Maximizing Weight Loss & Minimizing Side Effects With GLP-1

Dr. Buse:
Combined with changes in diet and increased exercise, starting and maintaining a patient on medication can be challenging in the management of obesity. Today we’re joined by an expert in the field who will share some of the keys to doing this successfully.

Welcome to Diabetes Discourse on ReachMD. I’m Dr. John Buse. And joining us for a discussion on GLP-1 receptor agonists and how they can be utilized to maximize weight loss is Dr. Ania Jastreboff. Ania is an Associate Professor of Medicine and the Co-Director of the Weight Management and Obesity Prevention Program at Yale School of Medicine.

Ania, thanks for speaking with me today.

Dr. Jastreboff:
It’s my pleasure. Thanks for having me on again.

Dr. Buse:
So you’re a global expert and a total rockstar speaker in the obesity space. It’s really a pleasure to get a chance to talk to you again and specifically get your approach on obesity medicine with regards to specifically a focus on GLP-1 receptor agonists and related medications. Fifteen minutes is not going to be enough time, but to start, how do you engage your patients that you’re beginning to work with about the process that you’re going to go through over the following months and years?

Dr. Jastreboff:
Sure. Absolutely. So the first thing that I do is I ask my patients to share their weight journey with me. I want to hear what’s worked, what hasn’t worked, their successes, their struggles, and within that often times patients will share a story where they have tried to lose weight multiple times throughout their life but have perhaps lost weight but then always regained it, and there’s often times shame and self-blame in that story. And that’s when I swoop in and I share with them the story of obesity biology and how their body is incredibly smart and fights back to try and regain that weight. And we talk about the defended fat mass and how we may potentially impact that with strategies like anti-obesity medications or bariatric surgery.

Dr. Buse:
Perfect. Now, GLP-1 receptor agonists aren’t for everyone, and there are other medication options. How do you sort of introduce the topic and get to the first and sort of next steps in the decision-making around a treatment plan?

Dr. Jastreboff:
So the way that I introduce the topic of GLP-1 receptor agonists or nutrient-stimulated hormone-based medications, so various hormones that are combined with GLP-1 receptor, agonist type medications is we talk about how our bodies actually communicate with our brain, how much energy or specifically how much fat to carry, or that the body wants to carry. So, basically, we talk about the fact that there are hormones in our body. They are nutrient stimulated, so they’re secreted when we eat, and these hormones inform our brain how much energy or specifically how much fat our body wants to carry, and these hormones include GLP-1, GIP, amylin, glucagon, all these different types of hormones. And within that I basically introduce the concept of, well, these medications, GLP-1 receptor agonists, or nutrient-stimulated—hormone-based medications, these medications mimic those hormones, and they communicate with our brain to let our brain know that we feel full earlier or that we feel satiated. And patients really respond to that because, again, they’re very much attuned to and aware of the fact that their bodies are fighting back, and here we are. We’re going to give them something that’s actually going to help them with their biology.

Dr. Buse:
For those just tuning in, you’re listening to Diabetes Discourse on ReachMD. I’m Dr. John Buse, and today I’m speaking with Dr. Ania Jastreboff about counseling patients on diet and nutrition as well as the use of GLP-1 receptor agonists for managing obesity.

So you’ve broached the subject of the GLP-1 receptor agonists. If a patient decides that they’re going to go for it, that this sounds like the right choice for them, how do you counsel them with regards to leveraging the biology of these drugs, minimizing the side effects and maximizing the weight loss and health benefits?

Dr. Jastreboff:
Great questions, and John, I agree with you that all of these things are so important to discuss with our patients up front before they start the medications. So there are several things that we talk about. So the patient’s ready, they’re interested in starting one of these medications, so we talk about the biology of how they may be working and if they respond, they’ll start eating less, and really the importance of as they’re eating less to really focus in on making as healthy food choices as they can because they’re going to be eating less, so how can they make food choices or eating choices where they’re choosing the most nutritious food that they can since they’ll be eating less.

We also talk about incorporating physical activity and specifically resistance exercise because if they respond, they’re going to be losing weight fairly quickly, and we don’t want them to lose muscle mass. So, with any of these therapies, whether it’s dietary changes, these medications or bariatric surgery, patients lose both fat, but they also lose muscle, and so we want to retain as much of that muscle mass as we can, so we talk about how to make nutritious choices as well as incorporating physical activity into their day.

Additionally, what we discuss are potential side effects. So, just like for any medication for any disease, it’s really critical for our patients to know what to expect and potentially how to mitigate side effects. So the most common side effects with these medications are gastrointestinal, so things like nausea, diarrhea, constipation, and occasionally vomiting, but we don’t want our patients, obviously, to have especially vomiting, and we can certainly mitigate those side effects by doing certain things. So the first thing is going up on the medication slowly, and that’s something that we can do as providers. So, if we have a patient and they’re experiencing nausea, it’s important to not go up on the dose but to let their body get used to the specific dose of medication that they’re taking before the dose is increased. There’s no need or requirement to go up once a month with these weekly medications. We go up as is appropriate for the individual patient.

Now, in addition to slowing down the uptitration of the medication, there are several things that the patient can do, and so we talk about these before they start the medication. So the first thing is if they’re experiencing nausea or other gastrointestinal side effects, it’s really important to take note that they will likely be eating less, and so if they eat quickly, they may reach that fullness point much more quickly and therefore feel nauseated. So, basically, we advise trying to not eat past the point of fullness, so sometimes that means eating more slowly or leaving the food at the stove rather than on the table where it’s easier to consume more quickly. We also talk about taking note of which foods may exacerbate symptoms. So, for example, if fatty foods result in diarrhea several hours later, then potentially eating less of those fatty foods, especially as the dose is increased, and then finally reassuring the patient that even though they may be eating less at meal times or at specific points of the day where they’re eating, they may want to eat more frequently, so eating smaller amounts more frequently.

So, to summarize for the patient, basically, it’s not eating past the point of fullness, noting which foods exacerbate symptoms and trying to minimize intake of those during the dose escalation, and then finally eating smaller amounts but eating more frequently, and all of those things can help mitigate side effects, and those are all things that our patients can do.

The final thing that I talk to patients about is that a majority of these side effects occur during dose escalation. So as the doses of medication is being increased. Once the patient reaches a specific dose, and reaches a weight plateau, then often times the side effects lessen over time. So it’s not that they’ll experience these side effects if they have them forever, but that they’ll likely experience them as the dose is going up, and then the side effects will decrease over time.

Dr. Buse:
That’s really a beautiful soliloquy explanation of the conversation. You know, one thing that I would add that’s just a slight bit more specific is I suggest to patients that when they serve themselves to eat, whether it’s from the pot on the stove or whether it’s a meal that they order at a restaurant to try and serve themselves somewhere between a half a cup and a cup of food, to try and eat that slowly and then decide at the end of that whether they’re still hungry, and whether they need to get more. So as we’ve talked about before, I’ve actually used these drugs, I mean personally, been taking these drugs for the last year and a half, and I found it remarkable in the beginning that sometimes a half a cup of food was enough. I had no desire to eat any more food. I never had any nausea, but I think that’s largely because I never ate very much at one time. Everybody’s experience is different, but that is sort of my most frequent tip of the day for patients that I’m starting on GLP-1 receptor agonists.

Dr. Jastreboff:
And, and I agree which wholeheartedly. Putting less on your plate or taking less in terms of the first the first part of the meal is critical, and I think that that’s a great way that you devised that then helped you to not feel nauseated. And many of our patients don’t have those GI side effects and don’t necessarily feel nauseated because, as you said, up front they make certain changes, knowing that they may experience the side effects. Often times if the side effects occur, it’s within day one to three after taking the weekly dose, so especially focusing on those initial days, but then as the medication reaches steady state in their, in their body, it’s less prominent on those days, you know, one to three, but I think your strategy is a very, very good one.

Dr. Buse:
Yeah. And, the other thing that I try and both tell primary care audiences or people that are inexperienced in prescribing these drugs and patients is, you know, from the way people talk about these drugs, you’d think that everybody gets nausea. Well, in fact, it’s only about half the patients ever have nausea. And for most of those patients, it’s one or two episodes over those first few months of titration. So, many people’s experiences is really quite mild. What we’re talking about is things to do to minimize the risk that people will have a bad experience early on so that we can keep them on the drug in the long run.

Dr. Jastreboff:
Yeah. I agree with that as well, and it’s so true. And obviously, if the patient is not having side effects, then that’s not something that we have to mitigate. So, as you said, we focus on strategies if the side effects occur. And one other key thing that we haven’t mentioned yet is the critical importance of starting at the lowest dose when a patient is naive to these medications, when they haven’t had any exposures, and so, really, if we start with the lowest dose, allow their body to get used to it, that’s really critical. If you’re switching between the medications, then depending on what dose they’re taking, they may be able to start at a slightly higher dose but always critical to start at the lowest dose. And if the medications are discontinued for any reason, during the course of treatment, then, again, going back to those lower doses rather than restarting at the highest dose where they’re more likely to experience side effects.

Dr. Buse:
Ania, thanks so much. Do you have any final thoughts that you’d like to share with our audience?

Dr. Jastreboff:
I think the critical and most important thing is obesity is a chronic disease, and we need to treat it with interventions that target disease mechanisms, and I think that these nutrient-stimulated hormones, these GLP-1 receptor agonists, and combination medications really do that. They treat the mechanisms of obesity, and they allow our patients to reach their weight and health goals by treating the underlying disease.

Dr. Buse:
Thank you so much. This has really been a very impactful conversation. On behalf of the audience, I’d like to thank Dr. Ania Jastreboff for being here and sharing her insights on the role of GLP-1 receptor agonists in managing weight loss.

Ania, thanks for joining us.

Dr. Jastreboff:
Thanks for having me. My pleasure.

Dr. Buse:
For ReachMD, I’m Dr. John Buse. To access this episode and others from our series, visit ReachMD.com/DiabetesDiscourse where you can be Part of the Knowledge. Thanks for listening.