@nytimes.com another bad Alzheimer piece. Citing a study with negative primary endpoints as encouraging, mistaking prevention for treatment, puffing up an uncertain mechanism. How about lean into our ignorance until semaglutide reads out? www.nytimes.com/2025/01/31/w... - ThreadSky

dweisman.bsky.social • 21 days ago

@nytimes.com another bad Alzheimer piece. Citing a study with negative primary endpoints as encouraging, mistaking prevention for treatment, puffing up an uncertain mechanism. How about lean into our ignorance until semaglutide reads out?

https://www.nytimes.com/2025/01/31/well/mind/ozempic-alzheimers.html?unlocked_article_code=1.tk4.qTao.ruZAt_xZFVNy&smid=bs-share

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casepez.bsky.social•21 days ago

Unfortunately, lots of scicom folks echoed these assertions without doing their research and due diligence. @hankgreen.bsky.social was one of them. 😔

dweisman.bsky.social•21 days ago

Didn't catch that, but there is so much nonsense out there. Now that RK Jr leaches onto the false narrative, the Espay pre-print debacle happened, two approved drugs, I hope to see the pendulum swing back into rationality.

casepez.bsky.social•21 days ago

If it doesn’t sway naturally, we’ll have to shove it with evidence. 🖊️ 🗡️

nvillain-alz.bsky.social•21 days ago

Agreed! No mention of the EVOKE/EVOKE+ ongoing trials, and misleading report of the Phase 2 ELAD trial: first and foremost a negative trial! Let’s stick to the evidence and apply the same rigor for every drug!

dweisman.bsky.social•19 days ago

I'm a bit skeptical about taking epidemiology into clinical trials with little MOA, because it makes what's already a long shot into a moon shot. I'm also wary of anything that sounds too good to be true, and this fits the bill. That said, we will see...

sfackley.bsky.social•19 days ago

Observational trials are coming out with hazard ratios of 0.3-0.5, but don't consider educational gradients in access or the possibility that incipient dementia could limit prescribing of injectable drugs.

There may be benefit, but I suspect nowhere near as large as is being reported.

sfackley.bsky.social•19 days ago

I also suspect the first diabetes drug you're treated with has apparent benefits (e.g., my and others' work on metformin). And some people are getting GLP-1s as first-line therapy now--e.g. if BMI>35 and non-diabetic.

sfackley.bsky.social•19 days ago

I think REWIND is our best evidence to date, because people were randomized. And it paints a far less optimistic picture with HRs around 0.9.

https://www.sciencedirect.com/science/article/pii/S1474442220301733?via%3Dihub

sfackley.bsky.social•19 days ago

Of course GLP-1 enthusiasts will say that these aren't the newest drugs most effective for weight loss. But the older drugs do still cause weight loss...

Looking forward to the EVOKE trial results.

dweisman.bsky.social•19 days ago

Interesting. Weight loss is common prior to the diagnosis of Alzheimer’s, which would also decrease the use of these drugs.

Bottom line is that we don’t know until we have real data.

sfackley.bsky.social•19 days ago

I'm not sure if the weight loss in preclinical AD is large enough... but it could be if someone is going in a "good" direction or even stable wrt weight, blood pressure, glucose, HbA1c etc., they wouldn't get put on a drug.

dweisman.bsky.social•19 days ago

Exactly. "Looks great, no need for these injectable meds, you're doing fine."

nvillain-alz.bsky.social•19 days ago

And which could also be responsible for functional unblinding during the trial (so sad Madhav has disappeared from social networks, he’d have loved my comment ;)

dweisman.bsky.social•19 days ago

The price of having a deep expense account. Everything is a trade off.

nvillain-alz.bsky.social•18 days ago

These results on PD just confirmed your concerns...

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02808-3/fulltext

dweisman.bsky.social•18 days ago

Smart quote at the end of this (very good) NYTimes piece: “I wouldn’t do another study like this unless you learn what is the target,” Dr. Standaert said. “What is the biochemistry you are trying to change in the brain? How do these drugs work, anyway?”

https://www.nytimes.com/2025/02/04/health/parkinsons-disease-exenatide-byetta.html

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