Weight Loss Drugs Part 1-4 : Is Obesity a Choice?

TITLE: Could this NEW drug CURE OBESITY? The latest study results are AMAZING!


Me1: Could this NEW drug CURE OBESITY? The latest study results are AMAZING!

After decades of research, weight-loss drugs might finally be more than just a scammy infomercial

ME2: Wait, how can a pill “cure” obesity? Don’t people just need to decide to eat healthier? And less?

ME1: It’s not so simple. Back in 1994, a molecular geneticist named Jeffrey Friedman discovered that when some of his lab mice had a particular faulty gene, they kept eating until they became obese. That gene encoded for a hormone called leptin, normally produced by your fat cells to tell your brain that you’re full. I’d like to see you try to stay thin when you eat a full meal but still FEEL starving!


ME2: Yeah but how many humans can blame a faulty gene?

Me1: That was just an example. Since then, we’ve discovered all sorts of things that can go wrong with your hunger, satiety, nutrient absorption, and more. Even your gut microbiome could influence weight gain. And it’s not just one-sided; I bet you have that 1 friend that always stays thin no matter how much they seem to eat.



ME2: [start off nodding] Jill. We hate Jill.

Me1: Exactly! Just like she doesn’t stay thin based on some “act of willpower,” so too that’s often not a feasible solution for someone trying to lose weight. Many people feel this, and start searching for an external solution, which has lead to a massive industry of fad diets, weight loss supplements, and fat burning devices. But the vast majority are just snake oil preying on the desperate.

Me2: So what, we just say “love your body, your weight doesn’t matter?”

Not quite. Yes, absolutely love your body! And never look down on someone for weighing more. Or less. The whole point here is that it’s not about blame. Weight is complicated. And shouldn’t just be ignored, because CAN impact health and quality of life. But even there, the health standards and beauty standards don’t really line up.

A 2022 Meta Analysis of 35 studies found a J-shaped curve. Your risk of dying from any cause goes up at very low body fat %’s, and at high ones. The lowest risk for men isn’t here. It’s here (22%).


The lowest risk body type for women isn’t this. It’s this (35%).


Body fat % vs risk in Men
Body fat % vs risk in Men

Body fat % vs risk in Women
Body fat % vs risk in Women

And, to widen the disconnect, it really depends on the type of fat. Subcutaneous fat that sits under the skin and makes you look puffier can actually lower risk, especially as you get older. It’s the visceral fat between the organs that has real negative health impact. And that’s not really easy to spot with your eyes. Unless you were born on krypton.

Me2: Weren’t you supposed to be talking about some new discovery?

Right. I have a bad habit of getting distracted by cool research studies. [turn to camera] - if you like hearing about cool research studies that help you optimize your life and debunk misinformation, hit that follow button!

Now let’s talk obesity drugs.

Me2: Finally

Over the last century, there have been DOZENS of drugs approved to treat obesity, most of which worked by affecting neurotransmitters like serotonin, dopamine, and adrenaline, and in so doing they impacted appetite.

ME2: Wait, aren’t those neruothingies also involved in, like, a LOT of other stuff in your body?

Aye, there’s the rub. And that’s why twenty five obesity drugs have been withdrawn since 1950. Because of side effects messing with the brain and heart, as well as addiction and abuse issues.


Back in the 90’s, there was a widely prescribed weight loss drug combo called fen-phen. Sounds fun right? And i’m sure it was at first. It was a pairing of two drugs that had each been on the market for over 10 years, a sedative appetite suppressant and an amphetamine, and it was prescribed to over 6 million americans! It spawned “fen-phen mills,” where doctors would make bank buying each drug in bulk and selling them to patients. But most of its popularity was based on a study of only 121 people, with a 1-year safety followup. The drug was withdrawn in 1997 after hundreds of women taking it ended up developing heart valve problems.

ME2: Ok so no broad “messing with brain” drugs. More on the new stuff. How do they work?

Excellent question, my dear… whatever your name is.

In the 2000’s the FDA started approving some drugs that helped Type 2 Diabetics manage their blood sugar. They mimicked a hormone called GLP-1 that helped raise insulin production and lower blood glucose. Buut over time they noticed that those taking it would also lose weight, because of how GLP-1 receptors in the brain and gut also regulate appetite and digestion.


Me2: How much weight loss are we talking?

In 2016, one of these new drugs called Liraglutide was shown to help people lose an average of 18 pounds over a year- roughly 8% of their bodyweight, 5% more than the placebo.


Me2: That’s… nice I guess? Doesn’t seem too crazy

I’m getting there! Let’s fast forward to June of 2021. The FDA approves a drug called semaglutide, similar to liraglutide but it stays active for longer. The clinical trial participants that got weekly injections ended up losing 15% of their bodyweight over the first year before plateauing, compared to the 2.4% of the placebo group.


“AND THAT WOULD BE ENOUGH” - (insert clip)

Dayeinu, right?

But it doesn’t stop there!

Enter: Terzepatide

Me2: Who even comes up with these names?

I know right? And the brand names are worse. But stop distracting me!

Terzepatide was approved last year to treat Type II diabetes, but its use lead to a whopping 21% drop in body weight! Compared to a 3% placebo. That’s in the same ballpark as bariatric surgery! But without a surgeon! It targets both GLP-1 and another hormone called GIP (glucose-dependent insulinotropic polypeptide) which also affects insulin production.


And they also reduced triglyceride and LDL cholesterol, raised the good HDL cholesterol, and lowered blood pressure. All of which could just be an extension of the weight loss, but still great!

And in Type II diabetics it lowered HbA1c by ~1.6%, when most were already on metformin!


Me2: Ok but what about side effects? Didn’t we just talk about jumping to safety conclusions?

Some people do experience GI problems. Nausea, vomiting, abdominal pain, constipation and diarrhea. But only 1 in 15 found them unpleasant enough to back out of the trial. But they’re the worst when you start at a high dose. Most of the side effects were seen at the start of the trials. That’s why a slow ramp up of the dosage is going to be key.

In the over 5,000 clinical trial participants who received it, there were also 13 cases of pancreatitis, equivalent to a little over 1 per 400 years of people taking the drug.

But drug safety is all about relative risk, and the detailed FDA safety analysis–which has gotten better over the years–determined that it’s ability to LOWER risk for a ton of different health problems (long term microvascular disease risk reduction, preventing blindness, kidney failure with need for dialysis, and amputation due to neuropathy.) outstrips the potential negatives.

Oh, and in rodent studies there were some issues with thyroid tumors, but no such issues with humans so far. But if you have a family history of those… definitely talk to your doctor!

Me2: So where do i get it?

Terzepatide was approved last May to treat Type II diabetes, but not yet for weight-loss.


The second phase 3 clinical trial will wrap up in April, and the FDA has already allowed it to have a fast-tracked rolling submission. That could have it on the market being prescribed for weight-loss later this year. In the meantime you can already get semaglutide for weight loss.


And they’re both a once per week injection, as simple as injecting insulin.

Me2: Is there a catch here

looks uncertain Weeellllll

Me2: Spill it!

The list price of “Mounjaro,” the brand name of terzepatide, is $1,023.04 per fill. If you have most commercial insurance then manufacturer savings card that will have most people paying only $25 out of pocket. BUT, that won’t work with medicare or medicaid, and the full coverage is stil being determined.


Me2: Drug pricing is insane.

Agreed. But that’s it’s own video. Right now let’s focus on the good: When the Terzepatide trial results were presented this past November, they received a standing ovation. Worldwide obesity has TRIPLED since 1975. In 2016, more than 650 million were obese. In kids and adolescents, less than 1% were considered obese in 1975. Now it’s 6% of girls and 8% of boys.


There are many reasons for this, and of course diet and lifestyle factors are amazingly important, and those types of interventions should accompany ANY drug-based treatment. But just as modern life has brought people down, it’s about time that it started offering better solutions, and drugs like terzepatide have the potential to improve millions of lives. I for one am excited.

If you want to learn more about ways that science is improving our daily lives, hit that follow, and let me know down below what topic you want me to cover next.