IBD Drive Time: Colleen Kelly, MD, on Obesity and IBD

Host Raymond Cross, MD, calls on Dr Colleen Kelly to discuss the increasing prevalence of obesity among patients with IBD, how obesity can complicate Crohn's disease and ulcerative colitis, and the role of GLP-1 RAs and bariatric surgery in treating patients.

Raymond Cross, MD, is director of the IBD Center at Mercy Medical Center in Baltimore, Maryland, and professor of medicine at the University of Maryland. Colleen Kelly, MD, is a gastroenterologist specializing in the treatment of IBD at Mass General-Brigham in Boston, Massachusetts.

Obesity and Inflammatory Bowel Disease (IBD): Prevalence, Outcomes, and Emerging Therapeutic Considerations

• IBD + obesity prevalence and drivers: Between 15–40% of adults with IBD in the US have obesity and ~20–40% are overweight, paralleling ~70% overweight/obesity in US adults. Contributors include corticosteroid exposure, diet changes (more refined starches, less fiber), sedentary behavior, and potential weight gain signals with JAK inhibitors (e.g., tofacitinib, upadacitinib). Anti-TNF therapies have not shown consistent sex-based weight differences in trials.
• Obesity impact on IBD outcomes and biologic response: Higher BMI is associated with worse disease activity, more relapses/flares, and increased complications. In ulcerative colitis, obesity during hospitalization increases surgery risk and length of stay; post-IPAA outcomes are worse. In Crohn’s disease, visceral/central obesity correlates with penetrating/stricturing disease and more hospitalizations. Pharmacokinetics are affected, contributing to earlier loss of biologic response.
• Management considerations (medical and surgical): GLP-1 receptor agonists produce effective weight loss but about 10% of patients do not respond to this therapy. Weight regain of up to two-thirds occurs within 1 year after discontinuation, supporting long-term use. GI adverse effects may confound IBD symptoms. Bariatric surgery favors sleeve gastrectomy over Roux-en-Y due to fewer complications; careful selection and disease control are essential. Preoperative weight loss may improve surgical outcomes for patients receiving a J-pouch or stoma.

Dr Cross: 

Welcome everyone to IBD Drive Time, which is the official podcast of the AIBD Network. I'm delighted to have my friend Colleen Kelly from Mass General Brigham Health System. I'm here today to talk about obesity and IBD, and I understand that this is Colleen's first podcast she's ever done. So welcome to IBD Drive Time.

Dr Kelly:

Thank you. Thank you for inviting me.

Dr Cross:

So we were together at the research committee meeting in Las Vegas, and we had a nice lunch talking about obesity and IBD and potential the future directions of how that's going to be managed. So I thought this would be a timely topic for IBD Drive Time. So first off, when I talk to people that aren't in medicine about IBD, there's an impression that patients with Crohn's and colitis are incredibly thin and cachectic, and that's clearly not true. So is obesity more or less prevalent in our patients with IBD?

Dr Kelly:

Definitely more. And it really mirrors the problem that we're seeing in the general population where about 70% of US adults are overweight or obese, very similar numbers. There's some range, but really it's like 15 to 40% of adult patients with IBD have obesity, and another 20 to 40% are overweight. There's a lot, I guess, contributing to that. There's all of the factors that is keeping the problem going for everybody, but there are factors very specific to IBD. We use obesogenic medications like corticosteroids. There's some patients are eating differently to avoid symptoms, maybe more refined starches, less fiber. They may be more sedentary because of fatigue and joint pains.

And then there's even some of the biologics we use. I don't know if you've seen this, but I've had patients lately telling me that they're gaining weight on Rinvoq and tofa and asking around other people are sort of observing this. And I looked a little bit into it and there's some rheum studies anyway on tofacitinib where there's some weight gain and it has to do with the potential for the drug to block leptin, which is a satiety hormone that feeds back on the brain. So there's a lot of factors that our patients have.

Dr Cross:

So I was going to make two comments. So one, it's interesting that you and I grew up when all we had were anti-TNF therapies to use for our patients with IBD. And it was more common in women than men, but after you got their disease under control, a common complaint was, "I'm gaining weight and I think it's my anti-TNF." And I used to poo-poo them and say, "No, that's because you're no longer a hamster on the wheel. We've controlled inflammation. Now you're like the rest of us, you have to exercise, push away from the table."

And I saw this very interesting piece on 60 Minutes that was talking about men and women in clinical trials and how they only use mice and rats that are males for studies because they don't want to deal with quote “women hormones.” And they were talking about Ambien and how women do not process Ambien as well as men. And so women were taking Ambien doses that men were using and they were having car accidents and other things were happening. And long story short, we tried to address this by looking at the pivotal trials with anti-TNF therapies and trying to adjust for confounding. And it looked like really that men and women, there really wasn't any differential changes in weight gain. And that was at the time when we thought all these pharmacokinetic factors would influence how people process anti-TNF. So long story short, I don't think for anti-TNFs it makes a difference, but maybe with JAKs it does. Would that change who you offer a JAK to based on what you're learning?

Dr Kelly:

I don't think so. I think this needs to really be looked at a little more in detail in IBD patients, and it's something to watch out for. Any of your IBD patients as they're gaining weight, and if you think it could be a result of a medication that they're on, you see it sometimes in ... I mean, we see patients who are on certain antidepressants or antipsychotics can gain weight from those and they'll use metformin to mitigate that. So just I think being aware of it and listening to them, because this can really be disturbing, especially to young women patients and they're seeing that they're gaining 10 or 15 pounds. And I think trying to help mitigate some of that weight loss with counseling and helping them out with the dietary advice, potentially medications if they qualify.

Dr Cross:

And the other comment that I was going to make is that I've heard Tina Ha say that weight is one of our biomarkers in IBD. And it doesn't mean that someone who's normal weight or obese can't have really bad Crohn's or really bad ulcerative colitis, but the underweight patients, the patients whose BMI is very, very low are those that are losing 5%, 10%, those are ones that we need to particularly worry about because they're now becoming really our outliers in the IBD population.

Well, how does obesity impact outcomes in patients with IBD? Does it drive activity, severity? Does it depend on disease type?

Dr Kelly:

I think both. It definitely has ... There's a number of studies that have showed it leads to worse outcomes and IBD complications. It's interesting, in both UC and Crohn's colitis or in Crohn's appears to be somewhat dose dependent, so to speak. The more obese you are, so the people with the class 2 and the class 3 obesity are more likely to have persistent disease activity, relapses, or flares; for both surgical outcomes when they do need surgery are worse; more problems with wound healing, infection, all the things you would expect in a patient who's having obesity. In ulcerative colitis, we know that those patients who are hospitalized with a UC flare have higher risks of surgery if they also have obesity and longer hospital stays. And when they do need surgery, those IPAAs are much more challenging and their long-term outcomes after a pouch are worse.

Patients with Crohn's will have, especially if they have a lot of visceral fat and central obesity, an increased risk of a really complicated course with penetrating or stricturing disease and more Crohn's-related hospitalizations. I think besides impacting the disease activity severity, it really, for us, impacts the treatment response to biologics. And there are pharmacokinetic studies showing that patients with high body weight, there's increased drug clearance, shorter half-lives, lower troughs, and an earlier time to loss of response. And I think we've all seen this in taking care of these patients, and I think that contributes to some of the increased disease activity and some of the outcomes.

Dr Cross:

And if I remember right, this is off-topic a little bit, but cross-sectional imaging, it probably is overutilized a little bit in IBD, but particularly in the emergency room. But my understanding is they can actually calculate visceral fat to some degree with cross-sectional imaging and the Harvard system, do your radiologists routinely calculate that for you?

Dr Kelly:

They do not. I think as you talk about the MRI enterography, they do not. You can though, and I have not quite figured out how to do it in the system yet, but when you order a DEXA scan, that is the most accurate way to get a body fat percentage. And the DEXA scan can tell you how much of the fat is axial versus in the abdomen and visceral. It could tell you how much muscle mass they have. And I know there are some freestanding for-profit clinics that do these DEXA scans, and they're highly accurate for giving you a body fat percentage and localizing where that fat is. Apparently you need special software for the DEXA scan, and there is somewhere within the system that we can supposedly do this and bill for it. I just haven't been successful at getting it done yet, but maybe some other centers are already doing that.

Dr Cross:

That's the most accurate way to calculate it. Clearly, you can do the eyeball test when you walk into the office and we have body weight and we have BMI that get calculated. Do you do anything extra in your clinic like waist hip ratios or anything like that?

Dr Kelly:

I've thought about it. I've thought about bringing a measuring tape to clinic, but I mean, you bring this up. This is important. BMI is the best that we have, and it is very predictive for most patients of how much adiposity they have and of obesity, but it can be misleading. And particularly, think of the young muscular guy who's got a BMI of 30, but he's at the gym all of the time. Or you can see it in elderly women who might be really sarcopenic and have a lot of body fat, and they might not weigh a lot, but they have a high percentage of body fat. So you can do measurements. They have different ways to do body fat testing besides the DEXA, some of those impedance tests and things like that. And you can go by body fat, which obesity in men is 32%, or in women, sorry, it's 32% and men, 25%.

But waist circumference is probably easier; if your waist is bigger than 35 for women and 40 for men, that also qualifies as obesity. So that's pretty easy to do. And you can even ask patients if they know their waist. They just have to be measuring in the right place. It's right at the level of the umbilicus and the widest part of the waist, not low down on the waist around the hips.

Dr Cross:

I'm just smiling. No one can see me smiling, but I'm smiling because I have some patients who refuse to get weighed when they come to the office. And I can imagine if we're now going to use the tape measure and measure the waist, that might not be the best for the patient experience scores. But if it's part of your plan and managing their IBD, then I think that's a whole different concept and they'd be more accepting of that if it comes into a comprehensive plan.

Dr Kelly:

Yeah, I think you're right, though. And I think you really can't ignore the fact that this can be very emotional for a lot of people. Some people have struggled with weight or obesity their whole lives, and having themselves weighed and measured can be really traumatic. And so just bringing it up in a way that's compassionate and we’ve got to recognize the biases we have in health care around patients who are obese and just make it a comfortable atmosphere for them. Right now, I have a half a day a week where I'm seeing patients who have IBD with obesity, so they're coming to me specifically to lose weight. So I think it would be easier there where someone's coming to me to talk about it. But yeah, I would say most of my patients, the BMI is just what we're following and it's pretty accurate.

Dr Cross:

So I don't want to say it's extreme, but let's get on the extreme end of weight loss in patients with IBD. So very frequent question in patients that are obese that are thinking about bariatric surgery is “I have IBD, can I have bariatric surgery?” And I think the answer to that varies whether they have ulcerative colitis or Crohn's disease.

Dr Kelly:

Yes. Well, I think for both ulcerative colitis and Crohn's, they favor sleeve gastrectomy over Roux-en-Y gastric bypass. There's not a huge amount of data on this, but what we have from registry studies and some databases show that there are increased postop complications with Roux-en-Y versus sleeve. This is a little tricky, of course, because Roux-en-Y, you have these anastomoses, 2 anastomoses, it's a bigger surgery in a way than a sleeve, but their additional concerns I think with Crohn's is that there were significantly higher odds of having a gastric outlet obstruction subsequently or small bowel obstructions down the road in Crohn's disease patients following a Roux-en-Y gastric bypass. So I'm not even sure if any surgeons are offering a surgery like that to patients with Crohn's. I have seen a few sleeve gastrectomies, mostly in ulcerative colitis patients. I think the big thing is just making careful patient selection, that their IBD is under good control and that you're sending them obviously to someone good and probably doing an endoscopic evaluation before the surgeries just to make sure that there isn't any unrecognized inflammation or something that you would want to treat.

Dr Cross:

Yeah. And I think also the logic for Crohn's is that if two-thirds of patients with Crohn's require resection, if you're doing the bariatric surgery first, then now it may potentially be a more difficult surgery. But also if you're having multiple resections and you're bypassing length of bowel and now you're having resection of bowel, then you're making them predisposed to short bowel syndrome. Fortunately, we see a little less of that now with our new therapies. And then I think for ulcerative colitis, another logic is that it potentially can make a J-pouch more complicated if they have a Roux-en-Y. I don't know. Maybe we worry about that too much.

Dr Kelly:

I would assume so. Yeah. And I mean, I worry about, I mean, we know patients with Roux-en-Ys, even if they don't have Crohn's, have to be on vitamins and iron lifelong, there's already malabsorption going on and that could end up being worse. I don't know if you worry about absorption of medications as well, like your extended release tofa. And is that something that down the road, would that make treatment with those medications less effective or more difficult if you're bypassing this much absorption?

Dr Cross:

Yep, I agree. And I think that my patients that have had sleeves have done pretty well and not had major problems, knock on wood.

Now, I want to give you my script when a patient asks me about a GLP-1, which are all the rage, and I'd say, I would argue, life-saving for many patients. "Dr. Cross, what do you think about me starting one of these drugs?” Just name one of them, whatever. "And I say," I'm very supportive. In my patients, I've seen them have excellent outcomes, not only in your weight, but anecdotally, I think the IBD is easier to control; your bowel movements are less, and people are happy, but you're starting something that has GI side effects like early satiety, nausea, vomiting, altered bowel habits, and you just need to be aware that that could be the drug and it may not be your Crohn's. And I think as long as you're aware of that when you're starting, I'm a hundred percent on board.”

So in someone who's dealing with IBD and obesity as part of your specialty, what other things should I be talking to them about?

Dr Kelly:

I do say these drugs are very effective for most people, but for some reason, about 10% of patients don't respond, and that's always very disappointing when you have someone who's on the highest dose GLP and they're not losing weight. We don't understand exactly who those people are, but it seems to be more common in men to have a nonresponse and in people who have a lot of insulin resistance, diabetes, fatty liver, also people who tend to have more of a binge eating type or emotional eating.

But setting that, I say we start low, we start with low doses. You do not have to dial up to the maximum dose and just go up month by month; if the patient is losing weight and feeling that their appetite's controlled on whatever dose you're on, you can stay on that dose until you hit a plateau, and then I usually notch it up from there. And so in my experience, there are people who only get up to mid-level doses and lose a whole lot of weight and other people who have to go to the top, but it's very ... I try to individualize it for people.

You also have to talk about the cost. I mean, we had recently in January, a lot of the Massachusetts Blue Cross plans dropped GLPs for everything except diabetes. And so I had patients who had been doing really well and lost a lot of weight, and all of a sudden the drug's taken away from them, and we know people regain about two-thirds of the weight in one year after stopping, and so they really should be considered a long-term. We don't know about lifelong yet, but it at least seems like now for the foreseeable future, these are medicines that people are going to have to be staying on.

And so talking about that, I do have some people who come in, I don't know if you've seen this, where they want to lose 10 or 15, 20 pounds, and then they say, "Well, I'll lose it with the GLP, and then I'll just stop taking the GLP and I'll keep it off. I'll just know how to eat." And that really doesn't work. There's more to this than just the calorie deficit and the energy in-energy out. I've had patients who, when they lost coverage said, "I'm going to eat exactly the same, and I don't care how bad my appetite is, I'm going to thug it out with my willpower and eat the same so that I don't gain this weight back." And they would gain 5 to 10 pounds in a month. And I think that has to do with some of the metabolic effects of these drugs, just the difference it has in insulin resistance and some fatty acid oxidation, beneficial effects there.

So we talk about affording it. I always try to put it through insurance, but unless… there are certain weight-related comorbidities that we'll assess for, so if someone has snoring and they haven't had a sleep apnea test, I'll send them for a sleep study. I'll check for fatty liver. I'm actually doing a lot more, even in patients with normal LFTs or high-normal LFTs, doing FibroScans. And I've actually found 2 patients of mine who had longstanding obesity that had F4 fibrosis that was unrecognized. So that can sometimes, with the increasing applications and FDA-approved indications for these drugs, you can sometimes get it covered for those comorbidities and certainly diabetes.

Dr Cross:

So I already mentioned anecdotal experience with patients who are using these. And you mentioned, do I have patients that stop? Certainly I have patients who stop, but I think more common is patients are trying to find that minimum dose they need to stabilize where they're doing once a month or every 14 days or something like that. I think that's more common and they're rationing to try to just find that. And it seems like they can find a sweet spot there where they can maintain.

Dr Kelly:

Absolutely. Yeah, there was a study actually that just came out last week where they were looking at every other week dosing. So when you got to goal weight, then everyone's dosing was extended out to every 2 weeks, and they not only maintained the weight loss over a follow-up of a year, but they actually lost a little bit more weight and their overall muscle percentage went up. So their weight stabilized and the composition became better. So I think that there's not a lot of maintenance studies out yet, but I think from a cost savings perspective and for myself, just being on what the lowest effective dose to control your obesity is I think worth trying to do.

Dr Cross:

So here's the question. What's the program where you can basically bet on anything? It's that computer system that you can keep investing on the odds of this happening. So if you had to bet what's going to happen with Lilly study combining a GLP-1 with a IL-23 inhibitor? So do they make the IBD better?

Dr Kelly:

Well, anecdotally, as you said, you've seen patients where that seems to be the case. I've had this clinic going a little over a year, and it does seem that patients who've been sent to me who are pretty much not quite in remission, not somebody you would change drugs over, but they're mostly there. A little bit of erythema and erosions on the colonoscopy, fecal calprotectin just still a little elevated, so they're not in a deep remission, but they have this factor, this obesity factor that I can address. I've seen when they lose the weight and then have subsequent follow-up biomarkers improve. I've seen colonoscopy actually histologically remission in people who a year before didn't have that. So I think that there are ... I think knowing what I know about how much obesity influences inflammation in the body, and particularly that visceral obesity, these fat cells are producing a lot of inflammatory cytokines that are directly related to IBD, and I can't see how it wouldn't help the IBD to have less of that floating around.

So yeah, I’m very excited about that study.

Dr Cross:

Just as a follow-up, do you think it's only going to be any overweight and obese or do you think it's an all-comers?

Dr Kelly:

I honestly think that with time, the indications from these drugs are going to expand because they do seem to have such beneficial effects throughout the body metabolically and on inflammation. And so I think… I mean, you'd have to be probably talking microdosing here, because if you have someone who's a normal body weight or a lower body weight, you really can't add something and have them losing weight. I think that there will be those studies, and I tell patients who come to see me, some of the people who come aren't quite meeting a criteria for a GLP, which we should probably review is obesity with a BMI of 30 above or 27 with comorbidities, 27 to 29 with comorbidities. But I'll have people who, women in particular, their whole life, they've had a BMI of 21, 22, they're perimenopausal, now it's 26, so they're just reaching into the overweight category, but they're not comfortable there.

I think with time, it might be considered more acceptable with more data to treat these patients as well, and that they would be happier and potentially healthier. I know as people lose weight, just the people have told me they just feel less inflamed, they feel less achy, they feel overall very improved on these drugs independent of just the weight loss.

Dr Cross:

I think it's going to be, forget anti-TNF and thiopurine, I think this is going to be our new combination therapy for the bulk of our population. That's my prediction. I'm not going to invest in the stock, but I think that's going to be a combination.

Dr Kelly:

Well, I would certainly do this. Now we're doing these dual biologics. And if I had a patient who was on something and mostly controlled and I was having a choice between adding another biologic and trying to get them on a GLP if they were obese, I think I would do the second thing.

Dr Cross:

I think you're going to be proven correct, I think.

All right, before I ask you our fun question, I just want to remind the listeners that we are the official podcast of the AIBD Network. We're available on Spotify and Apple Podcasts. Our next AIBD regional is going to be in Portland, Oregon. First time we're going to Portland, May 30th through May 31st. My codirector, Tina Ha, will be there at that course.

What about special populations? So thinking pouches, patients with peristomal hernias, patients with ileostomy and poor function—is there a role for GLP-1 agonists there?

Dr Kelly:

Actually, I had a patient recently who did really well. He had some dysplasia, and so I was sending him for a colectomy and a pouch, but he had a BMI of 40. And colorectal, we had some time and we said, "Can we get him to lose some weight before the surgery?" And he's done extremely well with a GLP, got his BMI down to around 32 around the surgery, and surgery went very well and his pouch is functioning very nicely. So I think if you do have the time to optimize patients prior to pouch surgery, we know that these are technically ... When someone's obese, this is a technically difficult surgery, and their overall odds of having a successful functioning pouch are lower. So I think if you can mitigate that a little bit-- same thing with stomas. There's being obese is a risk factor perioperatively for surgical risks, wound infections and such, but also stoma retraction and parastomal hernia. And so trying to, if you can, help patients lose some of that, especially when there's a lot of abdominal obesity, weight loss, I think, prior to surgery, if possible.

Dr Cross:

And I think the other thing with pouch patients is sometimes when a pouch is created, their normal weight or thin, but then they gain weight after that. And I've seen patients have problems with their pouch with the weight gain, so I think that would be another indication to potentially intervene. And I had a nurse practitioner who I take care of who had a port and was getting fluids a couple times a week. And on a GLP-1, her output got to the point where the port's gone, she doesn't need fluids anymore. It's really been remarkable as far as helping to reduce her ostomy output. So a good success story. And she also lost some weight, which she didn't really have a huge problem with her weight, pardon the pun, but she lost weight as well and feels really good.

Dr Kelly:

Yeah, I think anecdotally, I think even patients, my IBS-D patients are doing better just because you have the slows the motility with the GLP and they're like, "Oh, that's cured. I'm having formed stools now." I think just even outside of IBD as a gastroenterologist, there's so much that obesity impacts. I mean, so many of the GI cancers are obesity-related, our patients with really bad GERD, the fatty liver, of course. And I really think that this is kind of our wheelhouse. These GLP hormones, these are gut hormones. When I was studying for the obesity boards, I'm learning all of these feedback hormone loops, and I was like, this is something GI should really step up and own.

And I feel really, not to be on the soapbox about this, but we have all these other things that we consider routine health maintenance in our IBD patients and talking to them about smoking and getting their DEXAs and their vaccines, I think adding, addressing weight and addressing their obesity. And this is just too many patients out there for the primary cares and the weight management clinics to take care of them all. And in particular in IBD where we're oftentimes the only doctor that our patients are seeing or seeing more than their other doctors, I think that we should get comfortable with these and step up and use them.

Dr Cross:

What's your fun fact?

Dr Kelly:

Ooh, well this is kind of fun. This is really a happy fact is that I lost 80 pounds on tirzepatide. So that's one of the reasons that I got so interested in this. And I've maintained now for a year. I've been the exact same weight for a year, which has never happened to me before.

But my fun fact, I actually found a half-brother in Texas through ancestry.com DNA.

Dr Cross:

Wow.

Dr Kelly:

And that was crazy.

Dr Cross:

We have not had that one before. That's musicians, chefs, athletes, but that's a new one. Colleen, this has been really great. I mean, I learned a lot. I don't want to throw shade on our other guests, but I don't think I've had an episode where I've learned as much, so I really appreciate you doing this.

Dr Kelly:

That's sweet. Thank you.

Dr Cross:

And hopefully we'll have you back for another episode.

Dr Kelly:

Thank you so much. I enjoyed it.