Two experts in obesity medicine discuss the latest advances in obesity care and how to best integrate novel obesity management medications appropriately in your practice.
Two experts in obesity medicine discuss the latest advances in obesity care, including:
[JF1]Added this to the episode notes to maybe help with the posttest
Presenters
Amy Butts, PA-C, DFAAPA, BC-ADM, CDCES
Endocrine Physician Associate
WVU Medicine Wheeling Hospital
Immediate Past President of American Society of Endocrine Physician Associates
Wellsburg, West Virginia
Nicholas Pennings, DO
Professor of Family Medicine
Campbell University School of Osteopathic Medicine
Director of Clinical Education
Obesity Medicine Association
Buies Creek, North Carolina
Link to full program:
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This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
Dr. Pennings: We are here today to talk about new and emerging incretin based therapies for obesity medicine. This is a very exciting time as new obesity medications are coming on and the landscape is changing very rapidly. I think what is really exciting about this is it creates an opportunity for primary care providers to be the first point of care in obesity medicine, to initiate obesity therapies. This is really a great opportunity because it is the primary care providers that are seeing the patients first line.
This gives us an opportunity to treat obesity like we treat many other chronic conditions like diabetes, hypertension, dyslipidemia. These are all chronic conditions. Like obesity, they are driven by biology. Amy, you want to tell us some more about some of the newer therapies?
Amy Butts: Sure. Absolutely. Thank you. I could not agree with you more. It is an exciting time in obesity management, and we have choice now and we can decide on what is best for the patient, using a person centered approach and some shared decision making. We are able to really break down for each patient what types of medications are out there and what indications they each have, including comorbid condition risk reduction, like ASCVD that we see now with semaglutide orally and injectable.
Then, of course, we also have indications to help not only reduce weight but improve moderate sleep apnea with medications like tirzepatide injection. Then we now have oral options, which are really great to have as an option for individuals who do not want to take injections or, for whatever reason, they choose an oral version instead. These medications are great in the sense that they allow ease for patients to use as well.
So really the key is selection, and we should not forget cost and the fact that sometimes going back to some of the older medications that we have had for obesity may be the correct choice for an individual where maybe cost is an option, or a problem excuse me, or if we have an issue where maybe they are contraindicated to utilize some of the newer medications. It is exciting time because patients finally have choice in order to really tackle this chronic relapsing disease state we know as obesity.
Dr. Pennings: That is great, Amy, and I think we have got some opportunities to unpack those great points that you made. I want to start by just talking about the mechanisms and the treatment landscape that these incretin based therapies, they target appetite. One thing that I think is foundational in the treatment of obesity is that we talk about eating less and exercising more. Of course, that creates a negative energy balance which allows you to lose weight. The challenge with that is that increases your appetite. You are more hungry and that is not a good feeling.
That is where these medications can really be very effective in targeting appetite. Helping to improve satiety so that you are not feeling hungry all the time when you are calorie restricting. In addition, you help glucose control and lose weight. We now have some really nice options with new oral medications, including a small molecule nonpeptide, that is expanding the options for our patients. This really matters because patients can be very reluctant to do injectables. They are sometimes very hesitant and the option of an oral medication is very exciting.
Amy, maybe you want to talk a little bit more about some of the comorbidities and other components of using incretin based medications.
Amy Butts: Absolutely. I think it is great to talk about percentage of body weight loss. Looking at efficacy and our older obesity medications, although they provided us with a percentage of body weight, nothing like these newer incretin therapies do provide us. If we look at one of the older medications that we used to use, like orlistat, that only really provided a 3% to 5% body weight loss. With the side effects, it was really uninviting or many individuals chose not to pursue something like that for that small amount of weight loss.
Then looking at phentermine, we know phentermine helps patients. However, we are looking at a 5% to 10% weight loss reduction. In individuals we know that are using the higher phentermine dose, it really is not recommended to use longer than 12 weeks. We then moved into an era where we were getting some more medications that could be used for long term management, such as a combination of phentermine and topiramate naltrexone and bupropion.
Once again, although these medications can be used for long term use, percentages of body weight really varied anywhere from 5% to 10%.
Moving into the newer medications that we do have access, we are getting greater body weight reductions, and we are really focusing on shutting that food noise. It is meant for long term management. These are medications that patients can continue to take long term in order to maintain and be successful.
We know that obesity can be a very mental distress for individuals. It is a lifelong struggle, and many of them have been shamed and felt defeated over the years with negative feelings and negative comments being made to them. The fact that with medications like semaglutide, we received anywhere from a 12% to 18% reduction in body weight. Tirzepatide we received as much as 15% at the five milligram dose and 20% to 22% with the 15 milligram dose in SURMOUNT-1.
Then now even with pills, for those individuals that do choose a pill option, the newest drug orforglipron provided a 12.4% reduction in body weight. We are getting some really robust percentages of body weight loss that make a true impact in the patients overall care. I think it is a win and the future is bright. Do you agree Dr. Pennings?
Dr. Pennings: I agree. On top of that mental distress that comes with obesity with the stigma and bias that many of our patients face. The idea of taking an injection can also be very distrustful for patients. So, having some oral options that are really potent, really effective is a very exciting time for us.
Now, oral does not necessarily mean that it is easier. Oral semaglutide requires a very specific type of administration where you have to take it in the morning on an empty stomach with no more than four ounces of water and only water, and then waiting 30 minutes before you eat any other food, beverages, or taking other medication. There is some challenges around using the oral medications. The orforglipron now has an option of taking the medications with food, so that is an exciting new addition that we are seeing today. Would you agree, Amy?
Amy Butts: Absolutely. I think that is the one thing that separates orforglipron from semaglutide oral is the fact that the convenience of this pill. That really definitely was sometimes an obstacle for my patients with timing with the oral semaglutide. The fact that an individual can get up in the morning, they can take that pill with or without food, and there is no problem with timing. They can leave the house. Get onto their day. I am a busy working mom, and so I know what my mornings are like. It is really nice to have that option for those patients.
Dr. Pennings: That is nice. You mentioned about all of the different outcomes that we saw in the different trials. Of course, you cannot compare head to head unless you do a direct study and that has been done with tirzepatide and semaglutide. With many of the other medications, we do not have direct head to head studies, but we see significant weight loss with all of those medications. I think that is really exciting.
One of the things that is also a little bit confusing sometimes is we hear reports of different percentages of weight loss. Part of that is based on the design. There is something called estimands that are used to calculate the average weight loss that patients are experiencing. There is the treatment policy estimand and the policy product estimand or efficacy estimand. These are ways of calculating how many patients lost weight or what their percentage of weight loss was. The difference is really the treatment policy estimand you will see the percentage of patients that have lost weight, that started the medication and what the average weight loss for all the starters were.
I distinguish it between the starters and the finishers. The treatment policy estimand looks at how many people started the program and what was their average weight loss at the end. Whereas the efficacy estimand look just at the people who completed the treatment protocol, according to the protocol, and were able to finish the right to the end. What was their average weight loss? That is often higher. That represents our patients that are able to go on the product, stay on the product, and so that could be a little bit confusing. We see sometimes with the oral semaglutide, the treatment estimands or the efficacy estimand of almost 17%, which is quite impressive. Both of those, both oral semaglutide and orforglipron show clinically meaningful weight reductions, which is very helpful for our patients.
Amy Butts: I agree. I think the messaging really is that it is not a one-size fits all for every single individual. I think the messaging is that we now have powerful options that will make an impact on our patients' lives and reducing their comorbid conditions. Unfortunately, we live in a world where sometimes we are more focused on the number of on the scale or the percentage of body weight loss versus the impact that even 5% to 10% of body weight reduction can do for us as far as reducing our cardiovascular risk.
Having that conversation, we as providers, having that conversation with our patients, making sure that we explain to them that it is more than just a number. The fact that these trials support, that we have products in the world today that can fit into anyone's lifestyle, that will give them impactful, meaningful results in the long term.
Dr. Pennings: What are some of those conditions that you are looking for to treat with weight loss?
Amy Butts: As I spoke to earlier, first of all, we know that atherosclerotic cardiovascular disease, a patient 5% to 10% body weight reduction can impact and reduce that risk. We know that when it comes to the benefit that we see with joints and physical mobility, even a 5% to 7% can make a huge impact on individuals. MASH, fatty liver disease, metabolic dysfunction-associated steatohepatitis. We know that we are seeing impact with 5% to 10% in these individuals as well.
Once again, it is these comorbidities that it is not just the number. It is the comorbidities and how we can reduce patients from developing cirrhosis of the liver and patients developing the need to have open heart surgery or their 12th stent. We really need to move the mark and looking at that and reminding them as we age our goal is to slow the progression of these events. Doing this by helping them with the weight loss will impact them.
Dr. Pennings: Yes, it is sometimes said that obesity is the mother of all diseases and there are so many diseases. Some estimates of over 200 different diseases that are caused by or made worse by obesity. You listed a number of them. But also the quality of life really matters for individuals too. When we are treating these diseases and we are helping people get healthier, that is something I really enjoy about obesity treatment is the quality of life improvements.
Choosing a new medication can be challenging, and sometimes, particularly for a medication like the treatment of obesity, I think shared decision making is such an important part of guiding patients and working with patients, and making sure you are finding a treatment option that fits best into their lives.
There is a framework that we use for this called the five C's. That is sometimes very helpful. First identifying contraindications and cautions that should be used. Are there specific conditions that the patient has that would pose a contraindication or something we need to be careful about, something in their history. Also, what are their comorbidities? You listed a whole bunch of things like blood pressure and diabetes and sleep apnea and MASH. These are all important. They help us to decide what medications might be ideal for this individual.
But also listening to the patient. What are their thoughts about medications? What are their fears and concerns about medications, either the type of medication or the route that we are giving it to them? What other medications, are they on? Are they on certain medications that might be promoting weight gain? We should always be looking for those medications. Then what combinations of medications might be beneficial? Perhaps if they have a condition such as depression, you might be looking at a medication that contains bupropion that might be appropriate for that patient. If they are on other medications for depression, we want to be concerned about those things. These are things that weigh into our decision making.
Then finally cost and coverage is the last C. Medications can be expensive and coverage is spotty at best, but it is nice that we have some options that are more cost effective. Some of the pricing options have come down, which is beneficial.
What do you look for in underlying diseases in patients with obesity, Amy?
Amy Butts: I definitely always assess cardiovascular history. I look at hypertension, dyslipidemia, diabetes. Does the individual have obstructive sleep apnea? Do they have MASH? Do they have mobility issues? Based upon those factors and those phenotypes, I then look at what medication best targets or has that proven indication or proven benefit in clinical trials.
As I have said earlier, once again, semaglutide has been found to reduce risk with individuals who have established ASCVD. We know tirzepatide has been shown to be beneficial for those who have moderate obstructive sleep apnea. Semaglutide injection has been shown to provide benefit with MASH. Really our goal is to help patients and utilize medications that we know, provide that secondary benefit, not just the number on the scale.
However, unfortunately, as you spoke to cost and access. We are seeing some coverage occurring in individuals for obesity if they have obesity with one of these comorbidities. I have been successful at getting semaglutide covered for individuals for the ASCVD. I have had a few individuals with the tirzepatide approval with the sleep apnea. But not all insurances. We still have barriers. We still have work to do as far as finding access for our patients in this space.
However, as you spoke to, there are a lot of cash options these days. These newer agents, all of the pharmaceutical companies are competing and at this point all have direct manufacturers. Individuals can purchase these medications directly through their pharmacy at lower cost. It seems like every month the prices are getting a little bit better every time.
However, we know that these cash prices are still sometimes not affordable for individuals, especially in the areas where we know social determinants of health is such an issue. I work in the state of West Virginia. Unfortunately, we live in a low socioeconomic area. I am utilizing older medications in some situations. Not as a first line option, but something is better if I can get some benefit for my patient, I have to choose older options. When a patient asks me, "What do you think is the best medication? "I always say, "It is the one that you can afford to take." As I have said earlier, not a one size fits all. Really meeting the patient where they are in their socioeconomic status.
Dr. Pennings: That is a great point. The newer medications that have come out in oral form also have a lower price point, so that also creates some better affordability. It is also important to remember that just because they are oral does not make them any less effective. It really is impressive the effectiveness of these oral GLP-1 agents. They can have an equivalent response to the injectable forms. That is really nice to see.
We also need to make sure that our patients do not have any contraindications. I mentioned that earlier, but some of the specific things we want to look for with the GLP-1s is, is there a personal or family history of medullary thyroid carcinoma? We would not prescribe it in those patients. Now there is other types of thyroid cancers that it is not a contraindication for, medullary thyroid carcinoma is an unusual form. You need to know whether or not a patient or a family member has that. As well as multiple endocrine neoplasia two, which if they have a personal history of that. For some of the medications, a family history of MEN2.
GI side effects are common with these medications. Fortunately, they are usually not too severe and often transient, so that they will subside over time, and altering the dose escalation schedule can be helpful to minimize those side effects. The side effects sometimes are severe and sometimes can even lead to dehydration from severe GI side effects. That can result in kidney injury. So, we want to be wary of that and warn our patients about that.
With weight loss, we can have gallbladder problems, cholelithiasis, cholecystitis, and it is a little higher with the GLP-1 medications. As well as we want to be concerned about pancreatitis. If they develop symptoms of pancreatitis, abdominal pain, back pain, nausea, vomiting those are reasons to stop the medication.
In our patients with diabetes that are on insulin or sulfonylureas, we want to make sure that we do not cause hypoglycemia as these medications will decrease insulin requirements. We want to be proactive and adjust insulin accordingly if they are on those medications.
Lastly, these medications also slow gastric emptying. We want to be mindful of that and make sure our patients know to alert any of their providers that are going to take them to surgery and work with the anesthesiologist to make sure that they stop these medications with the appropriate amount of time so that they do not have any residual gastric contents and increase the risk of aspiration.
Are there any other things to be concerned about, Amy?
Amy Butts: I think when it comes to the oral medications, it is very important for us to talk about interactions with other medications. What we know about semaglutide orally is that, when individuals are taking levothyroxine, semaglutide was found to increase the absorption of levothyroxine. In our individuals taking that, it is just very important that we monitor TSH levels and adjust medications appropriately.
Some other medications that have a narrow therapeutic window like warfarin, although warfarin is not used as much as it used to, there are some pockets that it is still being used, we need to be careful and cautious with that as well.
We do know that tirzepatide it is important to discuss oral contraceptives. With individuals taking tirzepatide, we know that in the trials they saw a decrease in effectiveness of oral contraceptives.
It is important in individuals taking this. Also tirzepatide, and orforglipron. Both have this contraceptive counselling that needs to be done where discussing with individuals that it can decrease the effectiveness of a hormonal contraceptive. You want to consider a barrier method, especially within those first 30 days after starting the medication. Any time you escalate or increase the dose, it is very important to make sure that these individuals are using a second barrier method, or a non-hormonal form of contraception to avoid any type of pregnancies.
The other thing with orforglipron that is important is there are some caveats with it as well. We know that simvastatin, although we do not use as much simvastatin these days, especially in our high risk patients, we tend to use rosuvastatin and atorvastatin, but there are some individuals still out there that use simvastatin. With this medication, orforglipron can increase the effectiveness of simvastatin, so it is not recommended for patients to be on more than 20mg a day.
We also need to caution use with strong CYP3A4 inhibitors. These can increase levels. These are medications like clarithromycin, ketoconazole, and verapamil is probably one of the more common chronic meds that may be used in individuals. Strong CYP3A4 inducers can reduce the effectiveness of orforglipron. It is recommended to avoid this in these individuals as well.
Dr. Pennings: There is a lot of things to be thinking about. Then also about blood pressure and A1C, we want to be monitoring those and lipids, as well as being able to assess what their mood is. Some of these medications can affect individual mood. I think those are important, but it is also important that we follow dietary interventions.
Amy Butts: Absolutely. That is the foundation. It is very important to remind patients that all of these medications are to be used in addition to lifestyle modifications, including dietary and exercise. We want to focus on reinforcing protein intake. We know that patients when trying to lose weight should be intaking 1 to 1.5g/kg of body weight a day of protein intake. That is anywhere from 80g to 120g for a female and 100g to 150g a day for a man.
We also wanted to talk about fiber intake. We know that these newer meds slow gastric emptying and so we can see those issues like constipation and diarrhea. It is important to also discuss with patients trying to get in 25g to 30g of fiber a day. That can be done either with food or the combination of food or supplements, fiber supplements, but really encouraging that.
Then hydration. These medications, they shut off food noise, but they also sometimes do shut off the desire to drink. We know that acute kidney injury can occur with medications if patients become dehydrated and have severe GI intolerance. It is important to encourage patients to focus on drinking 64oz to 100oz of water a day.
Then exercise. Resistance training, especially in the ageing population we know that we will lose muscle mass as we age, and we also know if we are not intaking enough protein, we can lose muscle mass as well. Encouraging individuals, when participating in activity, to really focus on resistance training, with the goal of it being two to four times a week, at least 20 minutes. 20 to 30 minutes would be ideal. That is not only for muscle wasting, but improving balance and reducing fall risks.
Do you have anything else that you tell your patients, Dr. Pennings? Is there anything that you would add that I have not brought up?
Dr. Pennings: No, I think you cover that quite well. We definitely want to avoid frailty, particularly in our older patients. That exercise component, that adequate protein intake, and understanding that patients that are elderly have a decreased bioavailability of proteins. They have an increased protein requirement. I think those are all very excellent points.
We often think about decreasing hunger. We do not always think about decreasing thirst, and that is an important point that you made, that we want to make sure our patients are drinking enough.
With these new therapies, it is really very exciting that I think it creates a great opportunity for primary care providers to be able to treat patients with obesity early on. But really take on that patient centered approach, combining it with lifestyle therapies, and also being able to initiate therapy early on.
Amy Butts: I agree. I think the point is we as the provider, being proactive with our patients and really asking for permission to discuss their weight. Not only for that external appearance, but what we know that obesity, the impact that obesity has on our overall health, and our long term complications and decline. I enjoyed so much speaking with you today, Dr. Pennings. You are such a joy and such a pleasure and a wealth of knowledge. Thanks for including me on this podcast.
Dr. Pennings: This was a great discussion and I think this is a great opportunity for our primary care providers to be able to take that proactive approach, but also to make sure that it is part of a comprehensive treatment plan that includes long term care for obesity. It was great talking with you today, Amy, and look forward to talking again sometime.