Case Study - GLP-1 Agonists and Medication Absorption - Part 2

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In part 1 we talked about the research (or lack thereof) around the ways in which GLP-1 drugs, taken in large doses for weight loss, might impact the absorption of other medications. Today, we’re going to hear from someone who was personally impacted by the issue. I received the following information from Jennifer Jonsson who gave me permission to publish it and use her name.  

Jennifer initially sent me this email:

I have Type 2 diabetes and my regular doc put me on Rybelsus [editor’s note: this is a pill form of Semaglutide, taken daily,] which is one of the semaglutide drugs that people are using to lose weight as well as for diabetes. I also have ADHD and bipolar disorder. Within about 4 weeks of taking Rybelsus, I was scatterbrained, anxious, angry, manic and close to losing my job for the way I was behaving.  Turns out, semaglutide interferes with absorption of other medications quite a bit, especially time-released meds, and NOBODY KNOWS ABOUT THIS.  My Regular Doc didn't know.  My psychiatrist didn't know. 

My psychiatrist tried to find some workarounds and they were both unpleasant and only partially successful.  I'm off Rybelsus now and starting to feel better but I think about the various incredibly bad possible outcomes and I just get chills.  Personally, the last time I was manic, I thought it would be a really great idea to drive to another town and open a Chinese restaurant.  (I can't cook, don't own any property and don't have any money, but sure, a restaurant.  Why not.)  So my wife is hiding the car keys.  Anyway, I'm going to be okay but PEOPLE NEED TO KNOW ABOUT THIS.  

When I inquired about publishing her experience, she sent a follow-up to provide more details:

When I was first diagnosed with T2 diabetes in November 2023, my Regular Doc wanted to put me on Ozempic right away.  I said no and asked for Metformin. Metformin used to be the drug they tried first and I can't remember when that changed.  I couldn't tolerate a high enough dose of Metformin to be effective in controlling blood sugar, so we added 3mg of Rybelsus.  The problems began after I went up to 7 mg of Rybelsus, as one does, so about 4 weeks in.  

When I became aware of the problems (I'm not the best self monitor), my psychiatrist suggested I wake up an hour early, pry the psych meds out of their capsules, put the powder in a glass of water, then drink the glass of water, then go back to sleep.  This got the drugs into my system when Rybelsus was at its weakest, because one takes Rybelsus first thing in the morning before breakfast. Also, taking the meds out of their time release capsules meant that I'd absorb more of them.  At the time, this seemed like a reasonable workaround. However, taking a strong time-release stimulant in a glass of water in the middle of the night obviously caused serious sleep problems.  I did get some benefit, but I also started crashing and burning around 2 in the afternoon (not surprising, since I was taking the medication 3 hours early and not getting enough sleep).  Also, the powder didn't taste great.  Minor consideration, but in terms of compliance, maybe huge. I also note that this workaround would not have worked at all with Ozempic or the other time-release injectables, which don't have a "weak" time of day.  

I saw my psychiatrist last Tuesday and he said if it were him, he would stop the Rybelsus.  I talked to my wife and some friends, too, and they all basically said, "If the Rybelsus is causing the problem, stop the Rybelsus."  Which I did. When I saw my Regular Doc to get a different drug prescribed, I took my wife with me because I thought I'd get pushback without her there and I think I was right.  After I explained that the semaglutide was wreaking havoc, she kind of sighed and said, "Well, at least we tried." (We who? This wasn't my idea.) Anyway, I'm now taking Januvia, which seems to be mostly harmless, and 500mg Metformin  Since it takes semaglutide 5 to 6 weeks (!) to leave a person's system, things are getting gradually better but not very fast. My psychiatrist gave me a second drug to take in the afternoon to help with the 2pm crash and burn, which has helped some.  

This whole mess negatively affected just about every aspect of my life, especially my job.  I worked half-time at home for a week and took at least three full days off because I just couldn't get it together and get to the office. (Management has been great about it and has not pushed me for details.)  I handle a lot of logistical information for my company that we really depend on to make pretty major decisions and I was starting to think I was no longer competent to do it and should maybe quit, or go on extended medical leave. I was also afraid I'd screw up something major and get fired. I was also snappish, cranky and hard to be around.  My wife has lived with me for 25 years at this point and is used to this happening from time to time, but a lot of people would not have been as patient.  I mean, yes, I did lose 7 pounds while all this was going on, but I don't think that's worth the loss of my job, my marriage and all of my friends.  

I want to thank Jennifer for allowing me to share her story. If you want to hear more from her, she blogs at https://bigbadbuddhist.blogspot.com

UPDATE: I received the following, which I have permission to share anonymously:

I’m a community health nurse who works with folks with serious persistent mental illness. Your post about GLP-1 agonists and medication absorption was incredibly helpful, and thank you to Jennifer Jonsson for allowing you to share her experience. Because of that post, I was able to caution one of my patients who had recently started Rybelsus about it possibly impacting the efficacy of her anti-psychotics. Sure enough, 9-10 days after she titrated up to 7 mg (her maintenance dose), she began having suicidal ideation. Thankfully, she had the wherewithal to stop the medication and is feeling much better. I was also able to share your post with everyone in our agency so that they can be prepared to look for increased psychosis should their patients start one of these meds. Thank you for the work you do and for spreading the word. You are quite literally saving people’s lives.

Of course, this is just two people’s experience and your experience may be different, but if you take other meds (especially the kind we discussed in Part 1) this is something to be aware of and to speak with your healthcare provider(s) and/or pharmacist(s) about.

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More research and resources:
https://haeshealthsheets.com/resources/

*Note on language: I use “fat” as a neutral descriptor as used by the fat activist community, I use “ob*se” and “overw*ight” to acknowledge that these are terms that were created to medicalize and pathologize fat bodies, with roots in racism and specifically anti-Blackness. Please read Sabrina Strings’ Fearing the Black Body – the Racial Origins of Fat Phobia and Da’Shaun Harrison’s Belly of the Beast: The Politics of Anti-Fatness as Anti-Blackness for more on this.