#506

Risk of depression with GLP-1 receptor agonists use in overweight or obese adults with type 2 diabetes: A new-user, active-comparator cohort study 2025

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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#507

Any hypothesis as to why this could be?

#508

My best guess is that you become depressed because GLP1 force you into a calorie-restricted state.

#509

if you don’t mind me asking, where are you sourcing from?

#510

When you go on a GLP1 agonist you’re more likely to be a fatass, which tends to correlate with feeling depressed.

1 Like
#511

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.

3 Likes
#512

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…)

3 Likes
#513

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.
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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:

  • I’ll wake after 3 hours and don’t easily fall back to sleep.

  • 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.

3 Likes
#514

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 :).

6 Likes
#515

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.

1 Like
#516

It could be that the fatass became one BECAUSE he was depressed, not the other way around.

2 Likes
#517

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.

5 Likes
#518

Amateur Athletes Are Turning to Ozempic to Raise Their Game (WSJ)

Runners, cyclists and other fitness enthusiasts say weight-loss drugs give them a performance edge, despite potential risks

Amanda Rodriguez felt exceptionally proud as she ran the Chicago Marathon last fall. She also felt a touch weighed down.

With other races on the horizon, she decided to go back on tirzepatide, the active ingredient in popular diabetes and weight-loss drugs Mounjaro and Zepbound. She had used it before to take off some excess weight. Now she wanted to lose more to improve her running performance.

“My body just feels stronger,” says Rodriguez, 30, who has since lost 20 pounds while maintaining her diet and training schedule. She has also shaved a minute from her 5-kilometer time and completed her first ultramarathon.

Since Ozempic burst into the culture, medical researchers have discovered the drug and its cousins might offer wide-ranging health benefits, including curbing addictions and battling the aging process.

Now a burgeoning community of runners, cyclists and other sports and exercise enthusiasts are taking the weight-loss drugs in the hopes of gaining a performance edge. For members who are on the medications, gym operator Equinox has even created a personalized “GLP-1 protocol” training program that focuses on muscle-building and retention.

…

Dr. Richard Isaacson, a preventive neurologist, says he has recommended microdosing—taking a fraction of the regular dose—for some patients who are eager to optimize health and physical performance. One is a former Olympic gold medalist.

“We tried to see what was the minimal dose that he could tolerate without losing any more weight,” says Isaacson of the former Olympian, who had already been on a new diet and nutrition regimen. Over months, the athlete gained muscle, improved his VO2 max, a measure of aerobic capacity, and lowered his risk for neurodegenerative disease. “Everything about his everything improved.”

Read the full article: Amateur Athletes Are Turning to Ozempic to Raise Their Game

6 Likes
#519

Has anyone here switched from tirzepatide to retatrutide? I want to try it out and am thinking about starting on the 4mg dose. Since I’ve been using 5-7.5mg tirzepatide this dose should be roughly equivalent, correct?

1 Like
#520

I wouldn’t do that. Remember reta is a glucagon agonist while tirz isn’t, so you’d be getting the full glucagon effect of 4mg reta, which could potentially cause a heart arrhythmia for instance. Why the rush?

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#521

Where and how would you get it?

#522

Almost 5 weeks since starting semaglutide

Dose increased to 0.40 mg per week last Saturday.

Semaglutide hasn’t made me nauseous, but it continues to make me feel odd.
Same diet as previously reported.

Now the problems…

No acclimation

I clearly have not acclimated to semaglutide.

  • Sleep: Stepping up the dose to 0.40 mg made everything to do with sleep even worse (getting dangerously bad).

  • Heart rate: It also further raised my resting heart.

I reached out to HIMS to get advice.

Anyone with any kind of brain activity would have found the HIMS responses to my questions about sleep disruption and heart rate incompetent, unprofessional, and contradictory.

When I pointed out the discrepancies in their responses, they dropped me, closed my account and refunded my 6 month prescription.

No review or discussion offered to step back titration or look at anything internally.

This seems like a red flag that makes me wonder if I actually got semaglutide. HIMS markets compounded semaglutide so I wonder if I got a bad or contaminated batch.

Won’t find out now.

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It should get out of my system over the next week or so.
Hopefully my sleep will improve and my heart rate revert to previous levels.

Retatrutide

Reviewing Cremieux Recueil site on peptides and DIYing reconstitution.
Reports suggest that Retatrutide has fewer side effects.

Any experience with this welcome.

1 Like
#523

What we did when we switched from Tirz to Reta was a blend 50/50 Tirz and Reta and a slightly lower dose. Went down from 3.5 to 3.0 weekly. Second month we went 3.0 Reta.

Worked just dandy, no issues and we continued to lose at that dose and reached our goal weights. After a few months we dropped the dose again to see if we would go up, but we stayed the same at 2.5mg Reta and have been on that dose for over a year now.

I’ve had more than a few clients do the exact same thing to switch as I feel the Reta is a better maintenance product.

2 Likes
#524

Acclimation seems to not mean what is intended :slight_smile:

My experience is that it take 6 months to be fully acclimated. Yes the first month is the “acclimation” period but people still experience abnormal feelings the second and third.

Once you get past 6 months it is the new normal, both from a mental and physical aspect. It will not be the old normal so acclimation does not mean you feel like you did before GLP1, it means you are adapting to a new normal.

#525

I don’t think I could last through 6 months of sleep disruption.
Any strategies to address the issue?