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

[rsmith]

What am I missing? Why are you surprised by your lipids increasing when you stopped a lipid lowering medication?

Since starting GLPs and the like (e.g., cagri), I've been taken off of 2 hypertensives and had another one reduced by 2/3. Blood pressure has dropped and labs are improving dramatically as well. So the triple increase in LDL was somewhat of a surprise although it's likely a "rebound" effect rather than anything to worry about. The Survo I'm titrating up at present will hopefully bring that back down via the glucagon component.

 

[keangkong]

Am I correct that the blood testing results below, along with the dates of drug stops and starts, indicates that reta is likely causing liver problems? By the way, I don't plan on resuming Lipitor (atorvastatin) since I already had elevated enzymes while on it. I intend to speak with my cardiologist about pitavastatin, a statin that is less likely to cause liver problems. The rapid decline in liver enzymes after I stopped taking reta and Lipitor looks good. However, the rapid rise in liver enzymes after I resumed reta (at a tiny dose) look bad. These results are troubling since tirz alone was not getting me to a weight that I wanted to be. Still a slightly heavier me is better than a messed up liver.

 

[rsmith]

Am I correct that the blood testing results below, along with the dates of drug stops and starts, indicates that reta is likely causing liver problems? By the way, I don't plan on resuming Lipitor (atorvastatin) since I already had elevated enzymes while on it. I intend to speak with my cardiologist about pitavastatin, a statin that is less likely to cause liver problems. The rapid decline in liver enzymes after I stopped taking reta and Lipitor looks good. However, the rapid rise in liver enzymes after I resumed reta (at a tiny dose) look bad. These results are troubling since tirz alone was not getting me to a weight that I wanted to be. Still a slightly heavier me is better than a messed up liver.

View attachment 8993

It's too early to tell if Reta is your problem. Take it for at least 3 more weeks.

Also and importantly, since you're also still taking Tirz, it might be the Tirz X Reta interaction that is causing the liver enzymes to go up. Only way to know it to stop the Tirz, continue the Reta solo and see what happens over at least 1 month. Please keep us up to date.

 

[keangkong]

It's too early to tell if Reta is your problem. Take it for at least 3 more weeks.

Also and importantly, since you're also still taking Tirz, it might be the Tirz X Reta interaction that is causing the liver enzymes to go up. Only way to know it to stop the Tirz, continue the Reta solo and see what happens over at least 1 month. Please keep us up to date.

I didn't follow your good advice. Instead I stopped reta again.

After reading some of the case reports from LiverTox after I spoke to you and had again stopped reta, I realized that there is a weirdness and almost randomness to how liver enzyme values change. To know whether the changes are significant enough to show that something is or is not a likely or probable cause of liver injury, I need to use the RUCAM calculator, the tool most often employed by researchers in determining whether something has caused a drug induced liver injury.

The reason I didn't follow your advice and keep taking the retatrutide is that I was worried about my liver. If I had a doctor advising me who would say that it would be fine to keep taking reta, I would have done so. But my hepatologist is not such a person even though he previously (with less data that I showed you) concluded that reta is probably not the cause of the elevated enzymes. I plan on staying off the retatrutide and the Lipitor until my liver enzyme levels are completely within the normal zone. That might not ever happen since my liver enzymes have been at least somewhat elevated since 2011, when my record of liver enzyme tests begins. However, I suspect being off of both Lipitor and retatrutide, there is at least a 50% chance of obtaining normal liver enzymes. If the liver enzymes return completely to normal, I'll restart reta. I'd stay on it unless any liver enzymes rose to a level of three times the upper limit of normal or higher, or unless I experienced sustained elevated liver enzymes even if below three times the upper limit of normal. In this post, I used the term "liver enzymes" to mean actual liver enzymes or bilirubin, which is not a liver enzyme, I think.

The technical information I provided may convince some that I know what I'm talking about. I am an excellent researcher. However, my Achille's heel is that I know very little about the hard sciences. Without a background in what I write about, it's quite easy for me to make mistakes when writing about things about which I do not know.

 

[MsGizmo]

Am I correct that the blood testing results below, along with the dates of drug stops and starts, indicates that reta is likely causing liver problems? By the way, I don't plan on resuming Lipitor (atorvastatin) since I already had elevated enzymes while on it. I intend to speak with my cardiologist about pitavastatin, a statin that is less likely to cause liver problems. The rapid decline in liver enzymes after I stopped taking reta and Lipitor looks good. However, the rapid rise in liver enzymes after I resumed reta (at a tiny dose) look bad. These results are troubling since tirz alone was not getting me to a weight that I wanted to be. Still a slightly heavier me is better than a messed up liver.

I assume that all those tests happened in conjunction to doctor visit .. is it possible that there might be matching weigh-ins to see how your weight loss plays into it?

* For the record I am absolutely NOT trying to imply that you are making the wrong choice in stopping reta or down playing the seriousness of potential liver damage. As a person who is also taking reta I want a more complete picture of the risks I might be taking.

 

[LeadFitz]

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.

I don't have a definitive yes, but I always take Tudca when administering anything exogenous, its for peace of mind.

 

[keangkong]

I assume that all those tests happened in conjunction to doctor visit .. is it possible that there might be matching weigh-ins to see how your weight loss plays into it?

* For the record I am absolutely NOT trying to imply that you are making the wrong choice in stopping reta or down playing the seriousness of potential liver damage. As a person who is also taking reta I want a more complete picture of the risks I might be taking.

The majority of visits occurred near a doctor visit. A few did not. I'm not going to try to hunt down the weights for the majority of the time period involved because that would mean searching through countless records online, a process that would take several hours.

There are no confirmed cases of reta hepatoxicity in the medical literature.

I have found a few anecdotal, social media reports of possible problems with reta involving liver injury:

https://www.reddit.com/r/RetatrutideTrial/comments/1cijeva/have_to_return_for_followup_bloodwork

View: https://www.reddit.com/r/RetatrutideTrial/comments/1cijeva/have_to_return_for_followup_bloodwork/?share_id=fExEuwoJVeab6RUgPo2qv&utm_content=1&utm_medium=android_app&utm_name=androidcss&utm_source=share&utm_term=1

https://www.reddit.com/r/RetatrutideTrial/comments/1ecn6ll/finally_restarting

View: https://www.reddit.com/r/RetatrutideTrial/comments/1ecn6ll/finally_restarting/


https://threadreaderapp.com/thread/1961047954984452346.html

None of those posts are convincing evidence that reta caused the injury.

Since I wrote my prior post, I learned more about liver injury and how test results can jump around. I know that using the Roussel Uclaf Causality Assessment Method (RUCAM) in Drug Induced Liver Injury does not provide a strong answer that my liver injury was or was not caused by the reta.

It should be noted that drug-induced liver injuries (DILis) frequently don't show up even in stage three trials because it often happens too infrequently to show up until given to many thousands of people. An example of a similar phenomenon is that shortly after COVID vaccines came out, a few people had severe allergic reactions. As a result, the guidance almost immediately changed based upon these out of trial events to require that people getting their first COVID vaccine shot need to be observed for 15 minutes after receiving an njection.

Also, although I couldn't find a cite with for this fact with a minute of internet research, I read earlier today that nearly all drugs have been linked to liver injury on at least one occasion. As a result, a medicine that has a tiny chance of causing liver injury may have a confirmed case of liver injury.

With tirepatide, there are a few instances of likely liver injury caused by the drug. 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]; Fontana, et al. (2024). First Report of Tirzepatide Hepatotoxicity with Jaundice. Clin. Gastroentereology Hepatology, 22(12), 2538 [64-year old male; six weeks to onset; attached];
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; appears to the same incident reported in Berihun, et al., supra.

Does the fact that tirzepatide has been confirmed as a likely cause of heptatic injury on a few occasions mean that tirzepatide is more hepatoxic than reta, which has no such confirmed cases? The answer is no. The confirmed case of hepatoxicity with tirzepatide came after tirzepatide had been FDA approved and was in much wider use than in clinical trials. For more information on the risk of liver injury with tirzepatide, see LiverTox on Tirzepatide (C).

What should you do if you're worried about a liver injury with retatrutide? Getting a comprehensive metabolic panel every now and then wouldn't hurt because elevated liver enzymes or bilirubin could be a sign of liver injury. However, reta sometimes causes transient increases in liver enzymes not exceeding three times the upper limit of normal. Those are considered okay.

That's my two cents. I have no background in the natural sciences or medicine.

 

[rsmith]

I didn't follow your good advice. Instead I stopped reta again.

After reading some of the case reports from LiverTox after I spoke to you and had again stopped reta, I realized that there is a weirdness and almost randomness to how liver enzyme values change. To know whether the changes are significant enough to show that something is or is not a likely or probable cause of liver injury, I need to use the RUCAM calculator, the tool most often employed by researchers in determining whether something has caused a drug induced liver injury.

The reason I didn't follow your advice and keep taking the retatrutide is that I was worried about my liver. If I had a doctor advising me who would say that it would be fine to keep taking reta, I would have done so. But my hepatologist is not such a person even though he previously (with less data that I showed you) concluded that reta is probably not the cause of the elevated enzymes. I plan on staying off the retatrutide and the Lipitor until my liver enzyme levels are completely within the normal zone. That might not ever happen since my liver enzymes have been at least somewhat elevated since 2011, when my record of liver enzyme tests begins. However, I suspect being off of both Lipitor and retatrutide, there is at least a 50% chance of obtaining normal liver enzymes. If the liver enzymes return completely to normal, I'll restart reta. I'd stay on it unless any liver enzymes rose to a level of three times the upper limit of normal or higher, or unless I experienced sustained elevated liver enzymes even if below three times the upper limit of normal. In this post, I used the term "liver enzymes" to mean actual liver enzymes or bilirubin, which is not a liver enzyme, I think.

The technical information I provided may convince some that I know what I'm talking about. I am an excellent researcher. However, my Achille's heel is that I know very little about the hard sciences. Without a background in what I write about, it's quite easy for me to make mistakes when writing about things about which I do not know.

I don't have a problem with the approach you're taking. It's best to stay safe if you can. That said, your approach won't shed light on what if any contribution Tirz is making to your elevated ALT. Specifically, Tirz X Reta interaction.

While I agree with the statement in one of your citations (see below). It doesn't address the TIrz X Reta interaction that I suspect.

The risk for clinically apparent liver injury with long-term tirzepatide use is unknown but is likely to be very rare.,

My advice. If you get your ALT levels back down, consider quitting TIRZ and trying Reta solo. Perhaps even consider doing this (i.e., resuming Reta) after you've have cleared your system of Tirz for the most part. In this way, you will get a clearer picture of what Reta does to your liver. You may gain a few pounds during this time and fear of that may be what's keeping you on Tirz. I wouldn't sweat that because you will find a way to get it back off one way or another, maybe even with solo Reta (that would be my bet if I were to make one).

Whatever you decide to do, keep up with the excellent record keeping. Persistent research will solve this eventually IMO. If you're willing to share, are or were you ever a heavy smoker or drinker because either of these would matter as far as what's affecting your liver.

 

[keangkong]

I don't have a problem with the approach you're taking. It's best to stay safe if you can. That said, your approach won't shed light on what if any contribution Tirz is making to your elevated ALT. Specifically, Tirz X Reta interaction.

While I agree with the statement in one of your citations (see below). It doesn't address the TIrz X Reta interaction that I suspect.

The risk for clinically apparent liver injury with long-term tirzepatide use is unknown but is likely to be very rare.,

My advice. If you get your ALT levels back down, consider quitting TIRZ and trying Reta solo. Perhaps even consider doing this (i.e., resuming Reta) after you've have cleared your system of Tirz for the most part. In this way, you will get a clearer picture of what Reta does to your liver. You may gain a few pounds during this time and fear of that may be what's keeping you on Tirz. I wouldn't sweat that because you will find a way to get it back off one way or another, maybe even with solo Reta (that would be my bet if I were to make one).

Whatever you decide to do, keep up with the excellent record keeping. Persistent research will solve this eventually IMO. If you're willing to share, are or were you ever a heavy smoker or drinker because either of these would matter as far as what's affecting your liver.

I neither smoke nor drink alcohol.