PART ONE: For this reader, the GLP-1 tirzepatide (sold as Zepbound) was a miracle

We live in a time of marginally useful, hugely costly drugs. For some people, GLPs may be a return to an earlier era - of insulin, penicillin, even ether - drugs that changed medicine and saved lives.

(First of two parts)

A lot of you have spoken out on the GLP-1 weight-loss/diabetes drugs since I asked about them on Tuesday.

First, almost 3,000 UT readers answered the poll. Of the almost 1,000 who had actually taken GLPs, two-thirds had a good experience. Only 1 in 8 said they had not worked.

Your comments and emails are even more striking.

People who have not taken the drugs express wariness of their side effects and long-term risks. They also pass on secondhand tales of woe.

But many people who have used them report good news. Not totally good. The GLPs cause constipation and other digestive problems, as well as more serious side effects.

Even so, they work. Putting aside the (mostly favorable) personality changes the Substacker Eugyppius reported, they cause significant, lasting weight loss in many patients. These are not celebrities using GLPs to lose a few pounds, but obese or morbidly obese people shedding enough weight to change their lives.

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(Know what else can be life-changing? The truth! Get your dose for pennies a day.)

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Is this effectiveness a surprise? Yes and no.

The clinical trials from Eli Lilly and Novo Nordisk, the companies that sell these drugs in prescription form, clearly showed they cause significant weight loss.

Yet we all have good reasons to be wary of clinical trial data. Clinical trials are the gold standard of medical research. Even so their results frequently translate poorly into the real world, especially for medicines designed for long-term use. The short-term improvement they capture often makes little difference clinically, especially for diseases that wax and wane on their own.

But for many Americans, obesity and the metabolic changes associated with it only worsen over time. The fact these drugs can reverse that trend for many is stunning.

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We have grown used — too used — to drugs that do not really work, drugs that are barely better than placebo or far cheaper, older generics, drugs that are heavily advertised but do not justify their hype. More recently, drug companies have focused on complex and expensive large-molecule biological medicines as maintenance treatments for diseases like rheumatoid arthritis. Even when they work, those biologics may affect the immune system long-term in ways we don’t really understand.

If the GLPs continue to demonstrate this level of efficacy with relatively modest side effects, even for a minority of patients, they will mark a return to an era that no longer seemed to exist in medicine, when relatively simple compounds offered life-changing benefits for millions of people — and for society as a whole — at low cost. The last drugs to have that kind of impact were HIV medicines.

(And, yes, the GLPs are effectively very cheap for the patients who get them on the grey market, a large group that happens to include both Eugyppius and the woman whose email follows. That issue is separate, and worthy of future attention.)

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So, without further throat-clearing, here’s the GLP email that hit the hardest of any that have arrived so far. I don’t think anyone reading it could doubt this woman wanted badly to lose weight and did everything reasonably possible to do so for years if not decades.

I present it unedited and cut only for length. These are her words, and her graph at the bottom. She asked for anonymity, which is fine by me, as she reveals detailed personal health information throughout.

It’s fairly long, even after the cuts, so I am going to offer a second part including with the questions I answered and her responses.

I hope you find it as striking as I did. It is easy now for me to see why so many physicians are optimistic about the GLPs. If even one-quarter patients have outcomes like this, these drugs will be the biggest advance in medicine in generations.

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Dear Mr. Berenson,

You wanted information in regards to GLP1s. I have a lot to say (sorry). I can’t afford to subscribe to your Substack at this time, but I wanted to have my say.

I found out I was insulin resistant 30 years ago (age 33) when I was dealing with infertility. At the time the only solution was to go on the diabetes drug, Metformin. I was on Metformin for the next 25 years. After 8 years of infertility treatment I had to give up the dream of a second child (baby number one was conceived easily).

I had many of the problems associated with insulin resistance: fatty liver (high liver enzymes), infertility, PCOS [Polycystic Ovary Syndrome], borderline high A1C [blood glucose], obesity, raging sweet/carb tooth, no real satiety instinct, etc. Metformin didn’t help any of those things but it was supposedly preventing me from becoming diabetic so I kept taking it.

My weight. I gained weight, overnight, in my mid-20s and weighed over 200 lbs from age 25. I”m 5’2”. I was obese when I got pregnant with my daughter at 30…

In 2013 on my 50th birthday at 245 lbs, I decided to give weight loss a big try. Over the course of 2 years I lost 75 lbs, my lowest since age 25, but no matter what I did I couldn’t lose more…

Still not giving up I worked out with a trainer. I saw a nutritionist. I did 5 months of the Atkins diet, provably in ketosis, Nothing. I could not lose another pound and if I gained a pound, I couldn’t lose it either. I did everything. My weight snuck up to 190 lbs. Then Covid hit and I gave up and I gained back to my starting weight, 245 lbs. I don’t know why I could lose 75 lbs but no more and could not lose any small gains.

Two years ago I decided to try tirzepatide (Note: sold by Eli Lilly as Zepbound) with the attitude that it probably wouldn’t work but I’d give it a try. I bought my medicine through a medispa, which I suspect got it on the gray market. It was a miracle from the first dose. I didn’t care about food including anything sweet. I got full easily and couldn’t eat more than half portions.

But mostly, I was steadily losing weight. It wasn’t falling off. I was losing 1-2 lbs a week, a healthy rate. After my years of weight struggles, I am an expert at counting calories, balancing protein, carbs and fats and working out. When I saw this thing just might work, it was easy to transition back to tracking my food and moving. For me, the satiety, elimination of “food noise” and loss of sweet/carb tooth are secondary. I’m primarily interested in the health benefits and weight loss.

Two years later, I have lost almost 100 lbs (1 1/2 lbs away!). My liver enzymes are well in the normal range (no fatty liver), my a1c is normal, I still get full really easily, and I’m still losing weight, just much slower, and am 16 lbs to goal…

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(Following the facts, wherever they lead, with your help!)

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Side effects: I had terrible indigestion at first. One morning I woke up thinking I was having a heart attack but an EKG proved it was very bad heartburn. Certain foods cause worse indigestion and I stay away from them. I have also had bouts of constipation but I manage it by prioritizing fiber. I’ve had two brief bouts of allodynia [Note: extreme sensitivity to touch], small, hand-size areas for less than a day each time. I’ve learned to manage the side effects and don’t have problems anymore.

After a few months of getting tirzepatide from the medispa, I learned how to order research peptides on the gray market. I’ve been getting my medicine that way since.

Today I would have another child if I had had access to tirzepatide 30 years ago. It is truly a miracle and I’m pretty sure millions of women suffering PCOS and insulin resistance will get pregnant thanks to these drugs.

If you made it this far, sorry for the long email. I feel strongly about these medicines and their life-changing effects.

I’m including a fun picture of my weight in chart form spanning 13 years of weight. I started logging my weight in 2013 all the way down, back up and then down to where I am today.

Best regards,

XXX

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First of two parts.