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Comment by annzabelle | Hacker News Reader

N of 1, but I had serious low drive/motivation side effects from Wegovy. Everything enjoyable became less enjoyable, from alcohol, to running, and after a couple of months, even getting out of bed. I lost weight slower than I had previously with old school calorie counting (most of which I have kept off to this day). Within a couple weeks of getting off it I was back to normal.

My conspiracy theory is that a lot of people must be getting this global lowered reward sensitivity from GLP-1s but are ignoring the negative sides of that effect because they like being skinny.

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I felt something like that affect, though not very pronounced, for the first couple weeks. Since then I've felt completely normal. Life is way more fun now.

One thing that colors how I view it is that I am more in the "would like to lose 15 lbs" space than the "needs to lose 50 lbs" space at this point in my life. I have a BMI of 27 and ran a half marathon right when I first tried Wegovy, and I already weigh 30 lbs less than I did at my 2021 peak. My A1c is 4.6. I actually recently reached out to my doctor about trying a different GLP-1 and she told me that given my labs and that I haven't been gaining weight she doesn't feel right prescribing me one.

So I am a lot more picky about side effects than I would be if I seriously needed to lose weight or had diabetes.

With a BMI of 27 why would you try GLP-1s at all? I would also be less forgiving of side effects if I were in that situation.

But my BMI was like 39, and now it is ~25. My blood test results the last couple of years have been phenomenal. All of the extra cardiac testing I've done suggests I managed to dodge a lot of the effects of being obese, which is just genetic luck (heart disease does not run in my family, most of my immediate ancestors lived well into their 90s and all of them died of something other than heart disease, even though some were fairly overweight).

I have played a little roulette with GLP-1s lately because I am curious, and found that at my current weight (5'11" or so and 175lb) seems to be where my body is willing to go, and that's about it. I stalled out pretty abruptly, and if I increase the dose all I get are uncomfortable side effects and no real weight loss -- even though the discomfort pushes my caloric intake well into the "cannot get enough vitamins and minerals" level. It's remarkable. I was once 165 naturally but 30 years ago, and that just isn't a realistic goal any more, so says my body. This is fine, I feel very good now. Well, when I'm on the maintenance dose ;-). Then I have no side effects, I just live a normal life eating normal amounts of healthy food and having a way easier time exercising than when I was heavy.

Honestly I was finding the last 15 lbs to be stubborn, and had a borderline mild sleep apnea test that meant my doctor offered it and my insurance would cover it. I also wanted to see what all the hype was about.

That's fair.

I forgot about sleep apnea. I was struggling with adjusting to CPAP, and never really succeeded. After losing a fair amount using tirzepatide, I did a repeat sleep test and my sleep doc gave me the green light to put the CPAP in storage.

In the end, a year after the borderline sleep apnea test, we optimized my thyroid medication dosage (I had hypothyroidism the whole time but my dose was too low) and I went on a multivitamin, and after a couple of months, the sleep issues that were why I'd gotten that test in the first place went away. And, it's easier to lose weight when my thyroid is properly treated.

I was beating my head against those sleep issues for years, and had multiple doctors sit down and tell me that I probably "just had a high sleep need." In the end, I'm not sure whether it was the thyroid or some vitamin deficiency (before the multivitamin I was on iron, C, and D separately), but it turned out to be very treatable.

>But my BMI was like 39, and now it is ~25. My blood test results the last couple of years have been phenomenal

If you’d lost the weight without GLP-1s, your blood test results would still have been phenomenal. Most of the effect you are seeing is the result of lowered bodyfat% through calorie deficit.

now, in your case calorie deficit comes from GLP1 use but in others case it can come from sustainable dieting which is little more tricky execute properly than just injecting a drug.

> If you’d lost the weight without GLP-1s

I've lost the weight several times over the last 30 years. The test results were never so dramatically improved. Your hypothesis may be wrong.

Caveat: I've not been on GLP-1s.

Sounds quite a bit like when I started the probiotics I've been on for quite a few many years now: When I started these ones, I actually started feeling worse than before. Ultimately though, after IIRC about two weeks of feeling worse than before, things got better.

I started out being lethargic all the time (in hindsight: way, way too many years, I just didn't put 2+2 together on multiple symptoms!). Migraine headaches from certain foods as well as any amount of alcohol and even non-alcoholic beer for example, essentially anything that produces histamines (which certain foods as well as alcohol consumption does).

After the probiotics "fought and won the battle" against whatever was inhabiting my intestines before that, I felt totally fine. No more lethargy. Could eat all the histamine rich foods in the world (Roquefort, here I come again, you're soooo tasty! Maybe with a glass of red wine too) and be fine. Never looked back. Life is way more fun now.

I might want to get on GLP-1s to not like alcohol and too much Roquefort now, while still not being lethargic, lol!

You're not the only person to report anhedonia. This shouldn't be downvoted.

> My conspiracy theory is that a lot of people must be getting this global lowered reward sensitivity from GLP-1s but are ignoring the negative sides of that effect because they like being skinny.

Possibly some of them could also be unintentionally countering the impacts through things like self-medicating with caffeine.

I have no personal experience with GLP-1s but suddenly quitting caffeine after decades of daily use was pretty eye-opening in terms of how much it was boosting my baseline mood. And I'm not talking about being cranky for a couple of days after quitting, I'm talking about a very noticeable sustained change from when I was a frequent caffeine user to when I stopped having it altogether.

Seconding this without straying too far from the topic.

My entire life I have been underweight and also ridiculously hooked on caffeine. At work I would easily go through 5-8 cups of coffee in a day.

I quit caffeine to become a parent a few years ago and suddenly I am able to put on fat and muscle so much easier.

I think the fact that 95% of our society consumes one of the best weight loss drugs (caffeine) anyway really skews a substantial portion of the data.

Speaking of which, nicotine is another effective weight loss drug. I have to wonder if some portion of the increase in median BMI (ignoring the morbidly obese) in America over the last 50 years is it becoming less socially acceptable to chain smoke.

Looks like it's typical to gain 5-10lbs when quitting smoking.

Edit: pulled up the data and there's been a 30lb increase in median weight in America, so (loosely guessing) the smoking effect is probably somewhere between 5 and 10% of that change.

> Speaking of which, nicotine is another effective weight loss drug.

Nicotine is a very useful drug that is sadly so very, very bad for you.

It has weight loss impacts, acts as a stimulant and is actually one of the better non-prescribed treatments for ADHD (as well as being super associated with schizophrenia).

After I got my ADHD diagnoses I noted that this was always called out in the literature, and I have been addicted to nicotine for the past 25 years or so (on a vape now, which appears to significantly reduce some of the bad side effects, but is still probably not good for me).

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