Pharmaceuticals In, Pounds Off

Some of this talk about weight-loss drugs might not seem relevant to childhood obesity, but the connection is, obese children tend to become obese adults. To learn about the possibilities is to fervently wish that our children will never have to experience them firsthand.

Orlistat (generic) comes in two brand names that denote different dosages. It is said to block absorption of 25 percent of the fat in a meal, and is recommended for very obese patients who are coping with the risk factors of hypertension, diabetes, or hyperlipidemia. The daunting list of side effects would seem to preclude any kind of social life.

Lorcaserin is an extended-release tablet that helps people feel fuller with smaller meals, by affecting the brain’s appetite-controlling signals. As expected, it comes with warnings about pre-existing conditions and possible conflicts with other medications. As always, the patient is enjoined to practice good dietary and exercise habits.

Lorcaserin has worrisome physical side effects and even more alarming mental effects, including impaired thinking, decreased alertness, urges to self-harm, and out-of-body sensations. It is not to be prescribed to people under 18.

Metformin is described by a patient Marcia Kadanoff (as told to writer Timothy Hay) as safe, effective, and affordable; not very stressful to the internal organs; and not linked to weight gain. Its primary use is the treatment of diabetes, and it is in fact (although not officially approved as such) also a weight-loss drug. The authors say of this member of the class biguanides:

The medicine does not increase insulin levels in the body, but instead lessens the amount of sugar the body produces and absorbs. As it lowers glucose production in the liver, metformin also lowers blood sugar by increasing the body’s sensitivity to insulin. It also decreases the amount of glucose that our bodies absorb from the foods we eat.

I expected it to work like insulin in pill form and drop my blood sugar (around 180 mg/dl at the time) right away. But… It can take four or five days to experience the full benefit, depending on your dosage.

Some patients experience side effects, which usually subside over time. They might include nausea, stomach pain, gas, bloating, and diarrhea. To prevent these discomforts, doctors like to start conservative and titrate up, which may delay the perceived start of the benefits even more.

Reportedly, gastric distress can be alleviated by avoiding carbohydrates in the diet, or by using the extended-release version of the medication. Also, metformin can block the absorption of Vitamin B12, so that needs to be monitored.

The more serious, alarming, and fortunately rare side effects include hypoglycemia, lactic acidosis, liver damage, and heart failure. On the plus side, metformin is being looked at for a variety of other uses including, paradoxically, heart disease.

Your responses and feedback are welcome!

Source: “Orlistat,” RxList.com, undated
Source: “Lorcaserin,” Drugs.com, 11/13/17
Source: “Everything You Always Wanted to Know About Metformin, But Were Afraid to Ask,” Diatribe.org, 01/08/19
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60-year-old Weight-Loss Drug Makes a Comeback

There was a time when “diet pills” were more liberally prescribed. They would lead the user to alphabetize the closet, scrub the floor with a toothbrush, or simply bounce off the walls. They were basically pure speed, and sometimes the results were far from salubrious.

Then, in the 1990s, fen-phen, a combination of fenfluramine-phentermine, was The Thing for a few years. But all along, reports were coming in about such non-trivial problems as heart valve damage and primary pulmonary hypertension (PPH). Also, hair was falling out of women’s heads. In 1996, its year of peak use, doctors wrote 18 million prescriptions for fen-phen. The next year, fenfluramine was banned by the FDA.

A ton of people sued the Wyeth Pharmaceuticals, which was ordered to make $21 million available for compensatory payments to consumers. Things cooled off for a while, but the amphetamine-like phentermine, even without its former partner, is still an appetite suppressant. Journalist Leslie Goldman writes,

Doctors believe it works by targeting the hypothalamus (the part of the brain responsible for satiety) and boosting neurotransmitters that help minimize hunger and cravings.

In a piece called “The Secret, Scary Way Your Friends Are Losing Weight,” Goldman asserts that although today’s weight-conscious women eat more mindfully and exercise more religiously, many still take pills, and probably do not admit it to their friends. She paints the picture of a culture where the use of pills is stigmatized and thus hidden — although believers do go online to chat anonymously about their secret.

But in real life, some women prefer to promote the illusion that their slim figures are righteously earned. Consequently, their friends don’t cop to having pharmacological help either, because they believe that others are succeeding on diet and exercise alone. This creates a self-reinforcing web of deception.

The way it’s supposed to be

The recommended way to use phentermine is in a limited course, for two or three months at most, and with close monitoring by a medical professional. There are success stories, where the temporary advantage is treated as a jump-start, for psychological encouragement. But as always, the most important thing is to develop a whole new kind of lifestyle, because otherwise, the weight will inevitably return when the prescription runs out.

If a person can pay a lot, and doesn’t mind dealing with shady online sources or the risk of not even getting what was ordered, little things like recommended limits are irrelevant. Nevertheless, the side effects of heart interference and PPH are still in play, and sadly, taking a higher dosage does not lead to more weight loss, but does increase the undesirable side effects.

Ed J. Hendricks of Center for Weight Management in Roseville, CA, reveals that despite the warnings, some doctors have been okay with extended prescriptions all along, like since 1959, when phentermine was first approved. They reason that the risks are acceptable compared to the risk of morbid obesity.

For many years, until the 1980s, the drug was even deemed safe for children. Hendricks writes,

There are no reports of harm from phentermine treatment in either very young or elderly patients. The surveys of obesity medicine physicians cited above indicate that a majority use phentermine in treating adolescents… [O]bservational reports have included patients safely treated with phentermine as young as 3 years…

Clinically significant psychiatric distress similar to that described in the DSM-5 in discussing stimulant use disorders has never been observed in overweight or obese patients treated with phentermine. A phentermine withdrawal syndrome has never been observed or described.

Due to recent studies showing that long-term use does not in fact increase blood pressure or the risk of heart attack and stroke, phentermine is now back in the good graces of the medical world. As a generic drug, it is relatively affordable. Also, official definitions have changed. As one source puts it,

Now that we view obesity as a chronic disease, it’s important to have medications that can be used indefinitely.

Your responses and feedback are welcome!

Source: “The Secret, Scary Way Your Friends Are Losing Weight,” Cosmopolitan.com, 02/12/19
Source: “Off-label drugs for weight management,” NIH.gov, 06/10/17
Source: “Generic weight-loss drug may be safe and effective for long-term treatment,” ScienceDaily.com, 03/22/19
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Big Pharma — Is Suspicion Justified?

Steven Peters of NaturalRevolution.org is admittedly biased — the name of his website kind of tips his hand. If any doubt remains, here is a quotation about Big Pharma:

If this were a terrorist group causing death and destruction like we’ve never seen in any other time in history, the US would be bombing every last one of them out of existence.

In any given year, in U.S. hospitals, more than two million patients are afflicted by ADRs (adverse drug reactions) caused by prescribed drugs. That seems like a lot. Now, imagine how many non-hospitalized people are walking around suffering from adverse reactions to their prescriptions. We can only guess, because ambulatory patients are not kept tabs on by any central agency. Over 100,000 Americans die in a year from adverse drug reactions, a statistic that comes with a price tag of $12 billion.

Granted, people are all different, and some react differently than others to substances concocted in laboratories. Some have previously undiscovered allergies and sensitivities. Some undermine themselves by not revealing what else they are taking when the doctor asks. Many emergency-admission patients are in no condition to provide comprehensive medical histories, or have no one at their side to help.

Plenty of medications need to be titrated, or carefully measured out, until the optimal dosage is established. With so many variables, all meds are not going to work perfectly for everyone all the time. Also, a big part of the problem lies with the protocols by which pharmaceuticals are tried out on healthy people who are not taking other major meds. Peters writes,

But when these new drugs are declared “safe” and enter the drug prescription books, they are naturally going to be used by people who are on a variety of other medications and have a lot of other health problems.

In other words, drugs “generally recognized as safe” have a way of being unleashed upon the public with less than stellar results. This makes patient vulnerable to the same disadvantage as the “end user” who buys a next-generation computer. Too often, a product is released before all the bugs are worked out, and the end-users (in this analogy, the patients) are pressed into service as beta testers.

In the industry, this is known as the post-approval stage of information gathering, another phase in which medical ethics might give way to a conflict of interests. Peters calls on stats from the General Accounting Office showing that for a nine-year period (1976-85), half of all newly released drugs had “serious post-approval risks,” and actually were responsible for heart failure, respiratory arrest, anaphylaxis, seizures, blindness, birth defects, and more.

Selling drugs

Readers, please excuse a personal intrusion from the blog author. In the several orthopedics practices I worked in, the doctors were always men. The offices were often visited by reps from the pharmaceutical corporations, who almost invariably were very personable, model-level gorgeous young women. Coincidence?

Not to put too fine a point on it, drugs are prescribed for many different reasons, some of them having to do with doctors being treated to over $2 billion worth of hospitality annually, at 314,000 events per year sponsored by Big Pharma.

Next, we will discuss weight-loss drugs specifically.

Your responses and feedback are welcome!

Source: “How Big Pharma Scam Patients, and Manipulate Doctors and Scientists,” NaturalRevolution.org, 10/08/17
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The Promising GLP-1s vs. Human Nature

To catch up on what GLP-1s are all about, please consult the previous post.

Lotte Bjerre Knudsen and Jesper Lau, who are both employees of pharmaceutical giant Novo Nordisk, wrote “The Discovery and Development of Liraglutide and Semaglutide” — and who would be more qualified? The big challenges were to make these substances therapeutically effective for type 2 diabetes patients, and to extend the drug’s half-life.

The action of GLP-1s involves the pancreas, GI tract, heart, lungs, kidneys, liver, thyroid, and brain. This very technical paper takes readers step-by-step through the history of how the researchers figured out a generous plethora of astonishing things about liraglutide and semaglutide. Several weight-loss studies are referenced.

Liraglutide has also been approved as an obesity treatment, and has to be injected daily. Semaglutide is injected weekly, and might soon be available as an oral medication. Why are these substances not already marketed in a form that can be taken by mouth? According to Knudsen and Lau,

Oral absorption of small molecules without enhancers mostly occurs in the intestine, and this has been assumed to be the case for peptide-based drugs with enhancers. However, peptide absorption in the intestine is a challenge, as numerous peptidases may degrade substances before they can be absorbed.

So, the trick is to get the drug absorbed in the stomach, and this might be on the horizon. Liraglutide’s most prevalent side effects are nausea, vomiting, diarrhea, indigestion, and constipation, especially during the up-titration phase. In other words, this is a baby-steps sort of drug, whose dosage is meant to be closely monitored by a doctor.

Other known medical risks include allergic reactions, thyroid cancer, pancreatitis, hypoglycemia, kidney failure, and acute gallbladder disease.

The existence of other drawbacks predicts that liraglutide, as least as an injectable, will not catch on in a big way as a weight-loss drug. Many people will simply not sign up for daily sessions with a hypodermic needle unless it is absolutely, life-savingly necessary.
Cost is of course a huge factor. There are discount programs, but the price hovers around $1,000 for supply that lasts three to five weeks, depending on what the doctor prescribes.

Each year in America, more than 5,000 new cases of T2D diabetes show up in patients younger than 20. Just last June, Victoza (liraglutide’s brand name) was FDA-approved as an injectable for children over 10 who need their blood sugar controlled.

In the trials where liraglutide was verified as promoting weight loss, the result was specifically stated as being in combination with an energy-deficit diet, which for many people is the insurmountable problem. The official language is, “as an adjunct to a reduced-calorie diet and increased physical activity.” More than likely, a large contingent of people would fat-logic themselves into eating more than ever, counting on the medication to erase the extra calories.

Your responses and feedback are welcome!

Source: “The Discovery and Development of Liraglutide and Semaglutide,” FrontiersIn.org, 04/12/19
Source: “FDA Approves Liraglutide for Pediatric Patients with Type 2 Diabetes,” PharmacyTimes.com, 06/17/19
Photo credit: Potamos Photography on Visualhunt/CC BY-ND

Liraglutide, a.k.a. Victoza, a.k.a. Saxenda

“GLP-1s” is short for “glucagon-like peptide-1 receptor agonists,” and these hormones come in several varieties. When we eat sugar and carbs, our intestines make GLP-1s to stimulate the pancreas to produce more insulin and less glucagon. The interesting, obesity-related part is that they keep the stomach from emptying too fast, which enhances the feeling of satiety.

This action is imitated by (generic name) liraglutide, branded as Victoza, Saxenda, and Byetta. A recent Childhood Obesity News post described a very expensive document titled “Anti-Obesity Drugs: Global Market Analysis, Trends, and Forecasts,” which includes six sections about liraglutide and its manufacturer.

Novo Nordisk is named as the leading player in the market. Many front-line medical personnel are not comfortable putting the fate of traumatized, struggling, morbidly obese children into the hands of “players,” but that appears to be where we are.

The various section heads also note that the company introduced its anti-obesity drug in India, is developing novel therapeutics, has anti-obesity drugs in the pipeline, and seeks approval for Saxenda as weight-loss medicine in Canada. The document mentions that other diabetes drug manufacturers are trying to “foray into the anti-obesity drugs space.”

The GLP-1s buzz

Victoza started out as a treatment specifically for diabetes patients, and was accepted first in Europe. It seemed to facilitate some otherwise-inexplicable slimming, so it was tested on non-diabetic patients. Salynn Boyles wrote,

The 20-week weight loss study included 564 obese people with body mass indexes (BMI) of between 30 and 40, treated at 19 sites throughout Europe… By the end of the study, the liraglutide-treated patients had lost significantly more weight than either the placebo-treated patients or those who took the oral weight loss drug.

In Europe and India, Victoza was used off-label, meaning for a purpose (weight loss) other than its stated mission (blood sugar regulation). The industry frowns on that, and so does the government, which may be why Saxenda was developed as a separate entity.

Saxenda is indicated for weight management in adults who have type 2 diabetes, but is not a treatment for that condition, nor should it be used by patients who are on insulin. It is definitely meant to be used in conjunction with diet and exercise.

In the U.S., liraglutide was FDA-approved for type 2 diabetes (or T2D) in 2010. There was some talk of another potential off-label use, about which, at that time, Dr. Scott Mendelson wrote:

Having Diabetes Type II has been known to at least double the risk of developing Alzheimer’s Disease… [T]his new type of medication may also help reduce the risk of Alzheimer’s Disease in sufferers of Diabetes Type II, and perhaps even those without diabetes.

(To be continued…)

Your responses and feedback are welcome!

Source: “2019 Anti-Obesity Drugs Report: Global Market Analysis, Trends and Forecasts Through 2015-2024 – ResearchAndMarkets.com,” Yahoo.com, 06/12/19
Source: “Diabetes Drug Promotes Weight Loss,” WebMD.com, 10/11/09
Source: “Selected Important Safety Information,” SaxendaPro.com, undated
Source: “New Diabetes Drug May Help Prevent Alzheimer’s Disease,” HuffingtonPost.com, 04/07/10
Photo credit: davis.steve32 on Visualhunt/CC BY

Gold in Them Thar Pills

In the 1800s, hoping to persuade independent miners to stay in their home state, a northern Georgia assayer gave a speech. But some traveled instead to the California Gold Rush, where renowned American writer Mark Twain interviewed them. The assayer’s original wording was rather uninspired, so Twain remodeled his slogan into the rallying cry, “There’s gold in them thar hills!” and put it in the mouth of a character called Mulberry Sellers, in the novel The American Claimant.

“There’s gold in them thar hills!” became a catchphrase for any situation where someone wanted to point out the opportunity for profit, and it is certainly appropriate to the field of anti-obesity therapeutics. Massive fortunes are made not only from the pharmaceuticals themselves, but from providing information about them.

Costly words

For instance, a report titled “Global Anti-Obesity Therapeutics Market Insights, Forecast to 2025” is available for only $3,900. If that sounds extreme, you ain’t heard nothin’ yet. Another publisher offers a comparable report on China alone for practically the same price, $4,000.

From that company, a complete copy of “Anti-Obesity Drugs: Global Market Analysis, Trends, and Forecasts” can be had for the magnificent price of $5,450 — unless the interested buyer wants more than one license, in which case the price goes up. Their pitch is,

This report provides separate comprehensive analytics for the US, Canada, Europe, Asia-Pacific, Latin America, and Rest of World. Annual estimates and forecasts are provided for the period 2015 through 2024. Market data and analytics are derived from primary and secondary research.

The work begins with general background, and a review of currently available anti-obesity medications, as well as those in every stage of clinical trials. It covers not only pills, but such experimental delivery systems as a micro-needle skin patch. The report recaps what went wrong with anti-obesity drugs of the past. Currently available prescription drugs are reviewed, and their various mechanisms of action explained.

The inquiring customer can also learn about “off-label” products — in other words, medications that are not meant to be, but are, used for the purpose of weight loss. The industry’s handicaps are recognized, with separate chapters devoted to spiraling development costs described as “a major setback” and “a high entry barrier.”

The development of new drugs is described as high on the agenda, despite market restraints. The relevant chapter is titled, “Reluctance among Patients, Physicians, and Payers Hurts Market Prospects.” Still, despite the obstacles, there is optimism, as expressed by another chapter heading, “Anti-Obesity Drugs: A Market Characterized by High Unmet Needs.”

Our pain is their gain

A section is titled, “Key Obesity Statistics: Opportunity Indicator.” The tragedy of the worldwide obesity epidemic and the rising incidence of chronic associated diseases are, to these financial wizards, nothing but “growth drivers,” while weight-loss alternatives are “market dampeners.” Childhood obesity is modestly described as “a market with unmet needs,” and a chapter is titled, “Childhood Obesity — Catching Them Young.”

Online drug stores are congratulated for boosting sales. In analyzing the competitive landscape for the benefit of investors, the report drills down to such specific details as, “CohBar Presents Preclinical Data of CB4209/CB4211 Program at the AASLD Liver Meeting.”

It’s a big, fat world out there

In addition to detailed profiles of a total of 25 pharmaceutical corporations, the volume features detailed analyses of global and regional market perspectives, broken down by country. Europe is touted as “a market with vast potential.” Germany is hailed as Europe’s largest anti-obesity market. Not surprisingly, America is celebrated as the world’s largest market for this genre of pharmaceuticals, and any buyer with $5,450 can lean back, put their feet up on the desk, and read “Top Ranked States in the US based on Fatness, Obesity, and Overweight Regulatory Environment.”

Your responses and feedback are welcome!

Source: “Anti-Obesity Therapeutics Market — A comprehensive study by Key Players: Bristol-Myers Squibb, Eisai, FlaxoSithKline, Novo Nordisk,” Journallic.com, 05/14/14
Source: “2019 Anti-Obesity Drugs Report: Global Market Analysis, Trends and Forecasts Through 2015-2024— ResearchAndMarkets.com,” Yahoo.com, 06/12/19
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