Data from about 200,000 participants. New GLP-1 users compared against new SGLT-2i/DPP-4/sulfonylurea users :
“Compared to usual care, GLP-1RA use was associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions. There was an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis and drug-induced pancreatitis associated with GLP-1RA use compared to usual care.”
It’s already generating nearly 40% of revenue for major drug companies like Eli Lilly.
It’s projected to generate $126B in sales by 2029.
GLP-1 drugs (like Ozempic and Mounjaro) are a case study in what’s possible when you tackle giant markets that people truly care about. It’s an example of how targeting the root cause of diseases keeps people healthier for longer. It’s an example of our larger thesis of moving from sick care to healthcare.
GLP-1s drugs are a blueprint for the next era of medicine. I can tell you this as an investor who has followed these technologies. And as a person, who started taking these drugs about a month or two ago.
This is just the beginning.
A few years ago, people saw being overweight or obese as a personal failing. That was never 100% true — there is a genetic component to obesity for example. But back then, the idea of taking a drug to magically lose weight seemed crazy.
People say the same about aging. If you ask people if they want to live longer, many initially say no. But if you ask them if they want to feel young, feel healthier, watch their great-grandchildren grow up…that answer changes.
This has been my feeling more and more those last few months : if we’re talking about longevity and not talking about GLP1 agonists, then we’re wasting time.
At the highest dose, retatrutide works like a statin by slashing ldl levels by 40%. It also actually increases egfr, beating the SGLT2 inhibitors in efficacy. And because of the glucagon agonism, subjects are in perpetual ketosis at the highest doses , even after consuming carbs. That’s in top of the cardio benefits, which even an older drug like semaglutide provides.
I am stacking Mounjaro and Dapaliflozin and love the results. Only issue was a pre-employment drug test where they told me I was diabetic because there was glucose in my urine. I just played dumb and said “Ok, I will follow up with my doctor.”
And it may delay osteoarthritis, which is my personal aging nightmare. The pain in my hands in my early sixties, despite 3 years of râpa is alarming. Am interested in @Steve_Combi response to this paper especially since it seems counter to the osteo results @RapAdmin posted above.
Osteoarthritis treatment via the GLP-1–mediated gut-joint axis targets intestinal FXR signaling
Osteoarthritis is a common degenerative condition of the joints that is usually attributed to “wear and tear” and is managed by treating the symptoms. By performing metabolomic studies in hundreds of patients from independent clinical cohorts, Yang et al . identified specific differences in bile acids between people who did or did not have osteoarthritis (see the Perspective by Liu), identified the underlying signaling mechanism, and also linked the differences in bile acids to specific species among the intestinal microbiota. Using a mouse model of osteoarthritis, the authors demonstrated the effectiveness of repurposing a clinically approved drug that targets bile acid metabolism. Moreover, human patients using this drug for other reasons had a lower risk of requiring a knee replacement for osteoarthritis, providing further support for potential clinical translation. —Yevgeniya Nusinovich
That has been on my mind for a while now. My recent ancestors, father, and his father had osteo and my grandfather was quite bent over from it in his 70’s and got worse until he passed at 96. My father was getting bent over from it as well but passed at 75 from an auto accident.
As I approach 70, I’m in much better shape osteo wise than they were.
I have it in my left little finger and had an x-ray of that hand a month ago. It’s in 2 joints and I’ve lost probably 30% of the flex in that one finger. All the other joints in that hand are clear. So I’m hopeful
I’ve been taking GLP1-RA’s for 20 months now. I’ll be tracking my osteo for the next few years but who knows.
BUT what really works for me is Nattokinase. If I miss it for 1 day, I can feel pain in that finger the next day. It only takes one more day to really notice it. Fortunately getting back to my daily dose resolves the pain within 24 hours. The key to this one is like most things, correct dose.
I posted a study on the effective dose some where on the forum, and it’s quite high. The dose is measured in FU’s (fibrinolytic units). In the study it indicated anything under 8,000 FU’s was not beneficial. The one I use is 5,000 FU’s per gm. I take 10,000 FU’s daily. That’s about 2gm of the product I use. Every source of Nattokinase will have an FU to mg rating so that is an important measure to take into consideration. There are contraindications for Nattokinase so be aware of that.
Thanks, dang had hoped your GLP1 routine would make additional supplements unnecessary. Mine is in both basal thumb joints so high impact on doing almost everything.
I’m interested in trying glp1 micro dosing but getting peptides in Canada seems tricky. Do you have a preferred Nattokinase product available in Canada, Or dm? Thanks
This powder is pretty innocuous, no bad flavour. I have this in my super shake every morning. But when I skip my shake I just put it in water and stir it up and drink it down.
I have a cast iron constitution (as they say), not much bothers my gut but this stuff is not difficult to consume anyway.
I was under the impression that proteolytic enzymes need to be taken on an empty stomach, otherwise they just get wasted on digesting proteins in the stomach contents(?).
I’d hate for you to be wasting it in the smoothies, but I guess if you’re buying it in bulk you’ve got plenty to spare.
I have not done that since I started taking Nattokinase 4 years ago. I think you do bring up a valid point but I have not seen definitive clinical info on either side of this. Mostly speculative commentary based on the “proteolytic” aspect. It does appear to be sensitive to high gastric acid so an empty stomach first thing in the morning has the highest levels of gastric acid…
When people eat Natto as part of their diet, I doubt it’s on an empty stomach and probably part of a meal with more to it than just the natto.?? where benefits have been evaluated in population studies,
This is the study I referenced previously and I can’t see if they used it with or without food. It’s benefits do seem to be very dose dependent which may reflect the consumption protocol.
This is likely impossible to distinguish given that there’s always dramatic weight loss in the published studies. Since incretins don’t have any direct effect on lipids it has to be the loss of liver fat that does it (thus no effect on lipids if visceral fat is already low).
It may be indeed due to dramatic decreases in liver fat, here are several graphs detailing it:
average liver fqat reduction of 50% after 48 weeks on those on 1mg and up
liver fat reduction of 30% were achieved by at least 71% of patients, reduction of >50% was achieved by at least 43%, liver fat reduction of >70% by at least 22% of patients. 80% of patients on the highest dose achieved liver fat reduction of >70%
by week 24, at least 27% had a liver fat content of <5%
Interesting, I’ve heard that the body protects the liver with increases in saturated fat intake by dumping LDL-C into the blood stream, which is why serum LDL-C increases with saturated fats. I don’t know how true this is. But SFA intake is related to liver fat, and LDL-C.
