Results: In 51 408 patients (mean age 56.8 years, 48.9% male), GLP-1 RA use was associated with higher depression incidence versus SGLT2i use (17.0% vs. 14.8%; hazard ratio 1.09, 95% CI 1.04-1.14; p < 0.001), with an absolute risk difference of 2.2%. The association was stronger in adults ≥65 years (HR 1.15) and plateaued after approximately 6 months. In secondary analysis, GLP-1 RA use was associated with a lower rate of all-cause mortality (HR 0.74, 95% CI 0.63-0.88).
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Any hypothesis as to why this could be?
My best guess is that you become depressed because GLP1 force you into a calorie-restricted state.
if you don’t mind me asking, where are you sourcing from?
When you go on a GLP1 agonist you’re more likely to be a fatass, which tends to correlate with feeling depressed.
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But losing weight effortlessly should improve the fatass’s outlook on life. Being thin and fit makes me feel great. My weight bounces around and I have to struggle a bit to stay there. Honestly if it wasn’t an injection I’d probably be using a small dose.
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I experienced suicidal depression right after starting semaglutide, before it even had a real effect on calorie restriction. There must be something else. (I obviously quickly stopped semaglutide…)
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Three weeks in with semaglutide.
Still on entry level dose.
Weight & body fat
I’ll typically weigh myself first thing in the morning, then again after I’ve rehydrated.
On early morning weighing:
- 09/13/2025 - weight | body fat: 199 lbs | 21% (41.8 lbs)
- 10/04/2025 - weight | body fat: 195 lbs | 18% (35.1 lbs)
If I have calculated correctly, I’ve lost over 6 lbs of fat and gained muscle.
I have a Withings scale that gives me a relative measure of visceral fat levels. A bit dodgy, but this has dropped a bit too.
The percentages usually look even better when I’ve rehydrated, just haven’t gotten around to that this morning.
Diet
- Keto
- High fiber (2 tbs each of potato starch, inulin, and psyllium husk powder)
- Protein 150-200 grams per day
Clearly in caloric deficit, but easily maintained.
I do eat a couple of peaches every day.
Semaglutide hasn’t made me nauseous, but it does make me feel a bit odd. I kind of need to force feed myself protein.
strong text
Exercise
- HIT | Katalyst EMS twice per week
- Mobility and flexibility work almost daily
- Moderate walking (~7k steps per day)
Downside
- Resting heart rate increased from ~ 57 bpm to ~ 63 bpm.
- Sleep disruption
More on sleep…
Sleep protocol.
- Regular bed time, pretty aligned with chronotype.
- Ear plugs.
- Eye mask
- Cool room
- Very little water after 8 PM in the hope on not needing to wake to urinate through the night.
- No caffeine after 10 AM.
- Tracking (Oura ring and now Somnee)
My best nights before starting semaglutide had me up at least once, but usually twice. Nevertheless, I would usually fall back asleep in a reasonable amount of time.
Since starting at least twice.
I fall asleep readily and in the first 3 hours of sleep during which I typically get close to an hour of deep sleep. Since starting semaglutide:
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I’ll wake after 3 hours and don’t easily fall back to sleep.
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Eventually falling asleep I’ll wake again after another 3 hours or so, get up to urinate, and on returning to bed again don’t easily fall back to sleep.
This leaves me with maybe 5 1/2 vs 7 1/2 hours of sleep.
Not good. Hoping this will ease as I acclimate to the semaglutide.
While controversial, I’ve take to bi-phasic sleeping (naps in the afternoon).
Pretty easy to fall asleep, but I don’t really make up the sleep debt.
Currently working with my urologist to see if we can address the issue.
Just receive the 2nd generation Somnee. Theoretically, it should help falling back to sleep. I’ll report later on it in the technology thread. For now, I find it an interesting device with a dodgy app and poor documentation. Yet, I have some hope that it will help.
Thoughts and suggestions appreciated.
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Incase you are not aware, there are places that sell oral glp1’s now.
For me, I wish I could inject everything I take once a week and skip all pills :).
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There at many GLP1 receptors in the brain, and semaglutide is being studied for Parkinson and Alzheimer disease. No surprise that it can also mood, although the mechanism is still not clear.
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It could be that the fatass became one BECAUSE he was depressed, not the other way around.
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Our first encounters with food double as emotional soothing. Feeding and emotional regulation are indistinguishable, and that bond (can) persist. People living with overweight may use food more for mood regulation. GLP-1 agonists curb appetite and alter these emotion-regulation pathways. It’s like taking away a pacifier, there can be some crying before new soothing strategies develop.
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