With Widespread Public Interest in Weight Loss Drugs, Which Patients Really Need Them?

In an interview with Pharmacy Times, expert Donna Ryan, MD, discussed her presentation at the American College of Cardiology 2023 Scientific Sessions. Ryan’s session discussed pharmacological approaches for obesity, which patients they are indicated for, and considerations for pharmacists.

Q: Pharmacological approaches for obesity seem to have advanced rapidly in recent years. What are some top options and developments?

Donna Ryan, MD: So, we've had medications for obesity really for the last decade. Beginning in 2012, we got some pretty good drugs approved, but they didn't really produce the amount of weight loss that got the doctors excited about prescribing them until Wegovy (Novo Nordisk). And that drug produces between 15% and 17% weight loss on average in patients who take it. So, it's really been a game changer. Before that time, you know, our medications were pretty good. The FDA requires them to produce at least 5% greater weight loss than placebo, but we have to really use a pretty good lifestyle intervention in order to get 10% or more weight loss with those older drugs. So, semaglutide 2.4 milligrams has been a great success. And the FDA is looking at another medication called tirzepatide (Mounjaro, Lilly), and that medication in its pivotal obesity study showed an average weight loss of about 22%. So, you know, we're getting a lot of weight loss, and it's getting a lot of excitement about it.

I think the reason that weight hasn't been a target for heart disease prevention has been that it's been so hard to produce weight loss and sustain that weight loss. You know, it's not simply a matter of eating less and exercising more. If we're going to get people to lose weight with lifestyle change, it takes a pretty rigorous program, it takes a lot of contact time, and a lot of effort to really produce and sustain even 5% weight loss. So, the ability of these newer drugs to produce more weight loss is a game changer.

Q: How can clinicians know when to make the switch to pharmacologic therapies and when lifestyle changes may not be enough?

Donna Ryan, MD: Well, their patients will tell them. About 20% of patients will be successful with lifestyle change alone, and they can achieve modest weight loss—5% to 10% weight loss, and that's pretty good. But to achieve more weight loss, achieve 10% 15% weight loss, we generally will need medications to help patients do it. Some patients will need bariatric surgery.

We know that these medications will improve blood pressure, they'll improve glycemia. We know that weight loss itself is really good for those things. And we're hoping that we'll be able to show the same benefits that we've shown in diabetes in terms of cardiovascular risk reduction, cardiovascular outcome trials being positive with semaglutide and then also later with tirzepatide. So that hasn't been proven yet, but we have the SELECT trial underway. It should report out sometime late this year, so watch this space for that.

Q: Some of these therapies have garnered widespread attention, but patients may not understand the risk/benefit ratio and other considerations. Can you discuss this public attention and considerations given that?

Donna Ryan, MD: Yeah, you know, I think that the desire for slimness is so culturally pervasive [and] we need to be a lot more accepting of variation in body size, because body size does not always correlate with body health. These medications and weight loss medications are intended for people who need to lose weight for health reasons. So, the FDA indications for Wegovy and all the other weight loss medications are that you have a BMI of 30 or higher, that's generally about 50 pounds overweight, or that you have a BMI of 27 or higher and have a weight-related comorbidity like diabetes, prediabetes, dyslipidemia, hypertension. A serious complication of excess abnormal body fat, which is what obesity really is. So, they're really not intended for cosmetic weight loss.

You know, if we want a medicine for cosmetics, it needs to be absolutely safe. These medications are pretty safe. Wegovy, for example, the class of drugs has been around about 15 years. We know it, we know those GLP1 receptor agonists, and they all have the same tolerability and safety profiles. On the safety side, they should not be prescribed in patients who have a personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia type 2. There's a rare adverse event that occurs with the use of these drugs and that is acute pancreatitis. So, if patients develop abdominal pain and nausea and vomiting, we always stop the drug and work them up for pancreatitis. And if we prove their pancreatitis, we don't re-start these drugs. It's a rare complication. The most common tolerability issues are nausea and vomiting, and about one-fourth of our patients will have problems with that. There are things we can do to help patients get through that nausea and vomiting and in general, it doesn't last very long. And our strategy is usually to use a dose escalation. So, we start low, and we escalate slowly.

Q: Which patients are considered “high-risk” and how does use of pharmacotherapies for weight loss differ for these patient populations?

Donna Ryan, MD: Yeah, well, first of all, everybody has to meet those FDA indications in order to qualify for the medication. So that's a BMI of 30 or higher, that's about 50 pounds overweight, or a BMI of 27 with diabetes, hypertension, dyslipidemia, or, or even prediabetes. So, we want to give these drugs to people who need to lose weight for health reasons. But look, there are a lot of people who have very high BMI, as you know. About 11% of the US population has a BMI of 40 or higher, which actually qualifies for bariatric surgery, that's 100 pounds overweight. So, the prevalence of qualification for this medication in adults is really quite high. About 42% of US adults have a BMI of 30 or higher. So, it's a very common metabolic disorder. Obesity is a disease.

Q: What role do pharmacists play in these treatments, particularly with educating patients and managing adverse effects?

Donna Ryan, MD: The pharmacists are absolutely critical. And I love my pharmacists who help me get these drugs into my patients’ bodies, because these drugs are great, but they can't help the patients unless they can actually be delivered to their bodies. So, pharmacists are very important. They will frequently help with getting access to the drugs. Semaglutide is on the FDA shortage list; it can be hard to get. Frequently, these medications will require prior authorization. So, we'll have to fill out forms and make sure that the patients qualify by BMI and other conditions so that their insurance will pay for them. So, the pharmacists are absolutely critical. My pharmacists helped me with that prior authorization. I wish all pharmacists did, but they're still quite helpful.

Q: How can pharmacists educate patients about these treatments given the widespread attention and resulting questions they might receive?

Donna Ryan, MD: Yeah, so, I think the chief side effect, and it's going to occur in about 25% of patients, is going to be some nausea and vomiting. The pharmacists can help by instructing patients. Patients need to know how these drugs work, and the way they work is in the brain on appetite centers. So, they are going to affect appetite. And patients need to be told, they need to know that you cannot eat the same amount that you're used to eating. If you sit down and have a big plate of food in front of you, and just automatically eat it, you will have some discomfort, you won't feel well. You need to listen to your body, you need to slow down the rate of eating, change what you're eating, don't eat a lot of high fat foods, eat foods that are lower in fat, eat smaller quantities, eat more slowly. And that'll help a lot with the nausea and vomiting. You know, anybody who eats too much will feel nausea. And that's really what's going on in a lot of patients who have the side effects with semaglutide, or even its cousin, liraglutide.

Q: Is there anything you want to add?

Donna Ryan, MD: Yeah, I think that for cardiologists, this is the American College of Cardiology, meaning that weight management is sort of the new frontier. You know, we've been really good about developing good medications to help control blood pressure, to help control glycemia, to help control lipids, but we haven't really addressed a big root cause of cardiovascular disease, and that's obesity. And so, for the first time, we've got some tools in our toolbox to help our patients with their weight. Our patients want to take these drugs [and] we're delighted about that, because I think they're going to have really powerful health benefits.