There's a poor man's Ozempic: metformin. It causes weight loss, and they seem to have figured out why. It stimulates the production of the signaling molecule "Lac-Phe" (N-lactoyl phenylalanine), which is normally produced in cells after high intensity exercise, and reduces appetite.

Metformin is a small, simple molecule that has long fallen out of patent, and is available very cheaply.

https://en.wikipedia.org/wiki/Lac-Phe

https://med.stanford.edu/news/all-news/2024/03/metformin-wei...

https://www.nature.com/articles/s42255-024-00999-9

Metformin has been the 1st choice for treatment of type 2 diabetes for decades. Countless millions have taken it daily for many years. Although I’m sure some lose weight taking the impact is not near as significant or wide spread as glp-1s. I have taken it for 20 years and never lost weight while on it. If there was significant weight loss across a large range of those taking it you would have heard a lot more about metformin being used for weight loss. I have taken Mounjaro since February and have experienced significant weight loss and my A1C has fallen to 5.3 which is significantly lower than on metformin alone or in combination with other type 2 medications.

My personal experience with metformin was it didn't cause weight loss, until I deliberately also tried diet (< 100 g net carbs per day) and exercise (~4 miles walking/day). That ended up being much easier to stick to than I had previously found it to be, and has caused me to slowly but steadily lose 25 pounds since May.

That reads to me that you have lost weight due to a combination of diet and exercise. Not necessarily metformin.

The key point was that it was very weirdly easy, compared to previous efforts, and I credit metformin (1000 mg/day) for that.

Also worth remembering that Metformin has an even higher GI distress side effect rate than GLP-1 drugs. Like, probably most people that take it get some bad GI side effects. It's not a great replacement for GLP-1 drugs.

The only significant effect I've noticed is some constipation, and that's solved by psyllium fiber supplements (not the ones that also contain a separate laxative, mind you). Taken in capsule form these have no effect on taste or texture of food or drink.

I'm glad side effects are mild for you, but obviously a single anecdote doesn't contradict data from millions of other users.

Yes, of course. I wouldn't want to misrepresent a personal anecdote as anything more than what it is.

While metformin is cheaper, I find that only fairly wealthy "longevity" maximizers have heard of it.

Also, it's far less effective than GLP1 RAs at weight loss, which is what most people want.

Unfortunately, Metformin gives me a brain fog that isn’t acceptable while having an engineering role. Maybe it has an interaction with Vortioxetine, I don’t know.

Welp, water is wet.

It won't be up to Novo Nordisk to reduce the cost of GLP1 RAs -- it will be up to other entrants into the market (that said, there are worryingly few), and huge companies taking up manufacturing of GLP1s and similar compounds.

At this point, companies partnering with compounding pharmacies might hit mainstream (more than it already has) and be the go-to way to get GLP1 RAs.

There's already a Liraglutide (Victoza/Saxenda) generic:

https://glp1.guide/content/victoza-generic-hits-the-market

Though I've seen some anecdotal reports that the generic was worse than regular Victoza.