Is the obesity epidemic about to end thanks to . . .

[torbee]

The power of modern pharmacology?

The Atlantic says maybe:

Ozempic Is About to Be Old News​

A “huge explosion” in obesity drugs is on the horizon.
By Yasmin Tayag

APRIL 4, 2023


All of a sudden, Ozempic is everywhere. The weight-loss drug that it contains, semaglutide, is a potent treatment for obesity, and Hollywood and TikTok celebrities have turned it into a sensation. In just a few months, the medication has been branded as “revolutionary” and “game-changing,” with the power to permanently alter society’s conceptions of fatness and thinness. Certainly, a drug like semaglutide could be all of those things: Never in the history of medicine has one so safely led to such dramatic weight loss in so many people.

But let’s not get ahead of ourselves. As weight-loss medications go, Ozempic is far from perfect. Though the drug has profound impacts, it requires weekly injections, a tolerance for uncomfortable side effects, and the stamina—not to mention the budget—for long-term treatment. (Ozempic has somehow become a catchall term for semaglutide but technically that product has gotten FDA sign-off only as a diabetes medication. A larger dose of semaglutide, marketed as Wegovy, has been approved for weight loss.)

Made by the Danish drugmaker Novo Nordisk, semaglutide dominates the U.S. weight-loss market right now, but its reign might be short-lived. The colossal demand for these drugs has spurred a competition in the pharmaceutical industry to develop even more potent and powerful medications. The first of them could become available as soon as this summer. For all its hype, semaglutide is the stepping stone and not the final destination of a new class of obesity drugs. Just how good they get, and how quickly, will go a long way in determining whether this pharmaceutical revolution actually meets its full promise.

In a sense, semaglutide hardly represents a major step forward in science. Diet drugs are nothing new, and even the category of pharmaceuticals that these new products belong to, called “GLP-1 agonists,” has been around for several years. These drugs mimic the hormone GLP-1 (glucagon-like peptide one) and bind to its receptor in the body. This triggers a sense of fullness associated with having just eaten, and also slows the release of food from the stomach. (It also increases insulin secretion, keeping blood sugar in check, which is why Ozempic is still intended as a diabetes drug.) Already, these pharmaceuticals have gotten better over time: A daily injection called liraglutide and sold as Saxenda, which was approved by the FDA in 2014 for obesity, leads to the loss of 5 to 10 percent of a person’s body weight in most cases. But one reason semaglutide took off in a way that liraglutide didn’t is that it can lead to weight loss of up to 20 percent. “Now you have a shot that’s once a week instead of every day, you’re making dramatic improvements, and people notice more,” Angela Fitch, the president of the Obesity Medicine Association and the chief medical officer of the obesity-care start-up Knownwell, told me.

 

[torbee]

But not everyone who takes these drugs can achieve that level of weight loss. More than 60 percent of those on Wegovy experience smaller changes, in part because the drug can’t account for the complex drivers of obesity that aren’t related to food. The next generation of drugs is reaching for more. The first leap forward is Mounjaro, known generically as tirzepatide, a diabetes drug from Eli Lilly that the FDA is expected to approve for weight loss this year. In one study, it led to 20 percent or more weight loss in up to 57 percent of people who took the highest dose; The Wall Street Journal recently called it the “King Kong” of weight-loss drugs. People on Mounjaro tend to lose more weight more quickly and generally have a “better experience” than those on Wegovy, Keith Tapper, a biotech analyst at BMO Capital Markets, told me. It’s also cheaper, though by no means cheap, at roughly $980 for the highest-dose option, he said; a dose of Wegovy costs about $1,350.
These leaps in potency are happening on the molecular level. Like semaglutide, Mounjaro mimics the effects of GLP-1, but it also hits receptors for another hormone—GIP. That leads to even more weight loss by further attenuating focus on food and potentially also increasing the activity of a fat-burning enzyme, Tapper said. So-called dual-agonist drugs “offer a step change” in both weight loss and blood-sugar control, he added.

And why stop at two receptors when so many others are involved in regulating hunger? “This area is exploding in terms of research and testing different combinations of hormones,” which are still poorly understood, Shauna Levy, a professor specializing in bariatric surgery at Tulane University School of Medicine, told me. Eli Lilly has another drug in the works that targets three receptors; one from the drugmaker Amgen works by “putting the brakes” on the GIP receptor and “putting the gas” on GLP-1’s, a company spokesperson told me. Several other companies have already joined what some have dubbed a “race” to develop the next great obesity drug, in which Lilly, Pfizer, Amgen, Structure Therapeutics, and Viking Therapeutics are expected to be the front-runners, Tapper said.

The potency of weight-less drugs is not the only factor that will determine the shape of their future trajectory. Wegovy and Mounjaro injections are tolerable for most people, but they are less convenient than a pill. Making oral versions of these drugs isn’t as easy as packing everything into a capsule, though. Semaglutide is a molecule that gets chewed up in the stomach. For this reason, the semaglutide pill Rybelsus, which is already approved for diabetes, leads to far less dramatic weight loss than its injectable kin. But drugmakers are undeterred by this complication, because a pill even more powerful than semaglutide would no doubt have many customers. In January, Pfizer’s CEO Albert Bourla said that an oral weight-loss drug “unlocks the market,” which he estimated could eventually be worth $90 billion. Pfizer doesn’t have any weight-loss drugs yet but is developing a twice-daily GLP-1 agonist pill; Eli Lilly also has an oral version in the works. Tapper expects those drugs to become available in 2026, and a similar offering from Structure Therapeutics is likely to follow the next year.

Drugmakers will also likely vie to create drugs with fewer side effects. Novo Nordisk notes that gastrointestinal issues are common with semaglutide; accounts of horrible nausea, constipation, and vomiting have proliferated online. As one actor put it to New York magazine, people on Ozempic are “shitting their brains out.” With Wegovy, more serious issues, such as pancreatitis, thyroid cancer, and kidney failure, are also possible but are considered rare. Although nothing to scoff at, side effects tend to subside with prolonged treatment and can usually be managed with help from a doctor, said both Fitch and Levy, who regularly prescribe semaglutide to patients with obesity. It’s possible, Levy added, that people experiencing really terrible effects may be getting their drugs from shady compounding pharmacies or even from other countries.

The fact that people are turning to sketchy outlets to get weight-loss drugs underscores the biggest issue with them: access. Medicare and most private insurance companies don’t cover anti-obesity drugs. (Such drugs are classified as “cosmetic” by the Centers for Medicare and Medicaid Services, and thus don’t qualify for coverage.) “I am hopeful that the price will come down with more competition,” Fitch told me. But there’s no guarantee that will happen: Competition typically makes a product cheaper over time, but research suggests that isn’t always the case in pharmaceuticals. Even if the drugs do become cheaper, they may not become cheap enough. The oral forms of these drugs, some of which could be available by 2026, are expected to cost about $500 a month, Tapper said. By 2030, the cost of obesity drugs could come down to about $350 a month, according to a recent Morgan Stanley analysis, which would still be out of reach for many Americans.

Levy estimates that the next five years will bring about a “huge explosion” of next-gen obesity drugs. In that case, the market will likely expand to accommodate a variety of drugs with different price points and efficacies. Some people may aim to lose 20 or more percent of their body weight; some may be content with less. The market is so diverse that it will likely “support a broad range of options,” said Tapper, such as cheaper, lower-dose oral drugs for people who have milder medical issues, and more expensive injectables for those with more severe medical concerns. That opens up the possibility that medically mediated weight loss could soon be an option for a far greater proportion of people.

Regardless of how much these drugs’ costs may decrease, they will always add up if people are paying out of pocket for them. They are meant to be taken long term: Once a person stops taking Wegovy, the weight tends to come right back. The current crop of weight-loss medications are essentially maintenance drugs, much like the cholesterol-busting drug Lipitor, which is taken daily to treat long-term disease. But Lipitor, unlike obesity drugs, is generally covered by insurance. Unless obesity drugs receive the same kind of coverage, no level of improvement will lead them to deliver on what Ozempic is promising us now.

 

[tarheelbybirth]

Yep, Big Pharma our way out of a fatty epidemic caused by Big ProceessedFood.

 

[binsfeldcyhawk2]

Yep, Big Pharma our way out of a fatty epidemic caused by Big ProceessedFood.

What could go wrong?

 

[torbee]

Yep, Big Pharma our way out of a fatty epidemic caused by Big ProceessedFood.

It's the American Way!

Kind of reminds me of Homer Simpson's quote about booze:

 

[Fijimn]

My sis-in-law started Ozempic for weight loss. From what I can tell, it works by making you feel so bad that you don't want to eat and what you do eat, you throw up immediately.

 

[FAUlty Gator]

Ozempic is for posers. Mountjaro is for the real playas.

My doctor told me moths ago that gastric bypass doctors are freaking out about the fact Mountjaro is about to be made for everyone. Not just Type 2 Diabetics. They're about to be put out of a lot of clientele.

 

[markfromj]

Yep, Big Pharma our way out of a fatty epidemic caused by people eating poorly.

FIFY.

 

[General Tso]

That would be phat

 

[GOHOX69]

No side effects at all... 😉

 

[Bank of Hawk]

I have a fool proof solution: good ole fashioned exercise and a proper diet.

 

[FAUlty Gator]

I have a fool proof solution: good ole fashioned exercise and a proper diet.

 

[BubsFinn]

My sis-in-law started Ozempic for weight loss. From what I can tell, it works by making you feel so bad that you don't want to eat and what you do eat, you throw up immediately.

Wouldn’t it be cheaper just to have a 15 year old girl shame you every time you wore a tight shirt?

 

[Formerly Rockymtnole]

Ozempic is for posers. Mountjaro is for the real playas.

My doctor told me moths ago that gastric bypass doctors are freaking out about the fact Mountjaro is about to be made for everyone. Not just Type 2 Diabetics. They're about to be put out of a lot of clientele.

At $980 a dose? How many can afford that out of pocket for a lifetime drug?

 

[EasyHawk]

In the 1960's many expectant mothers took Thalidomide, a wonder drug
to combat morning sickness. Then there were suddenly many births of kids
with deformed limbs. A distant relative of mine was impacted and it was
really bad, he had flippers for arms and legs. They used to prescribe amphetamines
for weight loss also in the 60's and 70's. Oh, people lost weight. Beware the next
wonder drugs.

 

[torbee]

A distant relative of mine was impacted and it was
really bad, he had flippers for arms and legs.

Bet he kicked ass in the swimming events at the Special Olympics though. So sort of a silver lining.

 

[onlyTheObvious]

At $980 a dose? How many can afford that out of pocket for a lifetime drug?

Easy way to get votes is what I am smelling.

 

[goldmom]

Yep, Big Pharma our way out of a fatty epidemic caused by Big ProceessedFood.

No kidding. Big Macs for everyone, supersize the fries and pass the Ozempic.
Ugh.

 

[HawkeyeHitman]

The best weight loss drug is getting off your ass.

 

[goldmom]

In the 1960's many expectant mothers took Thalidomide, a wonder drug
to combat morning sickness. Then there were suddenly many births of kids
with deformed limbs. A distant relative of mine was impacted and it was
really bad, he had flippers for arms and legs. They used to prescribe amphetamines
for weight loss also in the 60's and 70's. Oh, people lost weight. Beware the next
wonder drugs.

You know what was so “interesting” about the effects of Thalidomide?
A number of those babies had beautiful facial features.
I can faintly recall an article in Life Magazine (which my parents subscribed to) about an American woman traveling to a Scandinavian country to have an abortion because she had taken Thalidomide regularly. I was maybe in 4th grade and it was the first time I heard about the word abortion and what it meant.
It turned out that indeed the fetus would have been born with no arms.

 

[Finance85]

As a society, we shouldn't be trying to manage obesity with drugs. Drugs should be a last resort.

When I was diagnosed with Type II Diabetes, it was something that came on all of a sudden. When I dropped by AiC nearly in half in less than 6 months, that was aided by drugs, but the change shouldn't have been that drastic in that time frame. My doctor told me that, unfortunately, most people simple keep their same diet, and rely on drugs. I didn't want to do that. So my medication got cut and it's no longer needed. I have to be careful with my diet.

In my case, weight wasn't and isn't an issue. It more about my liver and pancreas and the amount of sugar and white carbs I was consuming.

 

[ICHawk-I]

My sis-in-law started Ozempic for weight loss. From what I can tell, it works by making you feel so bad that you don't want to eat and what you do eat, you throw up immediately.

I asked my wife, a pharmacist (no pics), why this is.

From the article:

This triggers a sense of fullness associated with having just eaten, and also slows the release of food from the stomach.

She said that those who take it probably are used to overeating. So when your stomach doesn't empty as fast as and you overeat and pile more food into it, it only has one way to go, and that's up. She said heartburn is another side effect, for the same reason.

 

[tarheelbybirth]

In the 1960's many expectant mothers took Thalidomide, a wonder drug
to combat morning sickness. Then there were suddenly many births of kids
with deformed limbs. A distant relative of mine was impacted and it was
really bad, he had flippers for arms and legs. They used to prescribe amphetamines
for weight loss also in the 60's and 70's. Oh, people lost weight. Beware the next
wonder drugs.

Thalidomide is chiral - meaning it comes in one form and it's mirror image. Thalidomide worked very well as a sedative and was also useful for insomnia, gastric issues, and nausea. It was considered so safe, that it was sold over the counter in many countries. But it hadn't been tested on pregnant women. Left-handed thalidomide is the useful enantiomer but the RH version is teratogenic - it causes profound birth defects. What was being sold was a 50/50 mix. Even if they had known and had the ability to separate the different versions, it wouldn't have mattered because the LH version gets converted in the body into both forms.

It was never approved in the US but there were about 20,000 people participating in a clinical trial and there were some doctors who had access and were providing it to patients so there were victims here but it could have been much worse.

 

[FAUlty Gator]

In the 1960's many expectant mothers took Thalidomide, a wonder drug
to combat morning sickness. Then there were suddenly many births of kids
with deformed limbs. A distant relative of mine was impacted and it was
really bad, he had flippers for arms and legs. They used to prescribe amphetamines
for weight loss also in the 60's and 70's. Oh, people lost weight. Beware the next
wonder drugs.

Children of Thalidomide!

Buddy Holly, Ben Hur, space monkey, mafia
Hula hoops, Castro, Edsel is a no-go
U2, Syngman Rhee, Payola and Kennedy
Chubby Checker, Psycho, Belgians in the Congo

 

[tarheelbybirth]

FIFY.

Highly processed foods are designed to be addictive and unfillingand it's ok to blame the choices people make but when the only place available to buy food is the Dollar General it makes it difficult to eat healthy.

The funny part is when we had a First Lady who was trying to get schools to serve healthier foods, the "conservatives" - including MANY here - went f'n BALLISTIC.

 

[3boysmom]

I've actually been following this for about 6-9 months. My husband is on Mounjaro for type 2 diabetes and it has been a godsend for him. He's not had anything major in the way of side effects and has lost about 50 pounds. His A1C has also gone down quite a bit but still has a bit to go. He has another follow up next month and hoping its in the normal range then.

I've been following both Mounjaro and Ozempic/Wegovy on Tik Tok. The one take away I have found is that it doesn't work on it's own. You have to make changes to your diet and at some point start to incorporate exercise into your day. Those things are made easier because of the lack of hunger and diminishing of food noise/cravings when taking the meds. I've also seen anecdotally that for some people it diminishes their cravings for alcohol. How amazing would it be if it can be used to help people fighting alcohol addictions as well?

It's kind of amazing to me to be on this board and watch people shout from the rooftops about how the fatties need to lose weight. A drug comes out that is really promising in helping do that and it's all "no, not like that". Do we want people to lose weight or are we just looking to punish them for being fat in the first place?

 

[Aardvark86]

The Atlantic would be wrong. Was discussing this with my sister in law, a former senior NIH endocrinologist who's actually like, a big deal in obesity research. Sure, the emerging drugs work great...as long as you're taking them. But if you stop, well, unless you've modified behavior, that weight will come right back on.

 

[torbee]

I've actually been following this for about 6-9 months. My husband is on Mounjaro for type 2 diabetes and it has been a godsend for him. He's not had anything major in the way of side effects and has lost about 50 pounds. His A1C has also gone down quite a bit but still has a bit to go. He has another follow up next month and hoping its in the normal range then.

I've been following both Mounjaro and Ozempic/Wegovy on Tik Tok. The one take away I have found is that it doesn't work on it's own. You have to make changes to your diet and at some point start to incorporate exercise into your day. Those things are made easier because of the lack of hunger and diminishing of food noise/cravings when taking the meds. I've also seen anecdotally that for some people it diminishes their cravings for alcohol. How amazing would it be if it can be used to help people fighting alcohol addictions as well?

It's kind of amazing to me to be on this board and watch people shout from the rooftops about how the fatties need to lose weight. A drug comes out that is really promising in helping do that and it's all "no, not like that". Do we want people to lose weight or are we just looking to punish them for being fat in the first place?

Great work by him (even with a little help!)

I share your astonishment that people are snarky about overweight folks helping themselves any way they can.

I started Noom on March 5 and have lost 16 pounds as of this morning. I'm actually at the weight shown on my driver's license for the first time in about 6 years, lol. I feel like this time it's going to stick (I've yo-yo'd a few times) because Noom is very psychology and mindfulness based and isn't gimmicky or easy, but rewarding.

I would not hesitate to incorporate a weight loss drug into the effort if I was struggling or my doc recommended it, however.

 

[torbee]

The Atlantic would be wrong. Was discussing this with my sister in law, a former senior NIH endocrinologist who's actually like, a big deal in obesity research. Sure, the emerging drugs work great...as long as you're taking them. But if you stop, well, unless you've modified behavior, that weight will come right back on.

So The Atlantic ISN'T wrong, then

Regardless of how much these drugs’ costs may decrease, they will always add up if people are paying out of pocket for them. They are meant to be taken long term: Once a person stops taking Wegovy, the weight tends to come right back. The current crop of weight-loss medications are essentially maintenance drugs, much like the cholesterol-busting drug Lipitor, which is taken daily to treat long-term disease.

 

[3boysmom]

The Atlantic would be wrong. Was discussing this with my sister in law, a former senior NIH endocrinologist who's actually like, a big deal in obesity research. Sure, the emerging drugs work great...as long as you're taking them. But if you stop, well, unless you've modified behavior, that weight will come right back on.

That's what many of the obesity docs are saying. Obesity is a chronic condition and may have to be treated for life. I would guess that the number of people who regain after weight loss drugs is similar to the number of people who regain after any other type of weight loss journey. You will be fighting your body's set point.

 

[unIowa]

I have a fool proof solution: good ole fashioned exercise and a proper diet.

That is the strategy of the last 30 years. Look around, it aint working.

 

[The Tradition]

I hope this works.

I was at the art festival in downtown Sanford, FL today. Fatties everywhere.

 

[unIowa]

I've actually been following this for about 6-9 months. My husband is on Mounjaro for type 2 diabetes and it has been a godsend for him. He's not had anything major in the way of side effects and has lost about 50 pounds. His A1C has also gone down quite a bit but still has a bit to go. He has another follow up next month and hoping its in the normal range then.

I've been following both Mounjaro and Ozempic/Wegovy on Tik Tok. The one take away I have found is that it doesn't work on it's own. You have to make changes to your diet and at some point start to incorporate exercise into your day. Those things are made easier because of the lack of hunger and diminishing of food noise/cravings when taking the meds. I've also seen anecdotally that for some people it diminishes their cravings for alcohol. How amazing would it be if it can be used to help people fighting alcohol addictions as well?

It's kind of amazing to me to be on this board and watch people shout from the rooftops about how the fatties need to lose weight. A drug comes out that is really promising in helping do that and it's all "no, not like that". Do we want people to lose weight or are we just looking to punish them for being fat in the first place?

The reason why these drugs work for obesity is because insulin resistant caused obesity is essentially the same thing as diabetes, just at an earlier stage before your pancreas starts to putter out and can't pump out as much insulin. So those who uses these drugs for weight managment are essentially treating early onset diabetes. These folks suffer with high fasting insulin which leads to chronic inflamation, added weight, and very poor health outcomes. When the disease progresses two things happen, cells stop reacting to insulins signaling and/or the pancreas can no longer produce enough insulin to keep glucose pumping out of the blood and into the cells. Eat less and move more, yes, but the underlying biology needs to be corrected for that to be effective. Our medical definition of diabetes likely should be changed to earlier diagnosis and fasting insulin should become a standard lab pulled from metabolic pannels. This would catch the disease in its earlier stages so treatments and eating strategies can be put into place sooner which should lead to better health outcomes and less strain on our medical system via diabetes and obesity. The weight is a symptom of the underlying metabolic disfunction, not the other way around.

Upon seeing Lilly's trial data last summer I plowed $20k into their stock, it has been a good choice and they have even better meds on the way in a few years that are in earlier trials than mounjaro. Mounjaro could be the best selling medicine of all time as it combats the very food enviroment that is driving the nations obesity issues. Amgen has been relatively flat but I put $10k in there after seeing their phase 1 trial data on their longer lasting dual acting obesity med. Theirs is a once a month shot that uses antibodies to deliver the medicine over longer periods (or something like that) and the trial data is showing to be a bit better their Lillys Mounjaro. It's GIP action takes the opposite approach that Lilly took with Mounjaro (from my understanding, I am not a scientist), if the saftery profile lines up similar to these other incretins then they will have a huge winner on their hands as well. The share price for Amgen is a bit down the last few months so a good time to jump in IMO.

 

[noleclone2]

Meth has been available for decades and works faster.

 

[unIowa]

The Atlantic would be wrong. Was discussing this with my sister in law, a former senior NIH endocrinologist who's actually like, a big deal in obesity research. Sure, the emerging drugs work great...as long as you're taking them. But if you stop, well, unless you've modified behavior, that weight will come right back on.

Yes...just like if someone stops taking their HBP meds their blood pressure goes back up. What this should signal to the public is that obesity is a disease of underlying metabolic disfunction and our food enviroment exploits that disfunction further compounding the issue.

Also, if someone stops diet and exercise they loose those gains. If someone stops taking their anxiety meds, the anxiety returns. And on and on.

For these medicines to be accepted more readily by insurers there will need to be a lower cost maintenance plan in place for when someones disease is controlled. For some I am guessing their new habits will be enough but that will likely be very few. Historical studies show that about 4% of people who lose a significant amount of weight are able to keep it off longer than 2 years, that means diet and exercise has a 96% failure rate as well so the "if they stop taking it they will gain the weight back..." arguement doesn't hold much water bc that argument can be made of any weight loss protocols.

Look at what happened to the people on The Biggest Loser, almost all of them gained all the weight back and then some. Starving yourself and exercising 8 hours a day (which is what those people had to do) absolutely destroyed their basal metabolic rates, it broke them biologically to the point most ended up worse off.

 

[unIowa]

Meth has been available for decades and works faster.

Yes...you get to lose weight and all sense of self worth and pupose. Its also way cheaper! 😆

 

[Bank of Hawk]

Humans evolved over millions of years to eat a certain type of diet and be physically active. For most of human history, we were hunters and gatherers who foraged and moved around, just to survive to the next day. Our bodies are adapted to this type of lifestyle, which included regular physical activity and a diet rich in whole, unprocessed foods. So the extremely recent change in both of those, is also to blame. Notwithstanding that better weight loss drugs and advances in other similar drugs, isn’t a potential solution.