands our medications deliver miraculous cures with no side-effects. If someone perceives they have been injured by a medication our legal system is primed to unleash brutal retribution on everyone remotely involved in the approval process. Abuse and injury with a medication designed to cause weight loss is almost a certainty. This is a no-win situation for the administration of the FDA.
I predict it will be at least another 10 years before a medication for weight loss is approved by the FDA. Unless there is a change in the climate of litigation in this country it will take longer than that. In the meantime the only new developments in weight loss drugs will be the result of exploiting appetite suppressant effects which are the â€œside-effectâ€ of medications approved for other purposes.
It seems obvious that cutting away part of the stomach and intestine should cause weight loss. With a smaller stomach and less intestine fewer calories can be absorbed per day causing weight loss. Surgeons who perform gastric by-pass were puzzled however, by how fast their patients showed metabolic improvement after undergoing this procedure. They noticed many of their diabetic patients could be taken off diabetic medication immediately after surgery before weight had been lost. Scientists looking into this phenomena discovered unsuspected ways gastric by-pass improved metabolism.
The intestines produce hormones which regulate blood sugar and appetite. GLP-1 is among the best known of these intestinal hormones. GLP-1 is the basis of a whole new generation of medications used to treat diabetes such as Byetta, Victoza, Januvia and Onglyza. GLP-1 lowers blood sugar, stimulates the pancreas and reduces appetite. After gastric by-pass increased amounts of GLP-1 are produced by the remaining intestine. In a study published in the Journal of Clinical Endocrinology and Metabolism (95:4072-4076, 2010), researchers at St. Lukeâ€™s Hospital in New York discovered that levels of oxyntomodulin, another intestinal hormone that suppresses appetite and acts like GLP-1 on blood sugar levels, is doubled after gastric by-pass.
These exciting discoveries help explain why obese diabetics can often be sent home without any medication to control blood sugar immediately after undergoing gastric by-pass surgery. Although most insurance plans do not cover gastric by-pass surgery, dramatic improvements in patients after the procedure with greatly reduced medication costs may convince insurance companies that paying for the procedure will result in better outcomes and save them money in the long run.
After reading the latest research on the metabolic hazards associated with chubby necks I am more sensitive to the size of people’s necks then ever. Of course I look at the size of my patient’s neck but people who I pass in the street or supermarket may find me staring. Watching TV a few days ago I was startled by a series of people in one commercial for Quicken Loans who definitely qualify for the metabolic high risk category based on neck chubbiness. One after another the characters in this commercial walk on, outdoing each other in this physical trait. Has the chubby neck become the new normal? If so, the incidence of diabetes and heart disease is sure to continue to rise.
Let me know if you agree with my impression, or am I biased by being an endocrinologist?
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 â€œsomething missingâ€ 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.