Peptide fatigue after almost a year on GLP-1s and Retatrutide — what would you do?

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guster

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After nearly a year on GLP-1s and now Retatrutide, my experience feels worth sharing.

Mounjaro was where I started around last year, at about 105 kg and roughly 32% body fat. The goal was simple: lose fat, get healthier, and eventually get lean enough to finally see my abs.

For about 8 months Mounjaro (tirzepatide) was what I stayed on, working my way up to 10 mg. Honestly, side effects were almost zero the entire time. My relationship with food was completely changed, and a huge amount of weight came off.

About 2 months off Mounjaro, then on to Retatrutide. Mounjaro stopping working was not the main reason. It was simply too expensive at around €600 per month, and the added glucagon pathway that Retatrutide offers was very interesting to me.

Retatrutide was started very cautiously:

  • Week 1: Monday 0.5 mg + Wednesday 0.5 mg
  • Week 2: Monday 1 mg + Wednesday 1 mg
  • Week 3: Monday 2 mg + Wednesday 1 mg
  • Week 4: 4 mg, once weekly
  • Several weeks spent on 4 mg
  • Later raised to 6 mg weekly

One surprise: the crazy appetite suppression that many people describe never really showed up for me. Even on 6 mg, those “I can’t eat anything” moments don’t happen. Weight kept dropping anyway.

As of today I sit at 75 kg, which is around 30 kg lost from where I started.

Fat loss has not been the biggest downside. Muscle loss has. After such a long cut I definitely feel flatter, smaller, and honestly just tired. The first 20 kg came off easily compared to trying to lose the last bit of belly fat.

KLOW80 also ran for about 3 months. How much it contributed I am honestly not sure. Recovery and skin quality may have benefited, but separating those effects from everything else is difficult, so stopping it for now is the decision.

Tesamorelin got started recently, because the goal has completely changed. Losing as much weight as possible is no longer the aim. Preserving muscle, and hopefully regaining some while dropping the last bit of fat, is what I want.

The problem is that peptide fatigue may be setting in. Not physically, but mentally. Injecting things is honestly getting tiring. Even though they are only 4 mm insulin needles, I still hate needles, and every new peptide means another injection.

Mentally I am also stuck in a weird place. 75 kg is all I weigh now, which for me is pretty light. Some fat and loose skin remains around my lower stomach, and my confidence is absolutely destroyed by it. My brain gets tricked into thinking, “Just lose one more kilo.” Deep down I know that is probably the wrong move. Lighter is not what I need. More muscle is what I need.

Which is why the focus is shifting toward building muscle rather than chasing the scale. Tesamorelin is what I am using at the moment, and Ipamorelin is under consideration since I already have it. Completing the GH axis with CJC-1295 (no DAC) has been thought about too. Realistically though, compared to something like TRT or HGH, these peptides will probably only give a relatively small benefit.

The funny thing is, if that road ever gets taken, manning up and considering TRT is probably all I need. The irony: needles terrify me. Mentally preparing myself for a tiny 4 mm peptide needle is already required, so TRT feels like a huge step.

Right now fatigue is simply my biggest problem. Around 30 kg down, and my body feels like it has had enough. Gym motivation is nowhere near what it used to be. Going still happens, but not with the same intensity, because most of the time I just feel exhausted. Part of that is probably the long calorie deficit rather than the peptides themselves, I know.

Things like MOTS-c and SS-31 have also been looked at for potential energy help, but then I catch myself thinking… am I really about to inject five different peptides every week just to chase a few extra percent?

So I am curious what you guys would do in my position.

Would you:

  • Keep cutting until that last bit of belly fat is gone?
  • Slowly raise calories and shift focus to building muscle?
  • Stay on Tesamorelin and add Ipamorelin?
  • Drop all the extra peptides and just recover from such a long cut?

Hearing from people who have actually gone through this phase after major weight loss would be really appreciated.

Male, 35

178cm

A fair bit of muscle is still there, because working out on and off for 5 years has been the routine

:::
 
The next step should be a full bloodwork panel, to check whether anything is outside the normal range and might be triggering or worsening the fatigue?

When you're dealing with problems like these and haven't even had bloodwork done, I wouldn't just start throwing random things into the mix
 
guster said:

After nearly a year on GLP-1s and now Retatrutide, my experience feels worth sharing.

Mounjaro was where I started around last year, at about 105 kg and roughly 32% body fat. The goal was simple: lose fat, get healthier, and eventually get lean enough to finally see my abs.

For about 8 months Mounjaro (tirzepatide) was what I stayed on, working my way up to 10 mg. Honestly, side effects were almost zero the entire time. My relationship with food was completely changed, and a huge amount of weight came off.

About 2 months off Mounjaro, then on to Retatrutide. Mounjaro stopping working was not the main reason. It was simply too expensive at around €600 per month, and the added glucagon pathway that Retatrutide offers was very interesting to me.

Retatrutide was started very cautiously:

  • Week 1: Monday 0.5 mg + Wednesday 0.5 mg
  • Week 2: Monday 1 mg + Wednesday 1 mg
  • Week 3: Monday 2 mg + Wednesday 1 mg
  • Week 4: 4 mg, once weekly
  • Several weeks spent on 4 mg
  • Later raised to 6 mg weekly

One surprise: the crazy appetite suppression that many people describe never really showed up for me. Even on 6 mg, those “I can’t eat anything” moments don’t happen. Weight kept dropping anyway.

As of today I sit at 75 kg, which is around 30 kg lost from where I started.

Fat loss has not been the biggest downside. Muscle loss has. After such a long cut I definitely feel flatter, smaller, and honestly just tired. The first 20 kg came off easily compared to trying to lose the last bit of belly fat.

KLOW80 also ran for about 3 months. How much it contributed I am honestly not sure. Recovery and skin quality may have benefited, but separating those effects from everything else is difficult, so stopping it for now is the decision.

Tesamorelin got started recently, because the goal has completely changed. Losing as much weight as possible is no longer the aim. Preserving muscle, and hopefully regaining some while dropping the last bit of fat, is what I want.

The problem is that peptide fatigue may be setting in. Not physically, but mentally. Injecting things is honestly getting tiring. Even though they are only 4 mm insulin needles, I still hate needles, and every new peptide means another injection.

Mentally I am also stuck in a weird place. 75 kg is all I weigh now, which for me is pretty light. Some fat and loose skin remains around my lower stomach, and my confidence is absolutely destroyed by it. My brain gets tricked into thinking, “Just lose one more kilo.” Deep down I know that is probably the wrong move. Lighter is not what I need. More muscle is what I need.

Which is why the focus is shifting toward building muscle rather than chasing the scale. Tesamorelin is what I am using at the moment, and Ipamorelin is under consideration since I already have it. Completing the GH axis with CJC-1295 (no DAC) has been thought about too. Realistically though, compared to something like TRT or HGH, these peptides will probably only give a relatively small benefit.

The funny thing is, if that road ever gets taken, manning up and considering TRT is probably all I need. The irony: needles terrify me. Mentally preparing myself for a tiny 4 mm peptide needle is already required, so TRT feels like a huge step.

Right now fatigue is simply my biggest problem. Around 30 kg down, and my body feels like it has had enough. Gym motivation is nowhere near what it used to be. Going still happens, but not with the same intensity, because most of the time I just feel exhausted. Part of that is probably the long calorie deficit rather than the peptides themselves, I know.

Things like MOTS-c and SS-31 have also been looked at for potential energy help, but then I catch myself thinking… am I really about to inject five different peptides every week just to chase a few extra percent?

So I am curious what you guys would do in my position.

Would you:

  • Keep cutting until that last bit of belly fat is gone?
  • Slowly raise calories and shift focus to building muscle?
  • Stay on Tesamorelin and add Ipamorelin?
  • Drop all the extra peptides and just recover from such a long cut?

Hearing from people who have actually gone through this phase after major weight loss would be really appreciated.

Male, 35

178cm

A fair bit of muscle is still there, because working out on and off for 5 years has been the routine

:::
Click to expand...
Nice work on the progress you've made with your weight so far!

If injections bother you to that degree, stacking a pile of daily pins on top probably won't do your mental fatigue any favors.

Exercise is what builds muscle; abs are made in front of the fridge. Peptides can give you support, but don't count on miracles. So if the remaining fat is what you want gone, keep yourself in a deficit. Tesa is a solid option when the goal is abdominal fat loss.

Don't over estimate the muscle loss, a lot comes from your liver apparently.




Effects of GLP‐1 Receptor Agonists on Muscle Mass, Strength, and Quality in MASLD: A Systematic Review - PMC



GLP‐1 receptor agonists (GLP‐1RAs) promote significant weight loss, but their impact on muscle mass, strength, and quality in metabolic dysfunction–associated steatotic liver disease (MASLD), a condition prone to muscle impairment, remains ...

4d13c41cbc0409fb932089618e379d69d6e07846fc324487242c1d77d1bad140.png



pmc.ncbi.nlm.nih.gov

I don't know your age but TRT is a subscription for life.
 
Sounds a lot like my situation, though for me it isn't a needle phobia—it's that I'd rather just brush my teeth and crawl into bed than jab myself 1 or 2 times, haha—and I'm also on TRT. I tend to tie way too much of my self-worth to how physically capable I am. Missing lifts and having to drop the weight sent me into a depression. What helped me most was raising my calories and building my strength back up, giving it time to level out, and only then going after the leftover fat.
 
guster said:

After nearly a year on GLP-1s and now Retatrutide, my experience feels worth sharing.

Mounjaro was where I started around last year, at about 105 kg and roughly 32% body fat. The goal was simple: lose fat, get healthier, and eventually get lean enough to finally see my abs.

For about 8 months Mounjaro (tirzepatide) was what I stayed on, working my way up to 10 mg. Honestly, side effects were almost zero the entire time. My relationship with food was completely changed, and a huge amount of weight came off.

About 2 months off Mounjaro, then on to Retatrutide. Mounjaro stopping working was not the main reason. It was simply too expensive at around €600 per month, and the added glucagon pathway that Retatrutide offers was very interesting to me.

Retatrutide was started very cautiously:

  • Week 1: Monday 0.5 mg + Wednesday 0.5 mg
  • Week 2: Monday 1 mg + Wednesday 1 mg
  • Week 3: Monday 2 mg + Wednesday 1 mg
  • Week 4: 4 mg, once weekly
  • Several weeks spent on 4 mg
  • Later raised to 6 mg weekly

One surprise: the crazy appetite suppression that many people describe never really showed up for me. Even on 6 mg, those “I can’t eat anything” moments don’t happen. Weight kept dropping anyway.

As of today I sit at 75 kg, which is around 30 kg lost from where I started.

Fat loss has not been the biggest downside. Muscle loss has. After such a long cut I definitely feel flatter, smaller, and honestly just tired. The first 20 kg came off easily compared to trying to lose the last bit of belly fat.

KLOW80 also ran for about 3 months. How much it contributed I am honestly not sure. Recovery and skin quality may have benefited, but separating those effects from everything else is difficult, so stopping it for now is the decision.

Tesamorelin got started recently, because the goal has completely changed. Losing as much weight as possible is no longer the aim. Preserving muscle, and hopefully regaining some while dropping the last bit of fat, is what I want.

The problem is that peptide fatigue may be setting in. Not physically, but mentally. Injecting things is honestly getting tiring. Even though they are only 4 mm insulin needles, I still hate needles, and every new peptide means another injection.

Mentally I am also stuck in a weird place. 75 kg is all I weigh now, which for me is pretty light. Some fat and loose skin remains around my lower stomach, and my confidence is absolutely destroyed by it. My brain gets tricked into thinking, “Just lose one more kilo.” Deep down I know that is probably the wrong move. Lighter is not what I need. More muscle is what I need.

Which is why the focus is shifting toward building muscle rather than chasing the scale. Tesamorelin is what I am using at the moment, and Ipamorelin is under consideration since I already have it. Completing the GH axis with CJC-1295 (no DAC) has been thought about too. Realistically though, compared to something like TRT or HGH, these peptides will probably only give a relatively small benefit.

The funny thing is, if that road ever gets taken, manning up and considering TRT is probably all I need. The irony: needles terrify me. Mentally preparing myself for a tiny 4 mm peptide needle is already required, so TRT feels like a huge step.

Right now fatigue is simply my biggest problem. Around 30 kg down, and my body feels like it has had enough. Gym motivation is nowhere near what it used to be. Going still happens, but not with the same intensity, because most of the time I just feel exhausted. Part of that is probably the long calorie deficit rather than the peptides themselves, I know.

Things like MOTS-c and SS-31 have also been looked at for potential energy help, but then I catch myself thinking… am I really about to inject five different peptides every week just to chase a few extra percent?

So I am curious what you guys would do in my position.

Would you:

  • Keep cutting until that last bit of belly fat is gone?
  • Slowly raise calories and shift focus to building muscle?
  • Stay on Tesamorelin and add Ipamorelin?
  • Drop all the extra peptides and just recover from such a long cut?

Hearing from people who have actually gone through this phase after major weight loss would be really appreciated.

Male, 35

178cm

A fair bit of muscle is still there, because working out on and off for 5 years has been the routine

:::
Click to expand...

40 years old, 187cm tall. Each week I inject 18mg of Reta, .25mg of Sema, and 150mg of Test C — that's 7 shots total. Side effects are essentially absent, and I'm dropping roughly 1% of my body weight weekly. DEXA scans show lean mass has held up remarkably well after the first 20lb came off (my baseline wasn't captured until 49 days into peptides because of scheduling) — under 2lb of lean mass gone. Scan number 5 lands this Monday, and I figure there may be some regression. My job involves a fair amount of physical activity, and I've never really done any serious weight training in my entire life.

Starting out at 282lb (128kg), my first target was 200lb (91kg). Right now I'm 207lb (94kg), just under 31 weeks in — a 27% reduction. A few months back I got the notion that a more ambitious aim would be to catch even a hint of abs, since I genuinely can't recall ever having seen them on myself. Going by DEXA results and standard body fat ranges, abs would require getting to 180-190lb, so I've set a new target of 182lb — a neat 100lb total loss — even though I doubt I'll see abs at 190lb anyway.

Not quite what you were asking, but my read is that your fatigue mostly comes from the effort you're putting in not producing the picture you had in mind by now. That letdown is coloring how you see the process and your results, which makes the whole business of injecting yourself feel like more of a chore. Fixing that means shifting how you look at things, reframing, finding victories that don't come from the mirror (the kind of non scale victories people talk about on social media).

I got somewhat annoyed that my waist wasn't shrinking the way I expected — I wasn't back in my heaviest pants, but I also wasn't getting trimmer despite having dropped 40-60lb or whatever the figure was. Then a month or two later, suddenly it felt like every piece of clothing I owned was enormous, like I was wearing sacks. Stuff I'd purchased just a few months earlier already fit terribly... "hmm, maybe I shouldn't go wild buying clothes at this stage, my final shirt size may be a large and my pants might be a 32"."

My advice would be to get bloodwork done — among other things to check your test levels (for TRT), your overall profile, and any shortages in vitamins, minerals, hormones, etc. For me, the data itself is another kind of victory.

Your flag shows the US, but you speak in kg... are you stateside or abroad?
 
Before GLP-1s became standard, people typically ran a yearly pattern of cutting and bulking in order to add muscle. Maybe what your body wants right now is a bulking phase: eat with some enjoyment and put on muscle, since you already know you can do a clean cut later.
 
Nice work on the progress you've made so far. I'm a woman, and peptide fatigue isn't something I deal with. That said, needles absolutely terrify me — to an embarrassing degree — and right now I follow an oral protocol that helps me with energy, focus, and an overall feeling of well-being.

I understand why poking yourself daily would get old. Whenever I'm even slightly dehydrated, the pinprick stings more. The needles I use are the tiniest kind. So drink enough water. A nurse mentioned to me a few years back that when you're dehydrated, shots and blood draws tend to hurt more or at least feel more noticeable.

Another suggestion: get labs done so you know your health is on track. After you get the all clear, an oral protocol for energy could be worth looking into. I'm wrapping up an NR/NMN cycle and the improvements have been clear. At 35, I have no idea what it would do for you. I'm further from 35 than 65. Maybe there are oral options out there that could help your energy and well-being.

Whichever path you choose, best of luck!
 
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