Part 1 of 3 {I think}
Happy Anniversary:
Today is the one-year anniversary of my first Zepbound injection. Fifty-two weeks later I am 68 pounds lighter as well as two shirt-sizes and three jean-sizes smaller. That represents an almost 24% loss from my starting weight. One fourth of me is gone. This puts me above average for people taking Zepbound (per published studies).
My wife started nearly a year before me. She has reached her target weight with a total loss of 105 pounds (at almost the 2-year mark now) which puts her loss at just over 37% of her starting weight. Well more than a third of her is gone. She has far exceeded the average.
It is safe to say, this drug is important to the two us.
The story to be told:
I mentioned last fall that I had started an article on the new class of weight loss drugs. It is a topic that seems to pop up on Glibs somewhat regularly. I started out just expecting to cover what the new drugs are, how they work, the exploding market in these drugs, and the ongoing competition between the two leading suppliers: Novo Nordisk (the manufacturer of Ozempic/Wegovy) and Eli Lilly (the manufacturer of (Mounjaro/Zepbound).
But I soon realized that I would need to dive into my personal experiences to explain the reasons these drugs (or at least Zepbound) have become invaluable to my wife and me. However, I am allergic to disclosing personal information in public forums, so I have been putting this off close to half a year.
Fair warning:
I need to make it clear that I am not a neutral observer on this topic.
Also, I have decided the only path to get past my discomfort with posting about my personal experiences is to bury the whole topic under a mountain of snark. I will be starting with information that is easily acquired from public sources then layering on various unsupportable claims and conspiracy theories as well as a considerable amount of sarcasm and cynicism. Treat everything that I write here with extreme suspicion and do your own due diligence.
Note that I will, however, endeavor to be truthful about my own actual experiences.
Oh yeah – AI-based search and copy/pasta is likely to show up throughout this series of articles
Money Printer go BRRRRRR:
Diabetes is good for business. It can’t be cured, but it can be managed. And “management” means selling drugs to customers for life. It’s like printing money.
Ozempic (semaglutide) from Novo Nordisk is first approved in December 2017 for the treatment of Type 2 diabetes. It is expected that patients will stay on Ozempic for life (ka-ching). However, the story is not over yet. An unexpected side effect of Ozempic is significant weight loss (which was observed during the original clinical trials).
Note this is perhaps the greatest unexpected benefit of a new medicine since the observation that an oral hypertension medicine causes people to grow hair.
This leads Novo Nordisk to conduct additional research thus kicking-starting the development of Wegovy (a higher-dose version of semaglutide). Wegovy is approved for chronic weight management in June 2021.
In 2021, Novo Nordisk essentially creates a new market. Money is flooding in. Three years later, Novo Nordisk is raking in $48.6 billion in annual revenue and has achieved a market capitalization exceeding $500 billion.
Money attracts attention; lots of money attracts competition.
Mounjaro (tirzepatide) from Eli Lilly is first approved May 2022 for the treatment of Type 2 diabetes. Eli Lilly is 5 years late to the party. But Zepbound (tirzepatide) hits the market for the treatment of obesity only a year and a half later in November, 2023.
Note: Unlike Ozempic and Wegovy, Mounjaro and Zepbound contain the exact same active ingredient at the exact same dosage. But they are FDA-approved for different medical conditions and differ primarily in insurance coverage.
Zepbound provides much better weight loss in trials (average of 20.2% for Zepbound compared to 13.7% for Wegovy). Eli Lilly starts to steal business away from Novo Nordisk. The money is not bad – $4.16 billion in U.S. revenue from Zepbound in the first quarter of 2026, marking an 80% increase from the same period the previous year.
Novo Nordisk responds by getting approval of an oral version of Wegovy. People can take a pill once a day instead of sticking a needle in their belly every week. Note that the market for injectables is limited to the number of people willing to stick them themselves every week for the rest of their life. But by now, everyone in America is conditioned to take a pill for any problem they may have.
Trials show the pill is just as effective as the shot. Sales surge.
However, Eli Lilly is looking to up the ante with a new medicine – retatrutide – which has recently cleared a pivotal Phase 3 trial. As a triple hormone receptor agonist targeting GIP, GLP-1, and glucagon, retatrutide produced dramatic results: patients lost an average of 28.3% of their body weight (approx. 70.3 lbs) over 80 weeks, with extension data showing up to 30.3% loss (approx. 85 lbs) at 104 weeks.
Copy/Pasta Warning – skip to the end if you’re not interested.
The drugs:
- Semaglutide is a GLP-1 agonist
- Tirzepatide is both a GLP-1 and GIP agonist
- The future retatrutide will have a GLP-1, a GIP, and a Glucagon agonist
What they do:
GLP-1 agonists (glucagon-like peptide-1 receptor agonists) are a class of medications that mimic the natural GLP-1 hormone to treat type 2 diabetes and obesity. They work by activating GLP-1 receptors in the pancreas, brain, and gastrointestinal tract to lower blood sugar and promote weight loss.
The mechanism of action involves several key physiological effects:
- Insulin and Glucagon Regulation: They stimulate the pancreas to release insulin and suppress the liver’s release of glucagon only when blood sugar levels are high, reducing the risk of hypoglycemia.
- Appetite and Satiety: By acting on the brain’s hypothalamus, these drugs reduce hunger, increase feelings of fullness, and decrease food cravings.
- Delayed Gastric Emptying: They slow down how quickly food leaves the stomach, which helps regulate post-meal blood sugar spikes and extends the sensation of satiety.
While effective, they frequently cause transient gastrointestinal side effects such as nausea, vomiting, and constipation.
GIP agonists are medications that mimic glucose-dependent insulinotropic polypeptide (GIP), a natural gut hormone released after eating to help regulate blood sugar and appetite. They work by binding to GIP receptors on pancreatic beta cells, triggering glucose-dependent insulin secretion only when blood sugar levels are elevated, which minimizes the risk of hypoglycemia.
These agonists also reduce glucagon release (a hormone that raises blood sugar) and may slow gastric emptying, helping patients feel fuller for longer. Common side effects include nausea, vomiting, diarrhea, and constipation.
Glucagon receptor agonists are a class of drugs under development for treating obesity, non-alcoholic fatty liver disease, and congenital hyperinsulinism. They function by mimicking the hormone glucagon, which generally opposes insulin by increasing blood glucose through glycogen breakdown and glucose production in the liver, while also promoting the breakdown of lipids and amino acids.
In healthy individuals, low doses of these agonists increase energy expenditure and reduce energy intake without causing hyperglycemia. Because glucagon levels are often elevated in type 2 diabetes, some research focuses on combining glucagon agonists with other incretin analogs, such as GLP-1 receptor agonists, to enhance weight loss and metabolic improvements while minimizing adverse effects like high blood sugar and increased heart rate.
Why are they better (if they’re better):
Compared to older weight loss medications, Zepbound and Wegovy are significantly more effective, offering average weight loss of 20% and 15% respectively, whereas past treatments typically yielded only 5% to 10% loss.
- Superior Efficacy and Mechanism
- Older pharmacological options worked by blocking fat absorption in the gut, limiting weight loss potential and causing gastrointestinal distress like oily stools. Older stimulants suppressed appetite but carried high risks of addiction, increased heart rate, and anxiety, with limited long-term efficacy. In contrast, Zepbound and Wegovy mimic natural gut hormones (GLP-1 and GIP) to regulate appetite and blood sugar, resulting in dramatically higher weight loss percentages without the stimulant-related cardiovascular risks or addiction potential.
- Safety and Long-Term Management
- Previous treatments often lacked robust data on long-term cardiovascular benefits or metabolic health improvements beyond weight reduction. While older drugs were often prescribed for short-term use due to side effects or tolerance, these newer GLP-1 and dual-agonist therapies are designed for chronic weight management, addressing obesity as a long-term medical condition rather than a temporary weight issue.
Catch you later: Same Bat-time! Same Bat-channel!
The next two articles will focus more closely on my personal experiences leading up to the choice to medicate for essentially forever to deal with my weight and results that I have been getting.
Note that any discussion of the massive joint conspiracies between Big Ag and Big Pharma to make people fat and then make them less fat is a long way off in the distant future.
Note this is perhaps the greatest unexpected benefit of a new medicine since the observation that an oral hypertension medicine causes people to grow hair.
Was that before or after the angina medicine that caused men to get hard-ons?
I don’t actually know
Don’t combine them.
Ask your doctor.
In the rare case an erection lasts longer than 24 hours, call a friend and brag about it.
Congrats on the weight loss.
thanks
*sings “He’s a quarter of the man he used to be.”*
https://www.youtube.com/watch?v=ADAVis_d3w4
Impressive!
Wait. Reverse that.
He’s 3/4 the man he used to be.
I iz an enginerd. I can math gud.
No anal seepage then.
none
I remember back in the day (probably the 90s) when potato chip companies starting using some fat alternative that caused anal leakage.
They didn’t last long.
Ah, Olestra.
Olestra.
Quick draw Ted.
Bonus was they had to add all sorts of vitamins to it because the increased GI motility didn’t give the gut enough time to process it from the food you were eating.
Sean’s avatar describes how I feel about beating him to the punch….
LOL yuck
I gently encouraged my wife to taking Zepbound. It helped that she wasn’t happy with her blood work.
The good news for me is it’s reduced her snoring by like 80%. Bad news for her has been the moderate nausea. Oddly for her usually several days before her next shot. Most people have the reverse issue – nausea after the shot.
Both my wife and I have been lucky with minimal nausea. It happens, particularly right after an increase in dosage.
Good to hear, Kinnath, looking forward to seeing the New Kinnaths at HH. Or any other time. Same for any Glibs
How’s your muscle mass, joint health, and general body composition?
Get a (chat) room.
It’s a serious question.
I have a larger appetite then is probably good for me (metabolically I need about 2400 kcal/day (on non-workout days), and that usually still leaves me feeling hungry in the evenings, even when I get plenty of protein (I average ~170g/day) and fat.
But…while losing a couple of pounds would be great, I’m not willing to sacrifice what little muscle I’ve managed to put on, or my general metabolic health.
So, yeah.
As every, I end up linking to Nick Norwitz on health-related posts;
I’ve just skimmed this one so far but seems relevant:
https://staycuriousmetabolism.substack.com/p/this-new-study-changed-my-mind-on
Lose 70 lbs. Some of that will be muscle.
To start with, your legs and core muscles are no longer lifting and moving 70 lbs throughout the day. If you don’t intentionally exercise, those muscles will atrophy.
The meds do not change your eating habits dramatically (discussed at length in the coming part 3). If you had a shitty diet low in protein, then you are fucked when you eat even less protein every day. At some point, you have start paying attention to getting the right nutriets.
My low back and knees have been fucked by obesity and gravity for 50 years. Weight loss did not make anything worse.
Exercises what was difficult or impossible to do before (can you say “plank”) become possible now. You need to commit to doing the work.
I will point out that I am not weaker than I was a year ago. I still walk a mile to a mile and a half at lunch during the week. And I feel better afterwards. I still move 44 lbs bags of water softener salt without problems. Basic lifting capability has changed much.
But it was odd during the first eight months or so that I could lose 40 lbs and stairs still wore me out. You lift less and less weight up the stairs every day and the body says “cool, I don’t need all this muscle anymore”.
So, now I do chair squats (protecting my back and knees), and I am up to a pair of 30-lb dumbbells. Still not quite lifting as much weight out of chair as a year ago. But a year ago I couldn’t do 3 sets of 10 chair squats without something to hold on to.
My question since day one for these GLP-1 drugs (aside from the long term side effects) has been whether this is a superficial fix to a deeper issue. If you drop 50lbs but you’re still eating McDoubles every day, are you actually more healthy, or did you just get a chemical version of liposuction?
They significantly decrease the appetite and they slow gastric emptying.
They won’t change what you eat, you’ll just get a hamburger and small fry with the obligatory Diet Coke. ( No relationship between diet soda and unsatisfied cravings, right?)
At least in my wife’s case she generally eats a balanced diet, but too much of it. This lets her reduce the portion size without being miserable.
I think, metabolically, you’re going to be more healthy. Glucose control and hence insulin control is improved on these drugs. Chronically elevated insulin is the underlying root cause of so many seemingly unrelated conditions that simply fixing, or at least mitigating, that is going to lead to better overall health.
And, at least for the glucagon agonists, there is a significantly higher impact on fatty liver (partially related to that insulin control) which is just a complete win.
Share your concerns about long term side effects (not the least of which is going to be pocketbooks); there is just no data on what’s going to happen from long term use. One can maybe find re-assurance in that these drugs mimic directly natural processes in the body; but that does not guarantee any long term safety. After all, insulin is completely natural, but dosing exogenous insulin for the long term is not good for you (modulo type I diabetic). Complex systems don’t always react the way we think they will…
I think of it from a harm-reduction standpoint; if it’s
1. Take the drugs
2. Stay morbidly obese
I strongly suspect #1 > #2, even if we’re looking at long-term effects down the road. The long term effect of being extremely overweight is an early grave.
Ideally it’d be “lose the weight without the drugs”, but that’s easier said than done for many.
We’ll see…
did you just get a chemical version of liposuction?
A preview of parts 2 and 3.
Zepbound, for me anyway, has produced dramatic changes in behavior. I still eat pretty much the same thing, but I eat much less than I used to. My daily diet wasn’t terrible before, it was mostly the excursion from the daily routine that got me into trouble. Net result is eating less of everything and there are fewer excursions trending to zero excursions.
Congrats on the weight loss. I know others who have done the same using those drugs. And it seems that the glucagon agonist class of drugs are even more effective with the glucagon aspect dominating the benefit.
It can’t be cured, but it can be managed.
I will strongly disagree with this statement, at least with respect to type II. If your macros and style of eating continuously keep your insulin elevated and you want to continue that lifestyle, you can call the result – type II diabetes – uncurable. But that’s a little bit like saying that a broken nose is incurable because you keep punching yourself in the face. If you stop the stimulus, the disease goes away.
Look forward to the remaining articles, especially wrt to side effects.
I believe the lean mass loss may have been slightly exaggerated and with any weight loss of that magnitude no matter the cause, you’re probably going to loss some lean mass; wonder if you’ve experienced any of that or have engaged in some resistance exercise regimes to combat it.
Also, AIUI, the delayed gastric emptying can lead to bowel discomfort and, in rare cases, life threatening issues. Any experience of that? The bowel discomfort, not the death.
It seems that you intend to use the treatment forever. I know some researchers that have been pre-disposed to dismissing these classes of drugs have acknowledged their value, but more as an aid in transitioning to better eating habits for long term rather than using them forever. Have you noticed anything like that in your use? Or have you pretty much just continued your food lifestyle (type of food, eating ‘schedule’, etc)?
I will strongly disagree with this statement, . .
Thank god someone called me out on my snark.
I knew this one would get caught by someone.
Speaking of anecdotal contributions, I have, every morning for the past few months, been drinking a concoction composed among other things of citrus juice and apple cider vinegar. I have not lost a single pound, which concerns me not in the slightest, but I can now say there has been a discernible reduction in belly fat, and my pants fit a bit looser. I don’t know about the magical fat burning properties, but there is a marked suppression of appetite.
*I have been using ruby red grapefruit juice, but am switching over to lemonade. It tastes a little bit better, and frozen contrate is cheaper and I won’t have plastic jugs to dispose of
*based in large part on this guy, who showed up in my youtube recommendations. Lots of nutrition stuff, which, to be honest, I allow to go in one ear and out the other, but he has a lot of interesting things to say.
*if I would increase my level of activity, instead of sitting on my ass in front of this computerbox, I would undoubtedly see even better results
I could use to lose 25ish of your american pounds. I do not trust the drugs to do it.
How do these mix with whisky?
more as an aid in transitioning to better eating habits for long term rather than using them forever.
That was my assumption. Maybe it’s pure projection, but I thought it was more to kickstart the process than a permanent solution.
As I understand it, once you hit your target weight, you start backing off the dosage until you get to a dose that can maintain your weight. Some people manage to get off the meds. But most people that completely stop the medicine regain some of the weight.
So, the big risk is to have a major weight loss (both fat and muscle); then quit the meds and regain only fat.
OT – after 6 months of radio silence but with international attention including Elon Musk on X suddenly the UK police are sorry.
https://www.telegraph.co.uk/news/2026/05/28/sorry-treating-dying-stab-victim-racist-hampshire-police/
Good news. They continue to investigate!
Yes, the UK police are indeed sorry.
I don’t think I’ve ever seen a sorrier bunch of fuckups. They should be apologizing to every tree they pass by for wasting the oxygen that it produces.
I hope they put on their universal precautions before they cuffed the guy bleeding out!
Paywalled
Turn off JavaScript.
And then there’s this
“Early-season heatwaves are especially hazardous because our bodies have not had time to acclimatize,” said Garyfallos Konstantinoudis, an environmental epidemiologist at Imperial College London, who estimates an extra 250 heat-related deaths will have occurred in England and Wales between Saturday and Monday.
SCIENCE!
It’s astounding this feeble derelict species ever survived.
Back from the meeting. Now I can respond to several interesting comments.
Peter Thorne, a climate scientist at Maynooth University in Ireland, said: “We know beyond a shadow of a doubt” that the climate crisis had made heatwaves such as the latest one stronger and more likely. “But nevertheless, many of the records being set, particularly in the UK and France, are mind-bogglingly crazy.”
“This latest heatwave in Europe is a brutal reminder of the spiraling impacts of the climate crisis, both human and economic,” Simon Stiell, UN Climate Change Executive Secretary. “The main culprit is the world’s addiction to burning coal, oil and gas, and destroying forests. Many other parts of the world are also getting hit hard, such as India and other parts of Asia. The science is clear that human-induced climate change is making these heatwaves more frequent and extreme.”
Irrefutable, according to my model.
Half the country teetering on the brink of starvation
The Brookings affordability report found nearly 38 million households would be able to get by if workers’ wages rose by $10 per hour. But that’s a tall order in a nation where the federal minimum wage has been frozen at $7.25 an hour since 2009.
“It’s dramatic, in the sense that we’re not doing that,” Perry said. “But can we do it? Yes.”
You never saw any fat people in Depression era Appalachia.