David W (aka Flex NP)
@rnflex
Jack of all trades nurse practitioner, trail runner photographer, coonhound rescuer, lover of glucagon agonism in the liver, kidney and pancreas, fascinated by obesity medicine, retatrutide fan boy, thoughts my own not my employers
But more than anything missing a dose or two 1.) reduces plasma concentration just enough to lower side effects but 2.) there's plenty to cause weight loss (I'm looking at graph C) This also means cash paying patients can extend their supply since refills are required only every 45 days.
In the real world there are other things. Like this nugget that creating a less acidic stomach environment with a PPI may also increase plasma concentration. These are things you don't see with injection as it bypasses the stomach.
The reasons are multiple. It's still semaglutide so it has a 7 day halflife but ALSO the absorption characteristics are super variable. How long you fast after a dose and even how much water you drink with the pill matter! Here's the graph from Novo:
If he had sought medical care when it was suggested to him, he at least would have had a fighting chance.
Midwest summer fish fry? Yeah. Time to feast! Walleye and yellow perch! Roasted smashed potatoes and more
37 dollars for 5 pounds of porterhouse steaks. That's about $7.50/lb. Maybe if they were priced reasonably to begin with...
They apparently decided to include a large batch(21%) of GLP1 patients who either never filled their script or took it for a month. Vast majority never even reached a therapeutic dose
Bad science paper of the day goes here. Demographics are a mess. Completely disparate groups. GLP1 group was much older. GLP1 group far more diabetic(16% vs 6%!!) different racial demographics and different rates of HTN/HLD And it gets worse from there...
Well looks like AI has started using my blog as a resource as I got a new subscriber referral from ChatGPT. Not sure whether that's a good sign or not!
Had to rush home because of bad storms took out power in our neighborhood, trees and branches and live power lines just a block from our house 🙈🙈🫠🫠 thank goodness for generators.
Bacon Mac and cheese and coconut Brown Ale after 11 humid trail miles!
Flat iron steak, 13 bucks for 1.1lbs! A steal! Twice roasted potatoes. Citrus hopslam. A great dinner. 15 month old ate an ounce of steak. 4 year old ate 4 ounces of steak. Me and wife split the remaining ~12 ounces. A great summer dinner after the splash pad today.
Even deeper cut? Every biomarker associated with changes in insulin sensitivity improved(adiponectin & IGFBP-2) or dropped(HOMA-IR, FGF21) Truly seems as if modulating glucagon is like pressing a giant reset button on your metabolism.
Incretin deep cut, what does glucagon agonism add to pancreas function? 85% drop in endogenous glucagon. Up to 50% drop in insulin. 11% reduction in glucose in NON-diabetics. I'll write up a longer blog on this later this year but these are better than anything FDA approved at the moment
I mean for orforglipron it's really dramatic. If you don't have high blood pressure it doesn't do much at all. But if you have existing hypertension. It's dropping BP by 14-16mmHg, that's as good as most ARB/ACEi drugs which are the current gold standard for blood pressure reduction.
Nearly 3 years of persistent GLP1 use and my post dinner glucose spike was...88mg/dl Pretty cool to see. At the ADA conference they were giving away free CGMs so I figured why not try it out. FYI that spike at 1600 was 97mg/dl Technology is awesome.
So the Retatrutide early access program for patients seems very real. I reached out to Eli Lilly about it last week for a few patients I thought might be good candidates. They called back today for more info. @proptermalone.bsky.social @notdred.bsky.social
Jesus H if trump is on retatrutide we'll know in a 6 months when he loses 25% of his body weight. But also...this would explain why this exists on clin trials .gov As potent as Reta is....it's not going to reverse pulmonary hypertension but that would certainly explain all the swelling...
Northern Michigan trail running is seriously undefeated. Utterly perfect weather this morning to get 8 miles in.
Mango peach vanilla galette with lime vest in the filling and crust to celebrate Fathers Days in a tropical way with the family.
Back when I was in the Reta trial my glucose was so tight you could barely tell when I ate and even after meals barely would have excursions above 100. The insulin sensitivity was off the charts
Huzzah. Data in rats shows significant extra weight loss combining the two meds(dark red squares!) good luck! Fingers crossed for you!
It appears Eli Lilly has applied for permission to enable single patient access to retatrutide on a per case basis prior to full FDA approval of retatrutide. Normally this is reserved for cancer or other rare or difficult to treat diseases. So WTH is Eli Lilly doing with this unprecedented step?
For knee arthritis patients...70% reduction in pain. For sleep apnea 60% reduction in apnea- hypopnea index 1/3 of patients reverted to a normal BMI. 2/3 reduced BMI to less than 30. Average starting BMI was 40. >10 point reduction in BMI!! Just incredible unprecedented results.
I shared this yesterday but for context. It lowers BP like a dedicated BP med. Reduces triglycerides like a fibrate drug, reduces cholesterol like a low dose statin or Zetia. Reduces hsCRP better than statins and reverses pre-diabetes better than metformin. ONE DRUG DOES THIS.
Even after 80 weeks 85% of patients lost at least 15% of their body weight. Nearly half had lost 30% and 1 in 4 lost 35% !!!! Even the 4mg arm lost 19% of their body weight with one dose titration and a quarter of those patients lost >25% of their body weight!
Yesterday the trial I was in for retatrutide showed a remarkable thing. 30% average weight loss over 104 weeks for the first time in a MEDICATION. This is medical history in the making.