Michael Mindrum, MD

@cremieuxrecueil 😂

Has anyone else noticed that Eli Lilly's pipeline seems suspiciously focused on making it possible to have a really good weekend in Vegas?

@NeilFlochMD Yes

As I have been saying the future or present of obesity care is combination therapy.

@EricTopol @scisignal interesting study... a nightmare of an infographic.

By connecting the brain and pancreas, activation of the vagus nerve increases insulin release after eating. But with obesity the opposite occurs! Now we know why (NO-nitric oxide, Nos-nitric oxide synthase, KO-knockout). From experimental model work @scisignal science.org/doi/10.1126/sc…

Interesting study and absolutely horrible infographic.

1/5 I'm a cardiologist. I have spent twenty years watching cholesterol destroy arteries, trigger heart attacks, and kill people I care about. Today, Eli Lilly presented data that may begin to end that era. VERVE-102. A single infusion. One dose. It uses base editing to permanently turn off the PCSK9 gene in your liver. Presented today at the European Atherosclerosis Society Congress: 88% reduction in PCSK9. 62% reduction in LDL cholesterol. Sustained up to 18 months. No treatment-related serious adverse events. One infusion. Not daily pills you forget to take. Not monthly injections. One dose — and your cholesterol may stay low for the rest of your life.

@MartinShkreli @0xMasonH Why do you say not that valuable?

@0xMasonH eh this is not that valuable, no one wanted it, lilly didnt pay much for it

It's a shame that this is likely 6-8 years from hitting the market

Color me surprised!

The curse of delusions and mass hysteria strikes again.

We will obliterate heart disease in my lifetime. 🍿

@MohammedAlo A bullish take on pharmacotherapy!

@MichaelMindrum When you come by GLP1s with several of the older medications you end up with incredible amounts of weight loss beating bariatric surgery and keeping the weight off forever.

We still have a long way to go to treat and manage obesity effectively. We need more access to surgery and to medical therapy. Medical therapy has downsides: many people don't have access, and many others discontinue treatment within a year. There are side effects to contend with, a lack of proper medical supervision for many, a lack of education and unreasonable expectations, cost, lapses in insurance, and intentional barriers set up by insurers. Even when the response is excellent, a significant portion of patients would benefit from further reduction in adiposity to improve their obesity-associated complications. These patients would benefit greatly from bariatric surgery, with or without drug therapy. Writing a prescription is easy. Creating a pop up telehealth pill-mill company selling drug to vulnerable population without proper medical supervision is profitable. Discussing obesity as a complex chronic disease, sharing with a patient the brain biology of obesity, explaining how different interventions fit into long-term weight management, setting reasonable expectations, and matching the intervention to the disease takes expertise, time, and patience. For some behaviour change is perfect, others will benefit from drug therpy, others bariatric surgery, and others will benefit from all of the above. It needs to be a rational and well - understood process. The medical system needs to be arranged in a way that reduces the friction between a patient's disease state and effective treatment pathways: longitudinal programs informed by behaviour change psychology, proper medication supervision, cohesive and seamless referral pathways to bariatric surgery, and access to surgeons who have adequate time and support to perform surgeries at increased scale. We still have a long way to go.

It feels very futuristic to imagine a world with one-and-done therapies that lower LDL cholesterol for life, but... it might not be far off! These are new phase 1 data for Verve/Lilly's PCSK9 base editor: one single intravenous infusion reduces LDL cholesterol by as much as 60%

Eli Lilly has done it. They've gone and made what seems to be a powerful, permanent gene therapy for LDL cholesterol. That means they'll be able to effectively prevent most heart disease with a single infusion!

The difference between people in long lived populations and those with chronic disease in western populations is not willpower. It’s the environment. If you take those same people from long live populations and expose them to the western environment many of them become obese. Does everyone have the same genetic vulnerability? No. Which is why some people can remain thin despite the environment.

@terrysimpson So glad we have many more tools that we had just 15 yrs ago but it can be a stubborn, frustrating, and at times devastating dz. I think we need to treat early and aggressively

@MichaelMindrum It is great when any can reverse disease for a bit - we saw this in patients with weight loss surgery -about 75% whose diabetes was found in the 2 years previous. Sadly with time some DM came back. Horrific disease

Some of my “Star” patients who placed their diabetes in remission with keto 5 to 8 yrs ago are coming back to see me due to diabetes rearing its ugly head again. These are among the most motivated of the motivated. The stubborn shadow of type 2 diabetes follows and it needs to be respected and not judged.

Anybody else notice that one Claude interface has very littel understanding what other Claude interfaces can do (i.e. Code, Co-work, and Web). It can be a bit confusing.

@BWVanderWelMD It is!

@MichaelMindrum Metabolic surgery is a great tool

@alt_w_v_g Could you analyze the ROI of marital counseling in your situation?

My wife mentioned a nice private school over dinner this week She said the campus was beautiful I asked what's the tuition She said we should look at it as an investment in him not a cost I made a note She said don't make a note I said I always make notes She said this isn't a deal I said everything is a deal She closed her eyes She said we'd discuss it Saturday I agreed Saturday 7:02am She came downstairs in her Saturday robe Coffee in hand I had my cargo shorts on The dining room had been cleared The projector was on The analyst was at the head of the table Quarter zip on, three iced coffees, a legal pad, and two laptops He had been there since 6:44am I texted him at 11:14pm Friday The text said dining room 6:45am bring the model He sent a thumbs up My wife stopped in the doorway She said what is this I said you said you wanted to discuss it She said this is not a discussion I did not respond She sat down anyway The analyst stood He said good morning ma'am She did not respond He sat back down A printed deck in front of each seat A fourth copy in case Slide 1 Tuition Schedule $38,500 per year Thirteen years $500,500 nominal Before escalators The school has raised tuition 4.2% per year for a decade With escalators $648,000 My wife said okay I said I'm not done Slide 2 Opportunity Cost Even before escalators $38,500 invested annually 10% nominal return S&P long-run average since 1928 By his eighteenth birthday $944,000 My wife said we can afford it I said I know that's not the slide Slide 3 Terminal Value at Age 65 $83 million She was quiet The analyst slid the sensitivity tables across the table 8% return $31 million 10% return $83 million 12% return $222 million She did not look She said this isn't about money I said it's always about money She said no it isn't I said then what is it about She did not answer She said you can't put a dollar value on his teachers his classmates his environment I said I can the analyst already did slide 6 He flipped to slide 6 She did not look She said the school is the best in the city I said best is a feeling She said it produces the best students I said the students were already the best before they got there She said our son deserves it I said our son deserves $83 million My son walked in He is five Dinosaur pajamas He looked at the projector He looked at the open deck on the table He looked at slide 3 He said are we modeling pre-tax or after-tax The analyst opened a new tab My wife looked at the ceiling He said what's the discount rate The analyst set down his pen She closed her eyes He said is this the same return assumption from the 529 conversation The analyst stopped typing He looked at me I did not say anything She stood up Sat back down He said dad can I help I said yes He pulled up a chair The analyst handed him a printout He started reading My wife watched him read She watched him for a long time She said his name He looked up She said do you like school He said the work is too easy and the kids don't ask questions She did not respond She looked at the ceiling She walked out of the room The analyst started packing up He said should I follow up Monday sir I said no follow up needed He'll be fine Sent from my iPhone

Ozempic is about to go generic for billions of people, including in India and China. The weight loss #obesity drug sold as Ozempic and Wegovy will soon go generic in countries that are home to 40% of the world’s population, significantly lowering the #price of a costly medicine. nytimes.com/2026/03/19/hea…

1/ Some things I've learned recently running coding agents on large-scale projects. Most of this contradicts advice from 6 months ago!