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Switching from one GLP-1 RA to another?
I started on zepbound (tirzepatide) in a quest to reduce the pain of my knee arthritis -- buy time before replacing the joint -- which worked, but triggered a number of side effects that eventually became intolerable. Switched to ozempic (semaglutide). On the plus side, this really did reduce the side effects. (It helped that it's a multipen, which means I could click-dose.) On the minus side, apparently arthritis is emerging as a semaglutide side effect, and it may be one of mine. Everything else is going well, but the arthritis symptoms are coming back. So I'm thinking about switching again, if my orthopedist confirms that this is what's going on. I can go back to tirzepatide, or consider one of the older GLP-1RAs, like exanatide XR or dulaglutide. Or I could wait it out, and switch to a new product now in the pipeline when it becomes commercially available. Or I could get really creative, and alternate 6 months on semaglutide and 6 months on tirzepatide. Or something. Anyone else have experience with switching between these meds or thoughts on how to approach this problem?
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@projfan, did you switch? How is it going?
I switched from tirzepatide to semaglutide, and overall, it's much better. I've got an orthopedist appointment coming up in March, because I now think the knee pain is not actually the arthritis coming back and has nothing to do with the GLA-1 RA -- I suspect it's a fragment of bone snapped off and caught under the kneecap. I love the ozempic multipen, which has allowed me to click-count (https://pmc.ncbi.nlm.nih.gov/articles/PMC3262738/) and fine-tune the dosage -- that alone is worth the price of admission, as it were. Currently working on the remaining side effects one at a time: eliminated simvastatin, which helped the GLP-1 RA orthostatic hypotension quite a bit, and have been able to drop one of my migraine prevention meds by managing my nocturnal hypoglycemia. Next up are constipation and sleep. Hoping to be stable by the summer.
I'm sorry to hear about your challenges with both tirzepatide and semaglutide. Managing arthritis pain while dealing with medication side effects is definitely frustrating.
Based on your experience, it sounds like you're caught in a difficult situation where tirzepatide helped your arthritis but had intolerable side effects, while semaglutide reduced those side effects but may be worsening your arthritis symptoms.
I haven't personally switched between these medications, but a few thoughts on your options:
The alternating 6-month approach is creative and might allow you to get some benefits from both while minimizing cumulative side effects. However, this would be somewhat experimental, and you'd want to discuss with your doctor if constantly switching might create other issues.
If your orthopedist confirms semaglutide is affecting your arthritis, returning to tirzepatide at a lower dose might be worth considering. Sometimes side effects are dose-dependent, and a reduced dose might still provide some arthritis benefit with fewer side effects.
Regarding the older GLP-1RAs like exenatide XR or dulaglutide, they might have different side effect profiles that work better for your specific situation. Each of these medications, despite being in the same class, can affect individuals differently.
Have you discussed with your doctor the possibility of combining a lower dose of one of these medications with other arthritis management approaches (physical therapy, topical treatments, etc.)?
Whatever you decide, I'd recommend keeping a detailed symptom journal to help track how each medication affects both your arthritis and any side effects. This data would be valuable for both you and your healthcare team.
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1 ReactionYou and I are largely on the same page. Let's see...
I took tirzepatide to the lowest commercially available dose before switching to semaglutide. Some side effects proved dose-dependent, but most did not. I would have played with it longer if I could click-dose, but of course, you can't do that with the weight-loss drug versions in this country, I'm not prepared to buy out of the country, and my doctor has had poor experiences with the vials.
Other than the arthritis, my experience with semaglutide has been better. I've got an ortho appointment in March. I've tried a metric ton of arthritis solutions before I got to this point, but plan to ask about one I haven't tried: botox. It's also possible that it was coincidence rather than causation: I'm now thinking I might, once again, have had a tiny bit of bone break off in the joint and get caught under the kneecap. Had that once before, and it won't kill you, but it isn't fun. There's a grinding happening in that knee that isn't in the other, so perhaps.
I'm actually kind of curious about the old GLP-1 RAs, but at this point, my priorities are to (a) work down the side effects, manage my various decaying parts, and getting my incipient polypharmacy under control by rebuilding my entire drug suite (I'm about 1/3 there), (b) stabilize the situation, (c) get a second opinion on the TKA so I know where I stand, and (d) regroup after everything has been stable for several months. I'm also working through the process of getting a decent diagnosis on peripheral neuropathy, which started while I was still on the ramp-up phase of tirzepatide. It seems to have been triggered by excess B6 (who knew?), but there's something else underlying it, since dumping the B6 hasn't fixed the PN, although it has slowed down the progression. It's not the obvious candidates, because those tests have been negative or inconclusive. The most recent test suggests maybe MGUS? We'll see.
It's a dance, since all the pieces tend to interact. I'll get there eventually. And the insights I've gained on Mayo boards from others have been helpful all around -- thank you!