Can Ozempic, Zepbound or Mounjaro Truly Transform Rheumatoid and Psoriatic Arthritis?

Can Ozempic, Mounjaro, Zepbound and Wegovy calm inflammation — not just melt away weight? In this episode of Thriving with Arthritis, Dr. Diana Girnita, board-certified rheumatologist and PhD in immunology, sits down with Dr. Vishnuteja Devalla to unpack the fast-growing science of GLP-1 medications in rheumatoid arthritis and psoriatic arthritis.

They break down how GLP-1 drugs actually work, why the same receptor lives on your immune cells, and what the latest evidence really shows for autoimmune disease — separating real science from the headlines and hype.

In this episode:

• What GLP-1 medications are and how they work (Ozempic, Wegovy, Mounjaro, Zepbound explained)
• The key difference between semaglutide and tirzepatide — and why GIP matters for weight loss
• How GLP-1 receptors on macrophages, neutrophils, and T cells calm inflammation
• The surprising drop in TNF-alpha, IL-1, IL-6 — the exact targets of our biologics
• What the UCLA study and PASI data reveal for RA and psoriatic arthritis
• Why obesity fuels inflammation and drives worse treatment response
• Will GLP-1s ever replace methotrexate or biologics? (The honest answer)
• Microdosing GLP-1s for inflammation — lower cost, fewer side effects
• The compounded-medication warning every patient needs to hear
• How to safely reduce medication when you start feeling better
• Where GLP-1 therapy is heading in the next 5 years

⚠️ This podcast is for educational purposes only and is not medical advice. Always talk with your own rheumatologist before starting, stopping, or changing any medication.

Transcript

Dr. Girnita: Welcome back to the Thriving with Arthritis Show. I'm very glad to have you here to discuss GLP-1 medications, which are everywhere in the headlines right now. If you open Google or look in a magazine, I bet you'll see something about GLP-1 medications.

Dr. Devalla: Yes. It seems like every week there's a new indication for these medications, and the applications are just exploding. I think we're all struggling to keep up — on the clinician side and the patient side. This space is growing fast.

Dr. Girnita: True. For those who don't know what GLP-1s are, let's explain to our patients and listeners what these medications are and how they actually work.

Dr. Devalla: This is a great place to start. GLP-1 stands for glucagon-like peptide-1. It's a hormone our gut naturally releases after we eat. There's data suggesting that what you eat influences how much of this hormone your gut produces.

This hormone has several functions. After you eat, your gut produces it, and it stimulates your pancreas to release insulin, which helps us process glucose and nutrition. It also tells the brain that you've just eaten. I find this really interesting, because it's not the food itself that tells you you're full — it's the hormone signaling your brain that you've eaten and you're full.

The other mechanism is that it slows down your gut. After you eat, blood flow to your gut increases quite a bit to help absorb nutrition. To maximize that absorption, your gut slows down, so the food travels a little slower and gives you the chance to absorb as much nutrition, fat, and calories as possible.

Those are the main mechanisms. The medications that have come out basically mimic this hormone. What's interesting is that the natural GLP-1 your gut produces is broken down very quickly — so you feel hungry again and can eat again. The main difference between the natural hormone and the injection or tablet is that the medication is designed to last longer. It tricks your mind into thinking you're full for longer. That's the biggest difference: the medications simply last a lot longer than the natural hormone.

Dr. Girnita: True. There are many GLP-1 medications on the market now. We all know Ozempic, but over the last two years we've heard about Wegovy, Mounjaro, Zepbound, and more. What's the real difference between these drugs?

Dr. Devalla: There are quite a few, and I expect we'll have even more in the coming years, because pharmaceutical companies are investing heavily given all the benefits. Essentially, they all mimic the same hormone.

Wegovy's active ingredient is semaglutide. Mounjaro, made by Eli Lilly, has the active ingredient tirzepatide. They're very similar, and they have several names because they're marketed either for patients with diabetes or for weight loss — but they're essentially the same medication.

The key difference is that tirzepatide also inhibits an additional hormone, GIP — gastric inhibitory polypeptide. Mimicking that hormone along with GLP-1 produces additional weight loss, because GIP plays a key role in fat metabolism. In studies, Wegovy gets you to about 15% weight loss on average, and Zepbound gets you to about 20%.

What I tell my patients is that the percentages don't matter so much, because how a patient tolerates and responds to the medication varies greatly. You might tolerate Zepbound but it may not work for you; you might not tolerate Ozempic but it works fantastically. There's a lot of variability in how we respond. Studies suggest one thing, but in reality it's about what best suits you and what you tolerate. And insurance plays a big role in what you get to take. So there are a lot of different GLP-1s with different names, but in theory they all do relatively the same thing.

Dr. Girnita: So someone who doesn't respond to Ozempic can actually try another medication. Is that correct?

Dr. Devalla: Yes. If you don't tolerate one GLP-1, that doesn't mean you won't tolerate any of them. They all vary slightly, and one may work wonders for you. We've seen this in practice — patients go on Wegovy, can't tolerate it, switch to Zepbound and do really well, and vice versa. It's important for patients to know it's worth trying several different options if that's what they're interested in.

Dr. Girnita: One of the effects generating a lot of interest is that GLP-1s might actually calm down inflammation. This is the part I'd like to dive into, because it's very connected to our patients suffering from autoimmune diseases and inflammatory arthritis. In your opinion, how do GLP-1s calm inflammation, and what immune cells are involved in this process?

Dr. Devalla: GLP-1's role in inflammation is so important for us — this is something we deal with every day. What's really interesting is that the GLP-1 receptor exists outside of the gut, on immune cells. Who knew that a hormone that helps with food and digestion plays a role in the immune system?

Research has shown that many immune cells express this receptor, and activating it changes the cells. In rheumatoid arthritis or psoriatic arthritis, a lot of the active immune cells are macrophages and neutrophils — cells that maintain the health of our immune system and help defend us from bugs and viruses. They're very pro-inflammatory, because inflammation is also good for us; it helps us fight disease.

They've identified GLP-1 receptors on macrophages, neutrophils, monocytes, and even T cells — all of which play a role in our immune system. What's even more interesting is that activating this receptor actually calmed these cells down.

Dr. Girnita: That's another connection between the immune system and the gut. We've talked before about how the immune system talks with the bacteria in the gut. This is another piece of evidence that the immune system is still so poorly understood — and again, it's connected with a hormone related to digestion in the gut.

Dr. Devalla: Even after spending decades understanding the science of our body, I can't believe it continues to surprise us constantly. I'm often amazed by how connected our systems are. That's why I find it fascinating that a gut hormone plays such a big role in the immune system.

The studies showed that activating this receptor calms the macrophages and neutrophils — and not only that, they saw a net reduction in inflammatory proteins downstream. So it's not just calming the cells; there's a real reduction. What's amazing is that in the study looking at inflammatory proteins, the greatest reductions were in TNF-alpha, IL-1, IL-6, and IL-10 — all of our targets for biologics. When I saw that, I was just amazed.

Dr. Girnita: And it's also an explanation for what's happening to patients who use the drug, lose weight — and some who didn't even lose weight, but we'll talk about that — and start to see their other drugs working better. Since you mentioned inflammatory arthritis, let's dive into the science we have for rheumatoid arthritis. What does the evidence actually say about GLP-1 medications in patients with rheumatoid arthritis?

Dr. Devalla: Overall, the evidence is positive. There are a lot of ongoing studies, especially randomized controlled trials. We don't have any randomized controlled trials yet, but the biggest study so far is from UCLA. They looked retrospectively at patients with rheumatoid arthritis who had a BMI greater than 27 and went on a GLP-1 analog — semaglutide or tirzepatide — and they saw a significant reduction in disease activity. Up to 35% of those patients saw a reduction in disease activity, compared to only about 17% of the patients who did not take a GLP-1. So there's a meaningful difference.

Now, we can't yet say whether that's directly due to weight loss or to anti-inflammatory effects — my guess would be both. Ongoing studies will help us tease that out. Honestly, I don't think it matters much. The point is it's helping. You're better with standard of care plus a GLP-1 than with standard of care alone, when the GLP-1 is indicated. It's great to know we have another team player we can use to help patients feel better.

Dr. Girnita: How about patients with psoriasis or psoriatic arthritis? What do we know about them?

Dr. Devalla: In our world, we're primarily dealing with the arthritis component, but psoriasis is very much part of our decision-making. Whenever my psoriatic arthritis patients come in and their joint pain isn't under control, one of the questions we ask is, "How's your psoriasis?" — because we always have to choose a medication that checks both boxes.

The evidence for GLP-1 use in psoriasis and psoriatic arthritis is way more robust than in rheumatoid arthritis. The score we use to track psoriasis activity is the PASI — the Psoriasis Area and Severity Index. In studies unrelated to biologics, they looked at patients with psoriasis on GLP-1s alone and saw a 50% reduction in the PASI score, which is incredible. That is medicine on its own for psoriasis.

Subsequent studies also showed significant improvement in disease activity in patients with psoriatic arthritis. We've known for a long time that weight loss helps with psoriasis and psoriatic arthritis, so weight tends to play a bigger role in the inflammation related to these conditions — but now we're starting to see the relationship even more clearly.

Dr. Girnita: It's important for people to know that obesity is directly linked to more inflammation. Adipose tissue is not an inert tissue — it produces molecules that create more inflammation. From my research on rheumatoid arthritis, people with obesity have an increased risk of developing RA, and they have a higher risk of responding less to anti-inflammatory medication. I've seen this in my patients.

I often tell the story of one of my patients with psoriasis and psoriatic arthritis who struggled for many years. I switched four or five medications, then put him on an infusion, hoping to dose it based on his weight. Even then, the results were good but not impressive. Then I had a real conversation with him — because losing weight is hard, and maintaining it is even harder, since our brain resets the need to eat more to get back to the previous weight.

This patient agreed to start a GLP-1, and in about six months the medication worked like wonders. His psoriasis was almost gone. Within a year, I was decreasing medication instead of escalating it — and this was years before everyone was hyped about GLP-1s. That's when I understood that the metabolic piece of controlling inflammation is just as important as our targets — the TNF-alpha, IL-6, the JAK pathway.

In rheumatology, we don't usually talk about metabolism or the metabolic piece of inflammation. We just use a very targeted biologic to dampen the inflammatory pathway. But patients are a whole — they're not just an inflammatory pathway versus a metabolic pathway. We tend to close our eyes and not address it. So let me ask you: will GLP-1s replace medications like methotrexate, or replace a biologic?

Dr. Devalla: That answer is pretty simple — a resounding no. Our medications — methotrexate, DMARDs, biologics — have been around and very well studied. They save lives, they've proven themselves over and over, and they help our patients live better, longer, healthier lives. I don't think they'll ever replace the standard of care.

But I always get excited when we can do more, offer more, and cover more ground. That's where GLP-1s play a role: you take advantage of the standard of care we always stand behind, and here's an option that may get you even further and help you make more progress in other areas of your life too. Obesity is a big problem in this country, and we're finally starting to see that it's not just weight — it plays a huge role in your immune system, and even in depression. We're a whole person, and that's very much our philosophy at Rheumatologist OnCall: we treat the whole person, not just a disease. We get excited whenever there are options we can add to the standard of care, because it brings the person closer to a healthier life.

Dr. Girnita: We need to tell people that we believe in science, and we apply science before we apply the hype. We're all for integrating options to get people better and into remission faster and keep them there — but we never take things lightly. So let's talk about what patients should do if they start feeling better. Should they stop their medication on their own? Modify it on their own? What would you recommend?

Dr. Devalla: I would not recommend that patients make medication decisions on their own. Inflammation can be silent — just because you're not in pain doesn't mean you're free of inflammation, because it can do damage without letting you know. In patients with rheumatoid arthritis and psoriatic arthritis, the heart disease risk is three to four times higher than average, and you can't feel that inflammation working against you. You can feel it in your joints, but not in your heart or vessels. So it's really important to discuss medication changes with your rheumatologist.

We are always supportive. If patients feel great and want to try reducing medications, we can do that safely — we do it all the time. I've seen many patients who went through dramatic weight loss come off significant amounts of medication, just like the patient you mentioned. If patients feel better, that's a great start and the right time to have a conversation about a strategy to reduce medications. I'm all for less medication — if you can get the same benefits with less, I'm for it, and I think most rheumatologists are too. But don't make major changes on your own.

Dr. Girnita: Let me ask you: how many rheumatologists in this country do you think are discussing GLP-1 medications with their patients?

Dr. Devalla: Probably not many. A lot of rheumatologists don't have the opportunity to discuss alternatives to standard of care because of time constraints and the way the system is set up. But this is where we stand apart — we see the patient as a whole. It's not just the disease we're treating; the best outcome is making the whole patient better, not just the disease.

Dr. Girnita: In 2024, I was probably the first rheumatologist to publicly talk about the possibility of using GLP-1s alongside standard therapy — not to replace it, just to complement our standard of care. I published a video on this, and followed it with another more recently discussing the evidence. A lot of patients leave me comments that their rheumatologists don't want to address the topic or don't believe in the opportunity.

Last year we went to the American College of Rheumatology meeting and attended presentations on GLP-1s in rheumatoid and psoriatic arthritis. I was so happy to see that mindset finally being challenged and people starting to adopt it — though it will probably take another two or three years before more rheumatologists start talking to their patients about adding GLP-1s to standard therapy to get to a better disease activity state.

Since we're talking about GLP-1s, there's a lot of discussion about microdosing — especially for patients who don't necessarily need to lose weight, or a lot of weight. Can you explain what microdosing is, and what you believe about it? Could it help patients with inflammation?

Dr. Devalla: At this point, I think microdosing can be helpful. Instead of the standard weight-loss doses, the studies have used 10 to 15% of that — we call that a microdose. What the studies are trying to highlight is whether the positive impact of GLP-1s is purely related to weight or to something else.

Patients can still lose weight with a microdose, but it's not as dramatic. Research has shown that microdosing may be enough to get the anti-inflammatory effects without a major change in weight. Those studies are ongoing.

There are real benefits to microdosing. The biggest is cost — these medications are expensive, and if you're paying out of pocket, using 10 to 15% of the medication versus the full dose costs less and lasts a lot longer. The other benefit is a lower side-effect profile; patients tolerate microdoses much better than the standard dose. If you can improve tolerability, improve cost, and get the same anti-inflammatory effects, that's a great place to begin. Overall, I'd say microdosing seems to be helpful, and I think we'll get more robust data moving forward.

I want to go back to your earlier point about sticking with the science and seeing patterns. You talked about this in 2024, and I think that's what sets us apart from the herd — we're always trying to find additional options to help our patients feel better. Why aren't other rheumatologists talking about it? I think there's a lot to deal with in our clinics, with pressures coming from all directions. But this is where we stand apart — thinking about the whole person and offering additional treatment modes alongside the standard of care in the hope of getting you further.

Dr. Girnita: True. We are not a wellness clinic. We offer comfort for the patient, but we don't sell dreams. We stick to the science and want to use things that are safer for our patients and have scientific value.

Dr. Devalla: Going back to microdosing — I think it's overall positive, and I recommend it to patients, especially if they have an elevated BMI that would benefit from it anyway, outside of the autoimmune disease. Within the coming years we'll get much more robust data to support this.

Dr. Girnita: I've used a microdose of a GLP-1 for some patients, and it not only helped tremendously — especially with pain and fatigue — but I was also able to decrease some of their medications. These were patients who had tried other biologics, and combinations of biologics and DMARDs. I'm not saying it works for everybody, but in some patients it seems to make a difference.

In my opinion, that's related to the GLP-1 acting on different types of cells that carry these receptors. Instead of just a targeted medication — say a TNF-alpha inhibitor that only targets TNF-alpha — adding a GLP-1 probably targets multiple cells producing not only TNF-alpha but also IL-1 and IL-6. In my opinion, that was the key to the response. I don't have all the data to prove it, but this is a reality I've seen in some patients.

Now, you mentioned insurance companies and cost. We don't expect these medications will be approved for inflammation in the next five years — correct? Or do you expect that?

Dr. Devalla: We already have trouble with biologics, so I doubt we'll see that kind of approval for inflammation — unless the data that comes out is really robust and shows it makes a tremendous difference in our patients' lives.

Dr. Girnita: We also have problems getting these medications approved for people with obesity. If, as a rheumatologist, you try to approve a GLP-1 for a patient with obesity, they'll deny you and ask you to try diets and other medications first. Most of our patients don't have five years to wait until this drug is approved. So what are the real options for patients willing to pay for a medication like this? How can they find a safe solution?

Dr. Devalla: One word of caution: I would stay away from compounded medications. Even though they're cheaper, the filling agents vary greatly and none of them are FDA-approved. Patients have been reacting really poorly to some of these compounding agents, and we don't know where they come from or how they're made.

If you're willing to pay, the best option is to buy directly from the company — Eli Lilly or Novo Nordisk. Many of these companies now offer direct-to-consumer options. It comes from a safe place, carries all the FDA labels, and all you need is a prescription from your rheumatologist or physician. So the best option is to buy directly from the company and stay away from compounded medications.

Dr. Girnita: That's important to say, because a lot of patients buy from compounding pharmacies to save money. I'm not saying all compounding pharmacies fail to follow protocols — but the variability is so huge that we really don't know what's in the vial. Many will write "for research purposes only" on the vial, and with that they take their hands off the liability. A patient could end up with a lot of side effects, or no effect at all — because that's the other risk. You buy something that isn't cheap, put something with essentially no regulation into your body, and then you're disappointed because there may be nothing in those vials that works.

We've talked a lot about this medication, and I'm really happy we're discussing the science and not the hype. Because the science is evolving, and we hear about a new indication almost every month — where do you think we'll be five years from now? Are we all going to be taking a GLP-1?

Dr. Devalla: I don't know about all of us taking GLP-1s, but I think they'll play a bigger role in medicine as a whole, and a bigger role outside of obesity. They've already transformed how we treat and approach obesity, and fixing that alone makes a huge improvement in patients' lives.

For our patients with inflammatory conditions who are overweight or obese, the world I envision is using GLP-1s concomitantly with the standard of care, addressing multiple issues at the same time. That patient would get to remission much quicker, and potentially we could get away with less medication too.

In five years, I think our overall use of GLP-1s will increase, and we won't be as afraid of having that conversation with our patients — especially those who are overweight or obese. In the long term, I think these medications will pay for themselves, especially given the reduction in heart disease and in flares of rheumatoid and psoriatic arthritis. But the insurance companies have to see it that way too.

Dr. Girnita: Absolutely. Dr. Devalla, thank you very much for this insightful discussion about GLP-1s and our types of arthritis — rheumatoid and psoriatic. I hope that in the next couple of years, more rheumatologists will have these conversations with their patients, and that we open the floor for others to consider these medications and incorporate them into their practice to help patients. Like you, I'm a believer in adding medication to optimize the care of our patients.

With that, I'd like to thank everyone for listening to our podcast, and I invite you to the next one.

Dr. Devalla: Thank you.