Switching from one GLP-1 RA to another?

@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.

You 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!

I have been on Oz for 2 years (for weigh loss and type 2). I did lose 35 lbs in the beginning. I guess I felt fuller? Not sure but it did seem to come off. I am currently struggling. Need to lose 35+ lbs. I feel like I'm always hungry. I asked my doctor if I could try and switch to Mounjaro. She said ok but i'm not sure she knows much about switching so I am seeking advice from others. Has anyone had success switching from one to another? also I am on 2.o of Oz. What amount of Mounjaro would I go on?

Thank you all for your advice!

@melissa123 - I did this weight loss medication change you mentioned because although I lost about 54 pounds on semaglutide (Wegovy - Ozempic for use in those who are diabetic) I had really harsh GI symptoms from the shots and was having trouble continuing. So, my doctor had me go off of semaglutide for a month to determine if my symptoms were indeed linked to the semaglutide or something other. They were, we learned.

I gained weight at an alarming rate while off the semaglutide, which my doctor confirmed was normal when I shared the figures with her.

She then started me on tirzepatide
(Zepbound, and Mounjaro for those with diabetes). I had to start at the very first dose and titrate up. I'm having very few side effects, but I'm also not feeling this med is holding me back from eating like the semaglutide by itself did.

My weight loss has been frustratingly low on my new med, like a pound. My doctor tells me to have patience.

Hoping this all works out favorably in the end.

Wow, how long were you off Wegovy for before you started back up on your new med? I would be switching right away. Also did you gain weight because you ate more? I hear people gain weight quickly if they go off the meds.

It was about 5 weeks, between the 4 weeks my doctor wanted me to trial off the semaglutide to isolate better what the cause of the severe GI side effects were and then the insurance approval for the different medicine. I did naturally eat more cause I was no longer on the appetite-suppressing medicine. My doctor advised me this would happen and that I might feel really hungry when trialling off.

I did this in the other direction. (I do not have diabetes -- just losing some weight I had gained back after bariatric surgery 15 years ago.) I lost weight on tirzepatide, struggled with the side effects, and shifted to semaglutide for maintenance. I have a history of weight cycling (which means I've gained and lost and gained and lost weight over much of my life), so I knew when I got on this ride, I would need to stay on it for life.

I would say that switching is a great choice, because people who have problems with one formulation don't necessarily have the same problems with the other. Also, not surprisingly, there is not a lot of research on this topic, because really, who would pay for it? This is a bit old, but the most helpful paper I found: https://pmc.ncbi.nlm.nih.gov/articles/PMC7900946/.

Yes, titration is critical if you are prone to side effects, and weight loss is unlikely at the initial low dose. I titrated up on the tirzepatide even more slowly than recommended, and held below the max dose until I lost most of my goal weight, because my side effects were pretty awful. Nonetheless, the tirzepatide got me there. I then titrated down before switching to semaglutide, and titrated back up a little bit for a maintenance dose.

Yes, it's really common for the weight to come back on when you stop, because the drugs do nothing structural, don't retrain us, and leave the body relatively fast. There are pretty deep arguments going on in the field between the on-it-for-life-this-is-equivalent-to-a-statin camp, and the make-lifestyle-modifications-and-then-stop-the-drug-and-it-will-all-be-fine camp. The problem is that insurance doesn't want to pay for the drug for life, and they also don't want to pay to support all the work needed for the lifestyle changes. It's a disease, and willpower doesn't work to conquer a disease, so the lifestyle changes are not trivial. As you can tell, I'm in the first camp. (As a result, I continue to keep an eye out for new formulations and options.)

Unfortunately, you can't click-count or microdose with the single-dose pens that Mounjaro and Zepbound use, which could otherwise be helpful in managing side effects and price.

Also unfortunately, the maintenance dose that is now managing most of my side effects pretty effectively, also brought back the "food noise". So far, I've been managing through that problem.

If you have not considered it, you might talk with your doctor about bariatric surgery. Surgery always comes with risk, of course, but I found it amazing and only wish I had been ready to consider it when I was younger. The weight regain was very slow and honestly, in part my own fault for not maintaining the behavioral changes. Unlike the drugs, where they just throw you in the deep end and walk away, the surgery should come along with comprehensive support for behavioral/lifestyle changes. And there is something to be said for one-and-done. I have no idea if insurance would require you to demonstrate weight gain after coming off the drugs before they would approve the surgery -- mine happened before the drugs were an option.

I switched from OZ 2.0 to Monjaro a few months back. Started at 5 mg for 2 months, then 10 mg for same and am now moving to 12.5 mg. Good news was @ 10 of Monjaro, my A1C went from 6.8 to 6.2 without me making any changes. No weight loss over same period. I had RNY bypass 38 years ago. No problem with switching meds. My issue was on day six, Monjaro half life was over and I felt hungrier. It took another day after new injection for it to work again. I wish Monjaro had a screw top as the large gray plug is hard to refrigerate and carry enough when traveling for a few weeks. Best of luck to you.