FlexNP

Primary care NP, lover of balanced glucagon agonism, incretin nerd, photographer, mountain lover, coonhound rescuer

[FlexNP @rn_flex]

@EricTopol Good thing Surmount MMO with tirzepatide has new cancer diagnosis as an exploratory endpoint then, because that HR for this observational trial is certainly compelling.

[FlexNP @rn_flex]

@DrNadolsky Glucagon shill actually 🤣

[FlexNP @rn_flex]

So anyways GLP1/GIP/Glucagon agonists are fasting mimicks as glucagon induced ketosis and GIP and glucagon agonism both drive down insulin secretion.

Just saying.

[Dr Amol Akhade @SuyogCancer]

Short-term fasting during neoadjuvant chemotherapy for advanced ovarian cancer is one of the more intriguing non-drug interventions presented at #ASCO2026.

The study met its primary endpoint: fasting prevented the chemotherapy-associated rise in insulin levels and demonstrated a favorable metabolic shift.

The headline result was a PFS signal:
• mPFS 38 months with fasting vs 24 months with free diet •
HR 0.26 • Log-rank p=0.045

Before we get too excited, several important limitations deserve attention:

🔹 Only ~18 patients per arm after exclusions
🔹 Trial was powered for insulin changes, not PFS
🔹 Open-label design
🔹 Borderline statistics (95% CI 0.06–1.00; Cox p=0.056)
🔹 Multiple secondary and exploratory analyses increase the risk of false-positive findings
🔹 BRCA-mutated patients were more common in the fasting arm (50% vs 33%), which could influence outcomes
🔹 Median follow-up was only 16 months despite reporting a large difference in mPFS
🔹 Immune findings were hypothesis-generating with p-values around 0.06–0.07
🔹 Analysis appears vulnerable to selection bias from withdrawals and compliance-related exclusions

The most convincing finding is that short-term fasting is feasible and biologically active, affecting insulin and metabolic pathways.

The least convincing finding is a 14-month absolute PFS improvement from a dietary intervention in a 36-patient study.
Interesting study.
But extraordinary efficacy claims require validation in a larger multicenter randomized trial before fasting enters routine ovarian cancer practice.
@OncoAlert
@ASCO #asco26

[FlexNP @rn_flex]

Just pointing out the similar outcomes in terms of immunosuppressant effects...

[FlexNP @rn_flex]

@JCanNuSH Bunch of those phase 1 cancer and lipid drugs have reported out recently. But yeah. I troll clinical trials .gov for their stuff and it's getting harder to find

[FlexNP @rn_flex]

@bioinvestor24 Will see more vesper data in a few days but wondering if they're going big on the combo because MET097 alone is just middle of the road weight loss?

[FlexNP @rn_flex]

@ManOnThePen @StadlerScott @DanielJDrucker @JCanNuSH @bioinvestor24 @ResearchPulse1 @BevTchangMD Appreciate it. I'll be at ADA this week and will have a ton of writeups coming from all the data we'll be getting!

[FlexNP @rn_flex]

@bioinvestor24 And now Lilly with this for a rare subset of lung cancer. Just wild survival curves.

https://t.co/sipB6yLOQK

[Eric K. Singhi, MD @lungoncdoc]

Ladies and gentlemen, we officially have a NEW standard of care in resectable RET fusion+ NSCLC.

LIBRETTO-432: Adjuvant selpercatinib x 3 yrs vs placebo:
🔹Stage II–IIIA 2-yr EFS: 92% vs 61%
🔹HR 0.17, P<0.001

Overall stage IB–IIIA:
🔹2-yr EFS: 94% vs 70%
🔹HR 0.16

#ASCO26

[FlexNP @rn_flex]

@ManOnThePen @bioinvestor24 Given how far ahead they are on just molecules and aggressively targeting new indications, I'm not sure they're necessarily worried.

They're presenting on Tirz, Reta, Elora, Orfo, & Mazdutide just at ADA...kinda nuts the amount of data they have

[FlexNP @rn_flex]

@alnafisah1994 @DrNadolsky @JCanNuSH @Doctor_Salomon Not necessarily just that. But also sharp peaks and troughs can elicit side effects too, along with the shape of the molecule etc. Multiple factors it seems

[FlexNP @rn_flex]

@ManOnThePen All very true. And keep an eye at ADA there's formulations in development for both oral formulations of Lilly drugs and once monthly injectable formulations. The market is dynamic and continues to innovate.

[FlexNP @rn_flex]

@DrNadolsky @JCanNuSH @Doctor_Salomon I'll just say without breaking embargo rules, the fasting insulin, insulin sensitivity & HOMA-B data on orforglipron is very compelling knowing it has zero B2 arrestin activity(and also it might make a difference that it's a small molecule and not a peptide)

[FlexNP @rn_flex]

@DrNadolsky @JCanNuSH @Doctor_Salomon Lilly has made it a point to build biased agonists in general(Tirz, orforglipron) minor exception is Reta. Which is still biased towards cAMP but does have a little bit of B2 arrestin activity but still significantly less than semaglutide. It's a bit Greek Jen don't feel bad 😂

[FlexNP @rn_flex]

@CristinaDeReins One trial I'll be keeping a close eye on is ATTAIN-HTN. It's testing oral non-peptide GLP1 med orforglipron for HTN. In pre-existing HTN patients it ⏬ SBP ~15mmHg even with low doses (in first 8 weeks) Could be an unconventional but beneficial adjunctive therapy in the future!

[FlexNP @rn_flex]

@DrNadolsky Brute force approach 😂

[FlexNP @rn_flex]

@bioinvestor24 Also timing wise. They were testing dual agonist GIP/GLP1 at same time as Sema and over 12 weeks saw similar results but the dual agonist was a daily dose so they went forward with Sema instead because of weekly dosing...fateful decision there.

[FlexNP @rn_flex]

@DrNadolsky @Ashwinreads Broadly agree.

Also think market isn't huge, but the so called "skinny fat" and older patients with low muscle mass could benefit massively if integrated with monitored resistance training

[FlexNP @rn_flex]

@bioinvestor24 I think the broader point is by the time anyone else has a competitor to Tirz/Reta they'll have gone full keytruda on FDA indications. Asthma, hypertension, Crohn's and UC, IBS, psoriasis, back pain, arthritis, substance use disorder, multiple mental disorders on and on...

[FlexNP @rn_flex]

@bioinvestor24 Yeah all preclinical, there's 3 being shown on posters at ADA. ASC39, VRB103 and ACCG2671