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Getting to Ozempic: Weight Loss Drugs Through Time

amphetamins diabetes diabetes drug diet fen-phen medical weight loss mounjaro ozempic phen-fen rybelsus semaglutide wegovy weight loss drugs Jul 25, 2023

by Phil Kaplan

In the late 1800s, women were encouraged to perform household duties and “pleasingly plump” was considered the ideal woman.  Curvy.  Buxom.  Healthy.

Portly men were associated with success and affluence.  America didn’t have an obesity problem and what, in the year 2023 might be considered “overweight” was the acceptable norm.

In the 1920’s trends changed, women’s fashion began exposing more leg, and a sleeker look became fashionable, and although we weren’t yet plagued by Insta-Famous super-bodies magnetizing our attention, pleasingly plump was going out of style.

Starvation was the primary approach to weight loss and due to its difficulty and long-term ineffectiveness, an opportunity emerged for those willing to package and sell “a solution.”

It didn’t take long.  Just as shorter skirts were becoming the rage, thyroid hormone was extracted from sheep and pigs and sold as a weight loss medication.  People lost weight.  People developed chronic hyperthyroid conditions.  People developed irregular heartbeats.  Some people died.  But the floodgates were open.

Near 1930 a buzz began around a chemical compound called dinitrophenol (DNP).  DNP resulted in rapid and significant weight loss by acting within the mitochondria to drive up basal metabolic rate.  First released with the words “safe and effective” it had a short run.  There was illness.  There were crippling effects.  There were deaths, and in 1938 DNP was deemed “extremely dangerous and not fit for human consumption.”

A crazy note related to DNP . . . it is sold as a chemical dye ingredient, as an antiseptic, as an herbicide (unsafe for human consumption) and . . . as a fat loss aid by extreme risk-takers in the world of bodybuilding and physique competition.  “If it’ll help me lose fat, I’ll try it.”  That sentiment ignores the high risk of toxicity, the increased thermogenesis (people have died from heat stroke because their body heat elevated rapidly and dramatically from the use of DNP).  But it helps people lose weight and so . . . rational thought often goes out the window.

I digress . . . back to the story . . .

After DNP was pulled, the drug manufacturers began to see the “mass frenzy buying response” that amplified the profit potential of a category of drug that promised weight loss. 

Enter amphetamines. 

Dexadrine was the drug of choice.  Doctors handed out dexadrine prescriptions to any patient complaining of being “too fat.”  The main flaw with dexadrine and the spin-off compounds that followed was . . . addiction.  And with addiction came risk of overdose.  And lots of side effects ranging from tremors to psychosis.  Oh, and death.  For real.

In the 1950’s the FDA took on greater authority, and with the "Amphetamine Control Law" passed in 1951, these stimulant weight loss drugs went away from the realm of “commonly prescribed weight loss solutions.”

And then, the Barbie doll was invented, and a new impossible ideal began to exist for women (if the original Barbie was proportionately grown to 5’6, she’d have a 17-inch waist and a 40-inch bust.  Barbie was the Insta-Famous hot bod of the day.  And she never left.  All of the girls who were 7 or 8 when Barbie was introduced were headed into the massive market of “perfect-little-body-wanters” and the explosive opportunity for riches in drug prescriptions took a massive leap.

In 1965, a different type of stimulant / appetite suppressant called aminorex fumarate was released and it wasn’t long before users of this new obesity control drug started frequenting Emergency Rooms with chest pain.  A disturbingly common diagnosis among these individuals was Primary Pulmonary Hypertension (PPH).  PPH is a rare heart / lung disease where the vessels constrict and pressure is severely elevated.  There is no cure.  It doesn’t get better.  It typically leads to death by way of cardiac arrest.

In 1968 aminorex fumarate went the way of its predecessors.

Do you see a pattern?

A drug shows promise as an obesity treatment, it’s brought to the market, it generates massive revenues, people get sick and die, nobody loses weight healthfully or permanently, the drug is pulled.

I can give you other examples of this recurring scenario, but let’s recognize that from the 1960’s to the 1990’s, obesity skyrocketed, the drug companies found greater funding, and enhanced their lobbying power, and the race to come up with the next “weight loss miracle” was picking up steam.  If something had weight loss as a side effect, all eyes were on it, often regardless of the risks.

The next major release, in fact, the biggest weight loss drug ever, hit the market in 1992.  It combined a stimulant weight loss drug from the 70s, phentermine, with a drug that acted at the serotonin centers of the brain called fenfluramine.  On the drug you were speeding, but your brain told you you’re calm and relaxed.  You don’t eat.  Your brain tells you you’re satiated.

In 1996, over 18,000,000 prescriptions were written for Phen-Fen, and later that year cases of heart lesions, valve injuries, and . . . this will sound familiar if you’ve been reading from start to finish . . . a significant and disturbing emergency of PPH.  I said earlier there was no cure for this condition, but let me lay out the entire picture.  If you take a drug to lose weight, and you develop PPH, you have a choice.  You can die, or, you can get a complete heart and lung transplant and pray.  Or . . . you can stop believing in the next weight loss drug miracle!

It didn’t end when Phen-Fen was pulled, but it did create a bit of caution preceding new releases, as the manufacturers of Phen-Fen had to pay $3.75 Billion in damages, and . . . the lawsuits continue to come in right up until 2022!  This was a costly release in many ways.

After Phen-Fen, Orlistat was the next one to gain public awareness.  It was released under the name Xenical and the marketing said it can lead to weight loss and should be combined with a calorie-restricted diet and exercise.  Hmmph.  Jellybeans can help you lose weight if they come with an order for calorie cutting and exercise!  In fact, users of Orlistat would have been better off with jellybeans. 

Orlistat attracted and clung to fat in the digestive tract and carried that dietary fat out the other end without allowing it to be absorbed.  It doesn’t take a research scientist to recognize that this would clearly interfere with the absorption of Vitamins A, D, E, and K (fat soluble vitamins) but it gets uglier.  The drug led to anal leakage and loose and oily stools.  That one went away in pretty short order.

Other drugs and stimulants that found their way into the market for other purposes found their way into medical prescription for weight loss programs (such as HCG, Adderall, and other drugs for off-label use) but the newest class of drugs are the ones I want to now focus on.  They are injectables with semaglutide as the active ingredient.

FOR AWHILE, SEMAGLUTIDE IS THE WEIGHT LOSS ROCK STAR

Semaglutide acts at the glucagon receptor to alter the output of pancreatic hormones and affect the balance between insulin and glucagon.  It is a Glucagon-Like Peptide agonist, GLP-1.  It found its place as an infrequent injection to help manage blood sugar in diabetics.  Because insulin spikes (due primarily to insulin resistance) is a primary factor in the onset of diabetes, the mechanism of action “makes sense,” not in a curative way, but in terms of it “managing” blood sugar for a brief period of time.

There are many brand names for GLP-1 drugs (semaglutide or liraglutide).  I’ll provide a short list in a moment.  You’ll recognize some from their TV commercials.

The side effects of these drugs included weight loss.  Eureeka! 

With a wide open field for a new drug release, the Danish company Novo Nordisk saw the open sea and dove right in.

The drug Ozempic (from Novo Nordisk), which comes with valid warnings of increased likelihood of pancreatitis, pancreatic cancer, and thyroid cancer, and which clearly said it is not prescribed for weight loss, is re-released as the weight loss drug Wegovy.

Here’s the short list I promised:

  • Trulicity
  • Byetta
  • Victoza
  • Ozempic
  • Rybelsus
  • Mounjaro
  • Saxenda
  • (note that many practices will offer compounded semaglutide which has even few controls)

If you haven't yet read my last article on this new breed of weight loss drug, read it.

GLP1 WEIGHT LOSS DRUGS

I would never professionally tell anyone to stop using a drug (unless its someone I’m close to, love, or care about deeply and I knew the risks to be excessive), nor would I tell them not to take a drug, as that’s outside of my scope of practice.  But I can act in anyone’s best interest by providing information that adjusts their line of thought and leads them to make better decisions.  Simply understanding the history of weight loss drugs, seeing the pattern of consequence and failure, and recognizing that the drug companies have increased revenues despite side effects and death should be enough to arm you with some food for thought that you can pass along.

I’ll leave it at that and provide a few references to research studies specifically addressing the side effects of semaglutide (this is just a small sampling.  There’s an entire rabbit hole you’re free to go down as you continue to research). 

I’ll also point out that when we nutritionally guide our clients to stabilize blood sugar, they will naturally improve the balance of insulin and glucagon (without side effects) and when we integrate the strategies I alluded to earlier, and I share in my professional programs, the choice between the drug or our  offerings isn’t a choice at all.

Take ownership of your health.  Recognize your own power.  Recruit professionals with track records of happy healthy outcomes rather than jumping into the newest trend or rage (especially now, seeing the continued pattern of weight loss drug releases).

Be Better,

Phil Kaplan

The Metabolic Reboot - The Ultimate Path to Lasting Fat Loss

RESEARCH REFERENCE

Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011;141:150–156 

Butler PC, Matveyenko AV, Dry S, Bhushan A, Elashoff R. Glucagon-like peptide-1 therapy and the exocrine pancreas: innocent bystander or friendly fire? Diabetologia 2010;53:1–6 

Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM, Butler PC. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model. Diabetes 2012;61:1250–1262 

Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011;141:150–156 

Butler PC, Matveyenko AV, Dry S, Bhushan A, Elashoff R. Glucagon-like peptide-1 therapy and the exocrine pancreas: innocent bystander or friendly fire? Diabetologia 2010;53:1–6

Gier B, Matveyenko AV, Kirakossian D, Dawson D, Dry SM, Butler PC. Chronic GLP-1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model. Diabetes 2012;61:1250–1262 

Gier B, Butler PC, Lai CK, Kirakossian D, DeNicola MM, Yeh MW. Glucagon like peptide-1 receptor expression in the human thyroid glandJ Clin Endocrinol Metab 2012;97:121–131

 

 

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