Yeah I'm so excited for this drug on a personal and professional level....but the moral and ethical implications of insurance blocking access to what is probably going to be one of the most revolutionary medications ever is depressing AF.
One thing being on the primary care side is a lot of folks STILL don't get enough fiber to the point that I'm consistently recommending Miralax or Metamucil on a daily basis depending on their stool complaints. The online trend, of course, goes over the top with it. Makes your head spin.
Bringing that back to the phase 3 data, we may be on the cusp of seeing some truly remarkable lipid reductions in the phase 3 data, equivalent to moderate dose statin therapy.
Now add in 30% weight loss and what do we think that does for your risk of dying from cardiovascular disease?? /End
So I think the case is fairly clear that there's a mechanistic reason for these lipid reductions on retatrutide. What's even MORE compelling to me is that many of these reductions had NOT plateaued at 48 weeks. These lipid reductions were still happening!
There's yet ANOTHER way to see this isn't just weight loss. Because you're removing remnant cholesterol early on, that means it can't form small dense LDL cholesterol particles which are particularly good at causing arterial inflammation.
And what do we see? Reductions in small LDL particles.
So reductions in ApoC3 and ANGPTL3/8 are allowing systemic clearance of these highly atherogenic particles, while reductions in ANGPTL4/8 reduce your body's ability to *store* lipids. This should mean a reduction in ApoB as well.
And yep.
(And that's a statin-esque ApoB reduction!)
And these graphics are mostly from published data showing the ANGPTL3/8 and ApoC3 reductions mirror the triglycerides, LDL and TRL reductions. But there's a reason this is happening. Look at ANGPTL4/8, that's responsible for storing triglycerides in fat cells. It drops too.
Broadly oversimplifying here but blocking both things reduce triglycerides, but ANGPTL 3/8 reduces LDL cholesterol and ApoC3 reduces TRL-C(Triglyceride rich lipoprotein cholesterol) or "remnant cholesterol" too
That's visualized in these slides.
Both LDL and TRL are considered highly atherogenic.
And before someone says this is weight loss mediated, 1.) it's not. 2.) because weight loss was similar between the two drugs despite Reta being a shorter trial 3.) because glucagon is lipolytic & 4.) there's some deep mechanisms at play here. Enter ApoC3 and ANGPTL 3/8
Let's start with the plain lipids and I'm gonna directly compare with tirzepatide here to highlight immediately the differences big difference here. 48wk vs 72wk trial and yet a 41% reduction in trigs, 22% in LDL and 18% in total C. Reta is on a different level.
Full 80 week retatrutide obesity data will be revealed in 45 days!
I want to highlight a couple things besides weight loss from phase 2 that were shocking at the time and will be MORE shocking in phase 3 data.
For my cardiology & lipid nerds this thread is for you!
1/
*Rosuvastatin enters the discussion*
Love that some of my patients have LDL cholesterol levels in the high 20s/low 30s with no medications meanwhile I'm over here on lipid lowering therapy just to hit an LDL of 70.
Not at all jealous of their beneficial genetic mutation.
I was just complaining today about how one of our local hospitals loves to discharge patients on hydralazine. Can't stand it! So many better options!
Yeah it's definitely a "mistake" anything to slow down us providers with extra bureaucracy. Same with prior authorization
Meanwhile this is where some of the business AI is at currently:
Insurance letter: It appears your patient is noncompliant with their medication.
Also insurance letter: Shows that the patient has filled their meds on time for the last year.
Me: 🤔🤔
This feels very much like an AI generated slop letter given the absurdity of it.
🚨NC followers🚨
I heard that!
14 month old nowadays will just walk up to the fridge or pantry and point until we either get milk from the fridge or she'll pick a snack from the pantry. Girl knows what she wants 😂
That stretch of 75 southbound from the I-40 split to Cleveland TN is basically the Autobahn interrupted only by the occasional semi truck in the left lane.
Definitely has the Midwest likeability and proven track record as Transportation Secretary. Would be quite the flip from our current situation.
4 year old doesn't want to share with 14 month old. 14 month old is teething and cranky. I'm doing the single parent thing as wife is out of town this weekend. Robot vacuum sucked up a cat toy and sounded like a dying giraffe. I've already had 200mg of caffeine working on another 100mg now. 🥴
Shout out to Quemliclustat a CD73 inhibitor drug that's so unknown it doesn't even have a Wikipedia page yet.
But it turned 3-6 months to live to 15 months and counting so far.
Shout out to Quemliclustat a CD73 inhibitor drug that's so unknown it doesn't even have a Wikipedia page yet.
But it turned 3-6 months to live to 15 months and counting so far.
Oh man. I've got corn meal and flour and buttermilk....might have to make some hoe cakes tomorrow!
My FIL has pancreatic adenocarcinoma right now. He's on a new experimental chemo that has, for now, turned the cancer into a ball of necrotic tissue. Unfortunately that made the liver a wee bit angry. But still he persists. And still we hope and enjoy every day we can with him still here
Which 3?!
I *KNEW* this would happen sooner than later and of course Richard DiMarchi is involved.
Who needs GLP1 when you can just use GIP and Glucagon?
And guess what? It works in mice and monkeys essentially as well as Retatrutide with less side effects because there's no GLP1 agonism involved!
I mean Eli Lilly is running a trial of a selective Amylin agonist + GIP agonist for weight loss.
My best guess is that combo could easily lead to 20% weight loss with placebo-like side effects.
Ironic indeed, but science is always advancing.
