David W (aka Flex NP)

17h

Mark my words. When the Surmount MMO trial shows that 5 years of tirzepatide will reduce your risk of obesity related cancer, I'm going to point back to this post. That's quite the correlation(especially for men)

Eric Topol@erictopol.bsky.social

The link between obesity and early-onset cancer. A nationwide study of 6.3 million people, age 20-39, with no prior cancer, by BMI and waist circumference, with 11 year follow-up, in South Korea acpjournals.org/doi/full/10....

David W (aka Flex NP) reposted

the-incretins.beehiiv.comReversing 50 years of glucagon dogma in one summerRewriting the textbook on glucagon and insulin sensitivity

Our framing of what glucagon does, and does not do in the body has massively shifted in one summer. No longer should we just view it in a narrow lens of increasing blood glucose. But rather for its profound metabolic benefits. Starting with improving insulin sensitivity and improving liver health.

the-incretins.beehiiv.comReversing 50 years of glucagon dogma in one summerRewriting the textbook on glucagon and insulin sensitivity

This has gone on behind the scenes for years in preclinical trials but now with survodutide and retatrutide we have two different drugs that have thrust these benefits center stage in humans. Time to update your priors and not fear glucagon. It's here to help.

Garden post: it's October 25th. It has not frosted at my house in Michigan. My peppers especially my poblano peppers are going crazy still producing. And no frost in sight for the next 10 days. Super El nino + climate change doing a thing. Never thought I'd have pepper plants alive in November!

Re-upping this for the Sunday morning crowd. New Incretin Space article tomorrow about how glucagon agonism profoundly improved insulin sensitivity and helps with GLP1 to drive glucose down, instead of up, like so many of us were taught.

David W (aka Flex NP)@rnflex.bsky.social

This week Eli Lilly presented data for a trial I've been waiting to see SOME results for a year now! Retatrutide and chronic kidney disease. It was a short trial. As we'll find out, TOO SHORT! And these are literally just the topline results to see if Reta changed measured GFR #NephJC

Final thoughts. This trial is compelling leaves me with MORE questions. I need to see the laundry list of other labs they captured(24 hr urine albumin, electrolytes, multiple markers of kidney inflammation, glucagon, cAMP, vasopressin, metabolomics etc etc.)

I still think this GFR rise is real, but needs a longer period of time to show up. I'd love to see the subgroup breakdown (diabetic vs non-diabetic) to see if there's any differences. I know a handful of reta trial patients who HAD CKD & now have sustained & normal GFR leaves me with many questions!

Next, we have RARI, a measure of renal artery resistance, and RVR and change in intraglomerular pressure, 2 of out 3 of these are significant. RARI is similar to sema studies. Change in glomerular pressure is new. That's not been seen before in GLP1 meds. Glucagon alters TGF! Longer study!

Finally weight loss was about 13%. Change in BP was huge, -14mmHg adding another confounder to these findings. That's a huge drop in BP that could be altering some of these renal metrics. Again a longer trial would help! These patient had only been on 12mg for 8 weeks!

In the subgroup that had microalbuminuria (avg 131mg/g) Reta reduced UACR by 50%(!!) versus placebo. Small n, but really nice to see. There's a diabetic trial of reta in patients with severe CKD that wraps soon, so we'll see how durable this effect is in a 350 patient, 52 week trial.

In terms of renal blood flow, there was no statistically significant difference in either, though there was a slight numerical difference. Again a longer, bigger trial would have helped here.

Zoomed in, Cys-C crashes back to baseline after 4 weeks. Creatinine does not(cuz of weight loss) but this suggests some sort of drug mediated effect that we might be missing. Glucagon has direct effects in the kidney. I'm shaking my fist at Eli Lilly for not running this trial longer! Ugh moving on

Reta was associated with a fairly rapid decline in fat around the kidney and a small but statistically significant decrease in sinus fat within the kidney. All good things for reducing the effects of inflammatory of adipose tissue

Here's the patient characteristics, RAAS use was high ~94%, SGLT2i use was low, 21% to avoid confounding. It included diabetics and non-diabetics. They did not split out mGFR difference between diabetic vs not diabetic. I hope we see that at a later date, mostly CKD3a patients

Primary result was...null. No change in mGFR at 24 weeks however, it was deflecting back upwards, and Cystatin-C and Creatinine were both rising. The trial needed to be longer! I think 52 weeks would really show whether this rise is real or not. In that same token look at Cystatin-C follow up

washingtonpost.comBreakthrough vaccine for the deadliest skin cancer cut risk by almost halfThe skin cancer vaccine is based on mRNA technology that helped end the coronavirus pandemic.

Age of wonders that melanoma, 20 years ago was a literal death sentence, and rest assured it's still a deadly cancer. But now, you've got more than a fighting chance against it.

Ana Marie Cox@anamariecox.com

Enormous news. A melanoma vaccine, one of the most deadly cancers out there. Science is good and helpful and there should be more of it. www.washingtonpost.com/health/2026/...

Flu and COVID vaccines are done for the whole family including the 20 month old and 5 year old. Ready as we can be for the winter respiratory season!

Retatrutide for sleep apnea published today. Very severe sleep apnea, AHI near 60! I had OpenEvidence compare to Surmount OSA. Despite being a sicker and heavier cohort Reta still had similar benefits in reduction of sleep apnea as Tirz. @proptermalone.bsky.social

NEJM.org@nejm.org

TRIUMPH-1-OSA and TRIUMPH-2-OSA: In two phase 3 trials involving participants with OSA and obesity or overweight with or without type 2 diabetes, treatment with retatrutide was found to result in greater decreases in the apnea–hypopnea index than placebo. https://nej.md/4BmAHOI #SleepEurope2026

About half of patients without diabetes shifted to no sleep apnea or mild OSA. Hypoxic burden was reduced by about 70% From a cardiometabolic improvement standpoint Reta remains undefeated here as well -13mmHg drop in BP, hsCRP ⬇️ 60% LDL cholesterol ⬇️ ~24%(lol what?!) and triglycerides ⬇️ ~40%

David W (aka Flex NP) reposted

Eli Lilly continues to push aggressively start new trials. Now we have coformulated Eloralintide and Tirzepatide "EloraTZP" phase 2 trials showed it caused retatrutide like weight loss in less than a year. It caused the largest drop in A1c in diabetes in any clinical trial in HISTORY.

clinicaltrials.govClinicalTrials.gov

clinicaltrials.gov/study/NCT078... clinicaltrials.gov/study/NCT078... Couple other notes. Both trials are measuring change in GFR. Eloralintide alone seems to raise GFR by about 4-5ml/min For DM2 a composite endpoint of >15% WL AND A1c <6.5% is wild to see.

Here I was excited for Retatrutide's FDA approval next year, and I still am! But somehow, the same company has created an even MORE potent drug than retatrutide. Not sure we've ever seen anything like this in drug development...ever?

Enter the Amplify 1 & 2 trials. Amplify 1 is in obese non-diabetics and must have a BMI >35 due to the expected bariatric surgery weight loss. The trial lasts 2 YEARS. Trial length is a surrogate for weight loss. We should expect 35% ON AVERAGE with a trial this long in non-diabetics. Not kidding.

For diabetes, expect 25% at the low end with higher doses probably hitting 30% in diabetics! I'm expecting A1c reductions that could hit 3% between the weight loss and reversion to normoglycemia that might approach 80% or higher. This is unprecedented in medical history.

Most SVTs don't require much treatment but time & NSAIDS, but the wild card here is if it was big(>5cm or longer), within 3cm of a deep vein, or involves the greater saphenous vein then it's time to spin up blood thinners. Will be curious to see what the actual truth & diagnosis is here.

ghost malone ergo propter bones@proptermalone.bsky.social

right, and (again my naive understanding) is that if it was just superficial blood clot that would be the right approach. but failing to dx the deep clots is a pretty big miss

Big couple weeks for retatrutide and tirzepatide coming up. We get Reta + Tirz data on Thursday for CKD. The sleep apnea data for Reta is on Friday. And then in early November we get the Reta + knee arthritis data! Then mid November cardiometabolic risk data for Reta, data overload!

Nerd post: There's a certain level of satisfaction while researching my next blog post about glucagon agonism reducing hepatic insulin resistance & noting to myself 'seems to be an asymptotic limit' and finding a research paper that says reducing hepatic IR has "asymptotic physiological limit" 😍🤓

Roasting the last 5 pounds of my backyard garden poblanos over an open oak fire to be chopped up and frozen for salsa and tacos con poblano come winter.

Every time I'm like huh, weird that Lilly is studying *insert disease* with GLP1 meds, then some observational data comes along and shows exactly why they're dropping millions to study these seemingly disparate indications that have nothing to do with weight or diabetes @beckya.bsky.social

The Lancet@thelancet.com

GLP-1s associated with reduced need for acute psychiatric care for people with schizophrenia and type 2 diabetes, study of US data suggests. Find out more in @thelancetpsych.bsky.social: spkl.io/633257X6fJ

thelancet.comGLP-1 receptor agonist initiation and risk of psychiatric hospitalisation and emergency department presentation in adults with schizophrenia and type 2 diabetes in the USA: an observational cohort stu...GLP-1-based therapy initiation was associated with lower psychiatric acute-care use than non-initiation and initiation of DPP-4 or SGLT2 inhibitors in adults with schizophrenia and type 2 diabetes. Po...

In another instance of what can't GLP1 meds do? Reduce schizophrenia hospitalization risk? Caveats: Observational data only! Chaser? Eli Lilly has a RCT studying a GIP/GLP1 dual agonist in schizophrenia right now. So we'll find out soon if this is real.

Double chaser? Most atypical antipsychotics used for schizophrenia cause weight gain, insulin resistance, worsening lipid profiles. A dual agonist drug would directly counter that improving their health as well. Link to the Lilly trial: trials.lilly.com/en-US/trial/...

akdh.orgIntegrating Pediatric and Adult Hypertension: Advances in Mechanisms, Therapeutics, and Clinical CareHypertension is increasingly recognized as a life course public health issue, with origins in childhood and consequences that extend into adulthood. Recent evidence demonstrates that the incidence of ...

Progress in cancer treatments continues to be remarkable.

NEJM.org@nejm.org

In a trial involving adults with Ph-positive acute lymphoblastic leukemia, 24-month event-free survival was 86% with the TKI–immunotherapy combination ponatinib–blinatumomab and 67% with imatinib plus chemotherapy. Full phase 3 GIMEMA ALL2820 trial results: https://nej.md/4scorw0

David W (aka Flex NP) reposted

Nephrology Journal Club

@nephjc.bsky.social

1/10 #NephJC #TenPostNephJC. #NephTwitter Patient outcomes are better with transplant vs dialysis. Is this always true? What about high-risk donors (expanded criteria donor-ECD) or recipients (elderly with DM or CVD)? Read the article 👇 link to article on pubmed.ncbi.nlm.nih.gov/42759976/

David W (aka Flex NP) reposted

Swapnil Hiremath 🍁🇨🇦

@hswapnil.medsky.social

Replying to @hswapnil.medsky.social

And here’s our editorial - www.akdh.org/article/S294... There should be a second issue coming out soon!

Am I working primary care today or ER. Jeebus that was an intense morning of rather concerning pathologies back to back to back to back to black

I see denying appropriate medical care continues to remain profitable 😐😐😐

George Pearkes@peark.es

$UNH absolutely smashed estimates this AM, medical loss ratio 1.5%-pt lower than estimated as revenues beat by 2% and adjusted EPS beat by 14%. FY guidance raised from $19.50-$20.00 to "at least $20.50".

David W (aka Flex NP) reposted

the-incretins.beehiiv.comSurv-ing up DiabetesSurvodutide syncs a type 2 diabetes win with caveats

The parade of new diabetes results continues on. This time it's Survodutide in diabetes. At first blush, the results seem modest but a closer examination reveals some very compelling metabolic benefits, plus another call to end placebo controlled trials for GLP1 meds. Read and share!

Good news of the day? So many people at my clinic want a COVID vaccine that we actually ran out today!

the-incretins.beehiiv.comSurv-ing up DiabetesSurvodutide syncs a type 2 diabetes win with caveats

academic.oup.comThe imperative for improved antihypertensivesAbstract. Hypertension remains a leading modifiable risk factor for cardiovascular morbidity and mortality worldwide, yet blood pressure (BP) control rates

404 Not Found: GLP1 meds not mentioned as adjunctive hypertensive meds. Cuz they are. Especially if your BP is uncontrolled to start.

American Journal of Hypertension@amjhypertension.bsky.social

From our special issue: The imperative for improved antihypertensives #OpenAccess

19 month old took a bite of these dumplings(recipe is wife's family Hungarian butter dumplings) Anyways. 19 month old looked like she saw God after that first bite. Devoured 3 more in rapid succession. Wish I'd have videoed it 😅

David W (aka Flex NP)@rnflex.bsky.social

60 and rainy calls for homemade chicken and dumpling soup from scratch.

60 and rainy calls for homemade chicken and dumpling soup from scratch.

Many of the OG antidepressants and anti psychotics came about from research into allergy medicine, specifically anti histamines. Also those original antipsychotics can also prevent nausea and vomiting. The human body is weird. Pushing random buttons indeed especially back in the 1940s/50s

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The opposite is true for some drug research. GLP1 was a tantalizing target for like 2 decades before we figured out a med for it. KRAS mutations in cancer are another. Sometimes we know a target but drugging it is extremely difficult!

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Apparently this is your 40s. Buy fancy French door air fryer/rotisserie/toaster/do it all small appliance. Or maybe it's the 2 small children who demand hot food quickly and this is faster than a full size oven 🙈🤷