I've had trouble maintaining my weight since high school. If I eat "normally", I slowly gain weight, and if I eat nothing but a specific potato casserole, I slowly lose weight.

Recently, I hit a new high-record weight and decided it was finally time to do something more serious about it, so for the last month I've been taking the standard CICO diet advice. I finally realized that I should eat healthier, and eat significantly less. I work out slightly more. I cut out most high-fat foods and became strict about not eating after 6 pm.

Anyway, this is a post about my experience with retatrutide.

This is not a how-to article, so I'm not going to talk about where to get peptides or how to safely use them. See this article if you're into that sort of thing.

The Experiment

Retatrutide is a GLP-1 agonist similar to semaglutide (Ozempic), but which seems to cause more rapid weight loss.

It isn't FDA-approved yet, but you can buy it for experimental purposes. I forgot to pre-register my experiment, but my hypothesis was that if I took 2 mg^[1] of retatrutide per week, I would lose weight.

I also failed to register this experiment with an IRB. My doctor told me that losing weight would improve several of my health conditions, but GLP-1 drugs are only indicated with a BMI 0.5 units higher than mine.

So, I guess my experiment was highly unethical. Luckily it was privately funded and the subject is unlikely to sue me.

Effects

For a few days after my first injection, pretty much all food repelled me. I tried to take 50 g of protein powder every day to limit muscle loss, but found it very difficult to stomach.

Food has become less repellent over time, and I mostly get through my protein powder now, but I still find it hard to eat more than two-thirds of what I used to.

In terms of Axes of Hunger, I have much less of an appetite, sometimes experience minor / easily ignored hunger pangs, and don't seem to experience much emotional distraction from being hungry. I intellectually know when I should probably eat a meal, but can trivially ignore it if I'm busy and want to blog more.

I also find fatty food and alcohol much less tempting, although this might be because they exacerbate the side effects.

Over the first 30 days, I lost about 10 lbs and went down one belt size.

I was losing weight so fast initially that it was actually kind of concerning, so I forced myself to eat more. I assume the rapid weight loss was glycogen ("water weight"), since I still don't eat very much but weight loss has dropped to a less-concerning 1.5 lbs per week.

Side Effects

Muscle Loss?

I did some workouts to try to prevent muscle loss, including biking to work (3 days per week), a relatively hard 2 hour hike (once per week), two sets of ~15 pushups, and as many sets of 1-3 pullups as I remembered to do. I was very inconsistent about all of this.

I don't track my workouts very well, and I don't have any objective lean mass data, but:

• I do around the same number of pushups as I could 30 days ago.
• I can do more pullups (probably because they're 10% easier).
• Biking feels about the same.
• Hiking is terrible, but I think that's because of my heart rate and not because of muscle loss.

I doubt you could gain muscle with this much of a calorie deficit, but subjectively I feel just as strong as I was a month ago.

Heartburn

The most immediate side effect was heartburn, bad enough that I started taking omeprazole. It was a daily occurrence for about a week, but now it only seems to happen when I exercise really hard, eat late, or drink alcohol. I try to eat my last meal of the day around 5 pm so I have plenty of time to digest before bed, but 30 days in I can eat at normal times if I have to.

If I did this again, I would take omeprazole for the first week, then the morning after each injection for the second week.

Note: You should not take omeprazole longer than 14 days without talking to a doctor, since your body adapts to it.

Heart Rate

The most concerning side effect was my resting heart rate jumping up and my heart rate variability dropping. I found it significantly more uncomfortable to do cardio like running or hiking (although I found it easier to motivate myself to do moderate workouts).

If I did this again, I'd try tirzepatide, which seems to have less of an effect on heart rate.

Skin Sensitivity

For the first few weeks I'd experience a "tickling", sort of electric feeling from my clothes.

It was weird and occasionally distracting, but not really a problem, and went away by the end of the month.

Chills

I'm not sure if this was caused by the drug^[2], or the rapid weight loss, but I've turned into a person who freezes in slightly cold rooms. I wear much warmer pajamas, use more blankets, and don't wear shorts as often.

Unfortunately, I didn't measure this before starting, but my core temperature is actually slightly high, hovering around 99° F.

Injection Site Redness

Stabbing a needle into your body makes it upset[citation needed], so I usually get some redness and swelling the day after an injection.

For some reason I didn't get this for the first two weeks, but have had it consistently since. My symptoms are consistent with physical trauma and not infection, so it's annoying but not concerning. Being more careful and steadier with the needle seems to have helped.

Update: This kept getting worse and using a smaller needle didn't help, so I'm going to switch to once-weekly injections and also dilute the drug with significantly less reconstitution solution (20 mg / mL). I'll update if this fixes it.

Splitting Doses

I had a suspicion that the wild swings in drug concentration over the course of a week were making the symptoms worse, so I switched to 1 mg twice per week for the same total amount but more consistent levels. This subjectively seems to help, although it's annoying that twice the injections means twice the redness and swelling.

Update: As mentioned above, the injection site redness is annoying enough that I'm going to do once-weekly injections instad.

Other Effects

Some people think drugs like retatrutide have an effect on energy, but I disagree. It's just a coincidence that...

..I wrote one-third of the LessWrong posts I've ever written in the last month^[3]..

..and started exercising slightly more consistently..

..and finally finished that annoying project I was putting off at work..

..and even caught up on my TODO list.

It's weird because I actually do have a good reason for why I suddenly did each of these things: I was inspired by LessOnline and Inkhaven, it was nice out and I was more motivated by exercise to prevent muscle loss, and the midsummer planning/burnout season was over.

But it does seem kind of suspicious.

A Theory

If retatrutide did help, my guess is that the mechanism is removing distractions. Like I mentioned above, sometimes I'd be working on a post and notice I was getting hungry, then proceed to ignore it and continue writing for a few more hours.

I also find it easier to plan exercise. I don't like to exercise when I'm hungry, but I also don't like to exercise after a heavy meal. Conveniently, I'm never very hungry now, and haven't eaten a heavy meal in over a month.

Maybe the real akrasia was the hunger we had along the way?

Final Thoughts

So, do I recommend injecting yourself with experimental chemicals?

Absolutely not! Losing weight in this way is immoral without the oversight of an IRB, and no IRB would allow such an obvious conflict of interest, where the subject gains significant health improvements in exchange for participating. Also, on a more serious note, retatrutide raising your heart rate is annoying and mildly concerning.

But, maybe do talk to your doctor about an FDA-approved drug like tirzepatide if your weight is causing problems for you. This was way easier than any normal diet, worked better, and the side effects are all manageable, especially if you're prepared.

GLP-1 drugs are kind of magical.

1. ^{^}

   If I did this again, I'd start at a lower dose to minimize the side effects. Maybe 0.5-1 mg per week, then ramp up.

2. ^{^}

   Update from a month later: I think skin sensitivity from the drug is part of why I'm getting (noticeable) chills.

3. ^{^}

   This isn't because I just started writing here. I wrote my first post 9 years ago.