Warning about a low probability event: adverse liver reaction to GLP-1 drug

[keangkong]

I wanted to warn folks about a low probability event: an adverse liver reaction to a GLP-1 drug.

For background, my doctor said that I most likely experienced a drug-induced-liver injury (DILI). I have no noticeable symptoms but do have ALT levels 10 times the upper limits or normal and also elevated AST and bilirubin levels. He doesn't know which drug is the cause but believes the most likely cause is Lipitor, which I've stopped taking along with retatrutide. Per doctor's order, I continue to take tirzepatide. (I'm a little skeptical that it's the Lipitor since I've been on Lipitor for 20 years. DILIs from Lipitor usually start much sooner although there have been other cases where the injury occurred much later).

As a result, I've been researching drugs I take. I found the articles below information about what medical journals believe to be liver problems caused by tirzepatide. I should emphasize that liver problems with tirzepatide are extremely rare (far less common than with Lipitor, for instance).

To research DILI by drug in general, the best source is probably LiverTox.

Abdullah, et al. (2024). Tirzepatide-Related Acute Liver Injury. Eur. J. Case Rep. Internal Med., 11(9), 004813 [24-year old female teacher; 6 months to onset].

Ahmed, et al. (2025). A Rare Case of Tirzepatide-Induced Hepatitis - Causality Assessment With the RUCAM Criteria. Annals Internal Med., 4(1) [female in her thirties; three months to onset].

Berihun, et al. (2023). A Rare Case of Tirzepatide-Induced Liver Injury. Am J. Gastroenterology, 118(10S), S2282 [37-year old woman; 2.5 months to onset]. This appears to be same person/incident described in Sohal, et al. (2024). A rare case of tirzepatide-induced hepatotoxicity. ACG Case Reps. J. 11(10), e01484.

LiverTox on Tirzepatide (C).

Phox, et al. (2025). Tirzepatide-Induced Liver Injury - A Rare Medication Side Effect. ACG Case Rep. J. 12(4), e01661 [76-year old female; eight weeks to onset].

Sohal, et al. (2024). A rare case of tirzepatide-induced hepatotoxicity. ACG Case Reps. J. 11(10), e01484 [37-year old female; 2 1/2 months to onset]. This appears to the same incident reported in Berihun, et al. (2023). A Rare Case of Tirzepatide-Induced Liver Injury. Am J. Gastroenterology, 118(10S), S2282.

 

[byefatlicia]

Thank you for sharing🙂

 

[clayd]

Thanks for the warning. Are these things that heal/repair themselves once the offender is eliminated?

best of luck figuring it out

 

[keangkong]

Are these things that heal/repair themselves once the offender is eliminated?

Usually.

best of luck figuring it out

Thanks.

 

[Mr. Blonde]

Is this something Tudca or NAC could help with? Anabolic users take these for liver support. But I hadn't heard of glp1s doing liver damage before.

 

[keangkong]

Is this something Tudca or NAC could help with? Anabolic users take these for liver support. But I hadn't heard of glp1s doing liver damage before.

GLP-1s rarely cause liver damage. Even in my case, the doctor believes Lipitor is the most likely cause.

I had never heard of tudca or NAC before. (I did look them up after seeing your post.) I'm not going to say whether I'd take them right now because I don't know yet. . I'm inclined to be cautious in what I take. If my blood results don't improve, I'll likely have a liver biopsy, a surgical procedure that is outpatient but will require that I be off work for two weeks.

 

[peptidepower77]

GLP-1s rarely cause liver damage. Even in my case, the doctor believes Lipitor is the most likely cause.

I had never heard of tudca or NAC before. (I did look them up after seeing your post.) I'm not going to say whether I'd take them right now because I don't know yet. . I'm inclined to be cautious in what I take. If my blood results don't improve, I'll likely have a liver biopsy, a surgical procedure that is outpatient but will require that I be off work for two weeks.

I wouldn't be so quick to dismiss it. There have been reports on Reddit of people having to quit Tirz or Reta for elevated liver enzymes too. Let us know what happens though, wishing you the best.

 

[Stone]

I've been on tirz and switched to reta a couple months ago. I'm only doing 1mg x Mon/Wed/Fri

Did my labs a couple weeks ago and the only thing out of place was higher level enzymes. Doc wanted me to do another set of labs a couple weeks later (which will be tomorrow morning). I don't have them in front of me one had went up double and the other was four times what it had been the last 10 or so years.

They weren't to a point he was really concerned, if they kept going up. I know one had been in the 20's and was 80 and he said unless it went to the 100's then 1000's it would be a problem we would need to dig into.

If I had to guess tirz/reta would probably be the cause but only speculation.

 

[peptidepower77]

My ALT was about 30 on Tirz. When Is switched to Reta it climbed to 50, the 60, then 70, then 90, then dropped to 70, then to 50, now back to 42. I think it's the glucagon component forcing the liver to burn fat. It stresses the liver out which is why it caused elevated liver enzymes. It's likely a net positive, but the liver compensates while it's adjusting and clearing liver fat I think.

 

[keangkong]

My ALT was about 30 on Tirz. When Is switched to Reta it climbed to 50, the 60, then 70, then 90, then dropped to 70, then to 50, now back to 42. I think it's the glucagon component forcing the liver to burn fat. It stresses the liver out which is why it caused elevated liver enzymes. It's likely a net positive, but the liver compensates while it's adjusting and clearing liver fat I think.

That seems right. Temporarily elevated liver enzymes not exceeding three times the upper limit of normal is not a big deal. It would not surprise me (assuming that reta or tirz is the case) if I could have stayed on reta and been fine. However, with numbers as high as mine have been, I was not willing to take that gamble without a doctor backing me up and saying that was a reasonable decision. I do know that my ALT was so high that it would have resulted in me being booted from the reta trial.

 

[keangkong]

I wouldn't be so quick to dismiss it. There have been reports on Reddit of people having to quit Tirz or Reta for elevated liver enzymes too. Let us know what happens though, wishing you the best.

I'm not actually dismissing reta or tirz at the cause. I stopped taking reta at my hepatologist's recommendation. I've continued to take tirz at the hepatologist's recommendation. I did want to emphasize that this is considered a low probability event because I didn't want to panic everyone else. But I myself am panicking. Maybe not technically. But I'm worried. I do have a blood test scheduled for next Tuesday; I'll likely get the results the next day. Taking only tirz, I'm rapidly gaining weight. Being without reta makes me appreciate the effortless way I ate the right amount. I worry that I'll have to get off these drugs for a few months and that I'll need a liver biopsy. I'm not seriously worried about experiencing major liver damage because my hepatologist scheduled my next appointment three months from now and he has conducted several blood tests looking for different kinds of liver damage. Still I hate being off reta.

 

[Loosingit]

My ALT was about 30 on Tirz. When Is switched to Reta it climbed to 50, the 60, then 70, then 90, then dropped to 70, then to 50, now back to 42. I think it's the glucagon component forcing the liver to burn fat. It stresses the liver out which is why it caused elevated liver enzymes. It's likely a net positive, but the liver compensates while it's adjusting and clearing liver fat I think.

How often were you having your tests done when you switched to Reta?

 

[Needsalife]

🙏 for you. Thank you for sharing. My liver enzymes were elevated at 245 lbs. After a year of Tirz and 85 lbs lighter, my liver enzymes are perfect. My doc is doing bloodwork every 6 months. The above hypothesis about Reta’s work on reducing liver fat is an interesting take. I’m with you, your large increase is concerning, and will hopefully go down with your disuse of Reta. I’m sure you’re anxious. Good luck.

 

[rsmith]

I'm not actually dismissing reta or tirz at the cause. I stopped taking reta at my hepatologist's recommendation. I've continued to take tirz at the hepatologist's recommendation. I did want to emphasize that this is considered a low probability event because I didn't want to panic everyone else. But I myself am panicking. Maybe not technically. But I'm worried. I do have a blood test scheduled for next Tuesday; I'll likely get the results the next day. Taking only tirz, I'm rapidly gaining weight. Being without reta makes me appreciate the effortless way I ate the right amount. I worry that I'll have to get off these drugs for a few months and that I'll need a liver biopsy. I'm not seriously worried about experiencing major liver damage because my hepatologist scheduled my next appointment three months from now and he has conducted several blood tests looking for different kinds of liver damage. Still I hate being off reta.

Consider researching via an ABAB design where you are off GLPs 1 month (test enzymes), on 1 month (test enzymes), off 1 month (test enzymes), on 1 month (test enzymes).

Believe it or not, this is a very valid way to research a substance via Single Subject design. If the Tirz is causing the problem, you will know with near certainty. You could do the same thing with your Lipitor. Whatever you are testing though, try to keep everything else constant (e.g., if you're testing the Tirz via ABAB, keep taking the Lipitor the whole time).

FWIW, I'm a scientist. I know stuff 🤣

I do wish you the best and hope you get to the bottom of this so you can sleep well and be healthy.

 

[peptidepower77]

How often were you having your tests done when you switched to Reta?

I have been doing lots of other tests for long covid, some weekly, so I tacked on liver and insulin tests pretty much weekly since I started.