Episode Resources

• Episode #57: Weight Loss & PKD: Can It Slow Kidney Growth and Disease Progression?
• Clinical Trial: Glucagon-Like Peptide-1 Receptor Agonist in ADPKD
• Flow Trial Results: https://pubmed.ncbi.nlm.nih.gov/38785209/ 
• Support the Show: patreon.com/PKDDietitian

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Transcript

Hello, hello and welcome to the PKD Dietitian Podcast. I'm Diana Bruen, a registered dietitian (RD) and expert in kidney nutrition and PKD health. Today we're going to explore one of the hottest topics right now, GLP-1 medications.

These meds are also known as and called semaglutide, tirzepatide, and to make it even more confusing, they have different brand names like Ozempic and Wagovy and ZepBound. And unless you have been completely off the grid, you have seen folks online or maybe even person talking about their weight loss taking these medications or perhaps they're better blood sugar management. I bet you didn't know that there's also research around heart health and even kidney protection when it comes to GLP-1 meds.

So today we're going to get into it a little bit of the science, a little bit of my personal experience working with clients on them. We're going to look at what GLP-1s and GLP-1 meds are and even how they work in the body. I'm going to touch on what research shows around their benefits for kidney health.

I'm going to briefly touch on who might qualify and benefit from using them and of course get into how PKD factors in and what the science shows. And stay to the end because of course I'm going to let you know my personal experience as a PKD dietitian after working with several clients using GLP-1 meds for weight loss support and coordinating with their nephrologist. For the sake of making this episode easier to follow, I'm going to refer to the whole group of meds as GLP-1 meds.

So what exactly is GLP-1? GLP-1 in our body is a natural hormone and your body makes it. Everybody's body makes it. It is released generally after you eat but here's the kicker.

This GLP-1 hormone doesn't last very long, only about two to three minutes. Now hormones function in our body as messengers and they send signals to other body parts. GLP-1 is a hormone so it sends specific signals and I will get into these signals and messages in a little bit because that is what is important to know when it comes to understanding how these meds work.

GLP-1 is the natural hormone and GLP-1 meds, the actual long name for that is glucagon-like peptide one receptor agonist. As you can see it's a mouthful so just GLP-1 meds. That's essentially a long way of saying that these medications act and function like that natural hormone.

They bind to the specific hormone receptors meaning that they act like those hormones in the body and the GLP-1 meds come in two main forms. The primary one is a shot form. Folks on it take it once a week because it is long-acting and then the other form which has newly been released is a pill form which people take daily.

There are GLP-1 receptors all throughout your body. There's some in the brain, some in your gut and even some in your kidneys and I'll come back to that kidney part in a minute. GLP-1 meds were first studied over 20 years ago and used to treat diabetes so they've been around for about 20 plus years.

Of course there's a lot of new and different ones on the market now and the reason that they were first looked at for diabetes was because they help regulate blood sugar and the release of insulin both super important for diabetes. What they noticed though was that people who were using them expressed decreased hunger and eventually saw that their weight started to come off desired weight so then they studied GLP-1s for weight loss and this is probably the main reason that you've heard of them because they're everywhere today. You know I even saw advertisements for them dominating the Super Bowl commercials.

This is how GLP-1 meds work as a tool to support weight loss. That signal that they send well there's a couple of them. The first is they send a signal to the brain that turns down appetite so it reduces hunger.

A lot of folks will express this as reduced food noise that always thinking about food or being hungry or the need to eat something. They also send a signal to the stomach that you feel full quicker so you have better satiety. They also send another signal to the stomach that slows how quickly digestion begins and stomach empties.

So folks taking GLP-1 meds experience less hunger, fewer food cravings, and increased fullness and the result ultimately is that they eat less. They are less likely to overeat and they have fewer calories coming in. All of this combined leads to weight loss.

When it comes to GLP-1s and weight loss, I like to think of them as weight management hormone replacement therapy. For clients that I have worked with who have PKD and are using GLP-1s as a tool in their weight loss journey, I find that it creates the space to be intentional about nutrition and it gives them the room to focus on creating healthy dietary patterns. Now there's a lot of work that goes into it revamping relationships with food plus getting back in touch with body cues to support weight management and even intentional movement.

Bottom line, it's a tool in their weight loss journey. As we know being overweight or living with obesity has a negative impact on PKD progression and kidney health. And this is a nice follow-up to the last episode that I did around weight loss and PKD health.

Check out episode 57. It's called weight loss and PKD. Can it slow kidney growth and disease progression? I will link it out in the show notes for you.

I dive more into what the science shows and what research shows around this for PKD. It should come as no surprise that GLP-1s meds are approved by the FDA, the Food and Drug Administration, to help treat type 2 diabetes and for folks living with obesity. Now there are qualifications to be approved for these weight loss management tools.

There's two main criteria. You have to have a BMI of 30 plus, so living with obesity, or a BMI of 27 plus, so overweight with a weight related health conditions such as high blood pressure, high cholesterol, type 2 diabetes, sleep apnea, and even some forms of heart disease. So those are the main qualifications for being approved for diabetes and or obesity.

However, there are other diagnosis with brand specific approvals for treatment. As of January 2025, having chronic kidney disease combined with type 2 diabetes, Ozempic was approved to help treat this. Believe you me, it can get complicated getting the right prescription and insurance approval.

I have definitely been in the weeds with clients working that process before. Again, check out episode 57 to get a breakdown on BMI specific to PKD and what you need to know about the positive effects of weight loss for PKD. Talking about positives, I want to look specifically at the kidneys and what the science shows about GLP-1 meds.

Most of the large studies to date weren't dedicated solely to kidney research. However, looking at these large studies, results were able to be filtered out for kidney health and see how it was impacted and the results showed positive and even kidney protective results. The big trial called the FLOW trial is the one that looked at kidney specific outcomes and this was a clinical trial.

For those of you interested in more information around the FLOW trial results, I will also link that out the main publication in the show notes. The main GLP-1 that they studied in this trial was Ozempic and it was because of the FLOW trial that Ozempic became the first GLP-1 med approved to treat people with type 2 diabetes and CKD. Both the FLOW trial and analysis of all those additional studies have shown that GLP-1 meds have both direct and indirect positive impact on kidney health.

I want to touch on those both. Indirect benefits, these are the ones that are essentially positives that happened when someone was taking a GLP-1 that trickle down had really good impact on kidney health. One of the biggest drivers of this here is the weight loss moving from living with obesity to a healthier weight and when someone loses weight when they need to lose weight, especially when it's carried around their waist, the kidneys are under less stress and strain and the body changes that are good for hidden kidney health include the weight loss, less strain on the kidneys, lower middle fat and visceral fat, so less inflammation in the body overall, lower blood pressure and that is less pressure inside the kidneys and overall lower inflammation and oxidative stress, so less ongoing tissue damage.

If some of these went over your head, absolutely okay. What you need to know is essentially the whole system around the kidneys is working better, so there's less weight, less pressure, lower inflammation and less kidney damage and all of this does really tie back to that positive weight loss. But there's also direct benefits that are being shown to the kidneys and if you recall I mentioned earlier that there are GLP-1 receptors in the kidneys and this translates to potential positive benefits directly to the kidneys themselves, irregardless of weight status.

 What was shown was less protein leaking into the urine, so you've got a stronger filtration and less inflammation, less kidney inflammation, so less tissue damage, lower oxidative stress, so what this means is there's fewer damaging free radical molecules in the kidneys, better blood flow and oxygen delivery to the kidneys and your kidneys love oxygen. Also less scarring, so less fibrosis, long-term better kidney structure and function and we know better kidney structure and function is so important for PKD. So when you put this all together, it looks like GLP-1 medications aren't just helping the kidneys indirectly through weight and blood pressure, they also seem to be calming down some of the actual injury pathways happening inside the kidneys themselves.

 And it's worth noting that the study so far has been focused on chronic kidney disease combined with diabetes, but with these identified kidney-specific benefits outside of diabetic disease, these indications are actually currently being studied. So the direct benefits for kidney health. Now I know what you're thinking, this all sounds great, but what are the risks? Are there any known kidney risks around GLP-1 meds? And the answer is we don't know long-term, but so far there's no direct risks identified, but there are some indirect ones.

And the most common kidney risk is acute kidney injury. This is generally caused by dehydration and dehydration for two reasons. One, if someone has a very severe reaction to the meds and they get side effects like nausea, vomiting, and diarrhea.

And the other is that along with turning off your hunger, the meds also turn down that thirst mechanism. And these are rare, but it is a risk, especially for people who are not educated on the meds and what to expect in their body and how to be intentional with their hydration, or who aren't working with a health care provider for these meds to work well. And then a note for me as an RD, some other risks which may not be specific to the kidneys are that people who aren't being monitored or educated or starting slow and low on these medications do have a risk of rapid and excessive weight loss.

 The goal is not to eat as little as possible. Know this, these meds are not magic. They are a tool.

Taking them does not change what you actually eat. I have seen way too many people who go from overeating not great food to under eating not great food. So just go from larger amount to smaller amount.

That is not the goal. Okay, I had a moment there. Let's look at what we know about PKD specifically.

The research we have now is predominantly preclinical studies. It is animal models, mouse models. The research shows that the GLP-1, specifically semaglutide, delayed cyst growth and PKD mouth studies because it influenced energy and repair paths in a good way.

Very promising information coming out of the animal studies. In the mouse studies, the GLP-1 slowed cyst growth and appeared to improve several energy inflammatory pathways involved in PKD. This matters because PKD kidneys have altered energy use and an altered metabolism.

They also have more inflammation and scarring. So turning down these pathways, changing them for the better, is very positive. When it comes to human studies, those randomized control trials that are the golden standards, there aren't any published yet.

However, there is an upcoming study that is currently, at this time of the episode release, recruiting patients. The study is the second step after animal studies and the animal studies being positive, the human study was approved. A little bit for you about the study in case you are interested in learning more or even participating.

It's based out of Denver, Colorado. The study is going to be a 12-month randomized control trial, meaning that there's going to be a group that gets the GLP-1, which it's going to be terzapatide in this case, and then the placebo group that doesn't. They're going to get it for 12 months and enrollment is specifically for adults who have ADPKD, who are overweight or obese.

The goal is to evaluate the benefits of these GLP-1 medications outside of weight loss. So specifically look at how they benefit PKD. This is a quote from that study proposal.

It says data suggests that targeting improvements in insulin sensitivity and kidney oxidative metabolism, in addition to weight loss, may slow ADPKD progression. You can find out more about the study and linked out in the show notes. I want to add my two cents about these medications, what I've experienced so far in working with clients and people I know personally who are using them.

What's really important to know is that they are a tool to help with weight management and weight loss. They are not the end-all be-all. Look at the risks and look at the benefits.

When working with folks who are taking them, who have PKD, it's primarily for weight loss and weight management in a setting of obesity because the benefits of moving towards a healthier weight, far outweigh the risk that poses to their kidneys and their PKD progression. What's really important is to know how it's going to impact your body, your appetite, your hunger, and be intentional about nutrition moving forward. Also be intentional about the support that you're getting on this journey because again it's not how low can you go with your hunger and your appetite.

It's about creating space and a tool in order to better nourish yourself and create behaviors that support your health goals. So what you want to know ahead of time is a little bit about what I did today, how they work, how you would benefit, what your risks are. Find a practitioner who is supportive to work with you on this journey.

Talk with your nephrologist for additional monitoring if they are open to it. And look into some of the common side effects. I'm not going to cover it here.

 There are some reported side effects but what I can tell you is they can be minimal when you are intentional with your eating and your hydration and with how you approach GLP-1 medications. Bottom line, work closely with a doctor and a dietitian. Have set goals for healthy weight loss.

I like to work with my folks. We check in at least monthly around their weight loss, their eating, their movement. We look at of course all their labs and coordinate with their doctors to do this in a healthy way.

I do believe that the intentional weight loss and moving towards a healthy weight is very beneficial for PKD and I have seen these medications have a very positive impact on this process. I am hoping that we get a lot more information around PKD and kidney health. GLP-1s are not currently a PKD specific treatment but they may be appropriate for some folks with PKD.

If they are something that is on your radar and you believe that they would benefit your health journey, talk to your dietitian, talk to your nephrologist, talk to your doctor. Have a team to support you in this decision and along the path. I hope this was very helpful for you.

I hope you found it valuable and clearing up some of the confusion around GLP-1 medications and until next time, happy and healthy eating. Don't forget, support the show by liking, sharing episode. Make sure to subscribe so that you never miss an episode and if you'd like to support the show more directly, you can do that via Patreon.

I'll link out how you can do that in the show notes.

References 

1. Semaglutide in type 2 diabetes with chronic kidney disease at high risk of progression: real-world clinical practice https://pubmed.ncbi.nlm.nih.gov/35892023/ 

2. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy https://pubmed.ncbi.nlm.nih.gov/39289339/ 

3. Glucagon-Like Peptide-1 Receptor Agonists in Chronic Kidney Disease: Mechanisms and Clinical Perspectives https://pmc.ncbi.nlm.nih.gov/articles/PMC12969668/ 

4. FDA Approves Semaglutide to Reduce Risk of Kidney Disease Progression https://jamanetwork.com/journals/jama/article-abstract/2831055
5. GLP-1 receptor agonists in patients with chronic kidney disease and either overweight or obesity https://pubmed.ncbi.nlm.nih.gov/39583142/

6. Semaglutide in Diabetic Kidney Disease: Integrating Clinical Evidence with Mechanistic Insights https://pubmed.ncbi.nlm.nih.gov/41302309/

7. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials https://pubmed.ncbi.nlm.nih.gov/39608381/ 
8. Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns https://pubmed.ncbi.nlm.nih.gov/38519239/ 
9. Can GLP-1 receptor agonists slow the progression of Autosomal Dominant Polycystic Kidney Disease? https://pubmed.ncbi.nlm.nih.gov/40468228/
10. GLP-1RA Semaglutide Delays the Progression of ADPKD Through Regulation of Glycolysis, Mitochondria Function and Ketosis https://pubmed.ncbi.nlm.nih.gov/40815122/

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