63 Comments
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Chuck Craton, M.D.'s avatar

Every internist can tell you stories of patients they lost to cirrhosis or HCC from MASLD/MASH. Taking care of a 55 year old now that desperately needs a liver transplant, but other factors mean maybe one or 2 centers in the country could do it even potentially. Heartbreaking (and I see his parents as well and see their pain). Any tool I have to help prevent this is a tool I want. Yes diet (esp. Mediterranean) would help but most people just don't stick with it.

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Larry J Miller MD's avatar

I have used Semaglutide on hundreds of patients with remarkable success. My approach is to use GLP-1 to kick start the weight loss program. Mine called Thin4fun, uses 12 steps for permanent weight loss in a fun way. One of my patients, BD, began on semaglutide for 3 months and then converted over to my program. He has now lost 205 pounds and has kept it off for 2 years. Unless patients are willing to change their diet, drinks and lifestyle, I will not prescribe GLP-1.

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Michael Plunkett's avatar

Fat people get fat livers. No fatties, no fatty liver disease (by whichever euphemism you choose). 50 years ago the average American male weighed 70 kg. The female 50 kg. In Austria they still weight that and they don't have fatty liver disease. And GLP1s are for life.

They are a good idea. Only thing that has worked so far. Pretty safe. But ...

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Ryan Cooley's avatar

That is not what you stated. Both seed oils and UPF’s result in more calories consumed, anywhere from 500-1000 calories per day, wrecking energy balance

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Steve Cheung's avatar

This is a far better trial with far more meaningful endpoints than some of the Semaglutide stuff in the cardiovascular space of late. Glad to see it’s not all glorified marketing masquerading as science.

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Marianne Montemurro's avatar

Is the benefit to the liver from the weight loss alone or is there another mechanism of action involving the drug? If someone were to lose significant weight via a different method would the benefit to the liver be the same?

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Quark's avatar

I would love to see a trial where placebo is a LCHF/Ketogenic diet - Anything a GLP hormone can do, real food can do too.

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Benjamin Hourani's avatar

Presently, the GOP‘s seem like God‘s gift to medicine. Regarding MASH there is clearly a benefit as well as a seemingly endless series of diseases. It seems like the US always treats with medications rather than lifestyle.

The Europeans are not fat because they walk. They don’t ride in cars and sit in the drive-through lane at McDonald’s contaminating the environment with carbon emissions while waiting for their. Big Mac,fries, and milkshake.

European generally buy their food fresh and eat healthy, but most importantly they exercise infinitely more than the “big fat American“. Yes mash is a bad disease, but why must we always throw expensive medication’s to prevent people from developing a healthy lifestyle. The easy way out, long-term, is not always the best way out.

The problem with getting a control group for weight loss/exercise alone is difficult to impossible in this country because people are lazy and eat fat in spades.

Ben Hourani, MD, MBA

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Jacob Gardner's avatar

Thank you for this article! If all we ever talk about is failures and what is going wrong in the world…we may forget or fail to recognize what is going right…which means we may stop doing the things that are working.

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Daniel Low's avatar

Yup. Let’s put people on another drug for the rest of their lives. Sounds like a great investment, until something turns up that we didn’t count on, hmmm.

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Premedica's avatar

Hi! Nicely written article. I hear of mostly positive results in clinical trials for these drugs. I wrote my first article on a contrasting stance to GLP drugs/ozempic, and potential psychiatric excacerbations. Please take a look if you are interested :) https://open.substack.com/pub/premedica/p/the-dark-side-of-diet-drugs-what?r=59bm4t&utm_campaign=post&utm_medium=web&showWelcomeOnShare=false

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Critical Thinker's avatar

Mmmm… Did the “drug” shred the bad effect of fatty inflammation in liver or, did “weight loss” do it?

Instead of promoting more pharmaceutical products, I would discuss how astoundingly criminal it is that our health care policymakers do nothing to control the obesity epidemic in the US, despite its devastating effects on our health.

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Evelyn Duvivier's avatar

Dr. Mandrola, Considering wgt loss is almost certainly the key to the trial's success (which I admittedly have not read) and that stopping Semaglutide leads to rapid wgt gain in many people, are you proposing people stay on Semaglutide for life?

Can you please address this question in the open session for subscribers?

(As well as here)

Dr. Cifu shares your enthusiasm for Semaglutide. But should the Rx not be a bridge to better health, then stopped? It's the stopping that's the problem.

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jack jacobson's avatar

How would this compare to treatment with a ketotic diet? Why do we try to treat everything with a drug, when there are alternatives that don't require them?

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Randy's avatar

There is a natural treatment for NAFLD that has shown promise in animal research studies — Akkermansia muciniphila. (Available from Amazon. Search: B0DK9HHSCX)

“A. muciniphila and their extracellular vesicles alleviated non-alcoholic fatty liver disease (NAFLD) by inhibiting inflammation in a high-fat diet/carbon tetrachloride-induced liver injury model in mice.”

— Source: https://drive.google.com/file/d/1Rd5ioo9trsCvnVcxMYJhC3uwulnOV31I/view?ts=68160cd5&pli=1 (p.11)

“In conclusion, the present results showed that oral administration of A. muciniphila and its derivatives for four weeks could enhance anti-inflammatory responses of the colon, adipose, and liver tissues and subsequently prevent liver injury in HFD/CCL4 mice.”

— Source: https://www.nature.com/articles/s41598-022-06414-1

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RAO's avatar

Is this for the general population as a preventative, or only for those who are overweight or who have liver disease?

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Randy's avatar

I really can’t expand on the conclusions of the researchers quoted above. Remember that these are animal studies, which usually precede human studies by more than a year. But frankly, there will probably never be human trials of A. muciniphila, because as a natural substance, there’s no big bucks in it. A 30-day supply of the supplement is $20-ish on Amazon vs $700 to $1400 per month for GLP-1 injections.

The best answer I can give is that after studying the research, I ordered a 30-day supply for my overweight wife and overweight self. We’re not mice, and neither of us have liver disease, but other studies (included in my first citation above) report that “it is noteworthy that clinical trials have confirmed that a 3-month intervention with a pasteurized form of A. muciniphila supplementation [identical to the Amazon product linked] resulted in a significant increase in insulin sensitivity index of about 30%, as well as improvements in body weight, cholesterol and triglyceride levels” (p.15). Hope this helps, RAO.

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RAO's avatar

Fascinating. I'd still want to take something like this under a doctor's care. I'm not overweight, but two of my children have T1 diabetes. My mom had T2 diabetes (among many diseases, including heart stuff, stroke), so I suspect I'll have to deal with it at some point. Just looking into things that might help me, given the hereditary factors in my family.

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Crixcyon's avatar

Only the lost depend on drugs to fix problems. Drugs for life is the blanket mission statement for big pharma's medical mafia. Absolutely no consideration as to what causes these problems to begin with and how that behavior can be managed and turned around. Drugs will NEVER reverse the root causes of your ills.

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Aaron Clancy's avatar

Presuming that this trial ends favorably, how long does it generally take for the FDA to approve a drug for another indication ( ie NAFLD)?

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