Innovations in Weight Loss Management - Episode 7

Pharmacotherapy for Weight Loss

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An in-depth discussion on pharmacologic therapies available to help patients manage their weight, with special insight regarding the prescribing and use of GLP-1 agonists.

Chris Mazzolini: Let’s move on to the pharmacologic agents. What’s currently available? Dr. Christofides, would you mind going through what’s on the market, some of the indications, and the different efficacies of these available treatments?

Elena A. Christofides, M.D., FACE: Sure. I will share the ‘CliffsNotes’ version to you since this is a pretty large area now. In terms of prescription medications that are available, there are numerous ones, but there is one that is available over-the-counter now called orlistat [Alli], that is a fat-blocking medicine, meaning it blocks the absorption of fat in the gut when you eat. It induces weight loss through calorie deprivation and loss of calories in the stool. It’s moderately efficacious. It’s been around for a long time. It was actually out by prescription originally, and then has been felt to be safe enough to be over-the-counter. Prescription-wise, there is phentermine [Lomaira], which is a medication that’s been around again for a very long time, available on its own, alone, or in combination with topiramate [Topamax] as Qsymia [phentermine and topiramate]. Qsymia is a prescription medication that works through suppression of appetite and changes the hunger and eating drive. Not just hunger, but the desire to eat — the bingeing in particular, the late night eating or the emotional eating. There are some very particular elements to that. There’s naltrexone [Vivitrol] and bupropion [Wellbutrin XL] as a combination, known as a Contrave [naltrexone and bupropion]. Neither naltrexone or bupropion, alone, has been approved for weight loss or obesity management and neither has any indications for weight loss or obesity management. But together, as Contrave, has been shown to improve the inflammatory response in the brain, improve the inflammatory reaction in the body, and reduce hunger through loss of the inflammatory instigator of hunger, so there’s a significantly different perception of hunger by the patient. There is also a different sense of well-being by the patient because those drugs are much more neurologically effective and is more on the antidepressant side of the class of medications. There is a bit of a mood change in the attention to eating. Both combination therapies are moderately effective, and are both oral. Actually, all three of what I mentioned, so the orlistat, the Qsymia, and the Contrave, are all oral. They’re all dosages of once a day, except for the orlistat, which is taken with each meal. The Contrave could be once a day or twice a day. The Qsymia is definitely once a day. Those are moderately effective. They’re approved for long-term use, and can be implemented at any point in time, lifestyle management as well, postoperatively, if somebody had weight loss surgery. I’m going to let Dr. Bays explain liraglutide [Saxenda] and semaglutide [Ozempic] because they fit into one category on their own.

Harold Edward Bays, M.D., FOMA, FTOS, FACC, FNLA, FASPC: Right. That’s correct. Liraglutide and semaglutide belong to a group of anti-obesity agents we call glucagon-like peptide-1 receptor [GLP-1] agonists. That may sound intimidating and complicated, but here’s the way I would think about it: If you don’t eat for a while, then your gastrointestinal system responds by releasing hormones that make you want to eat. The flip side is also true. After you eat, the gastrointestinal system releases hormones that help you digest your food, but also tells you that you don’t need to eat anymore. That’s the reason you’re no longer hungry. To exploit those hormones that are normally made by the body, we have these agents called glucagon-like peptide-1 receptor agonists, or GLP-1 receptor agonists. Two GLP-1 receptor agonists are approved for the treatment of obesity, liraglutide and semaglutide. The thing to know is that these drugs are not just used for treatment of obesity, but they’re also used for treatment of the diabetes mellitus. That can be confusing because if you start looking at the prescribing information, the doses are different, the frequency of administration is different, and the type of administration is different. For example, semaglutide also comes in a pill for the diabetes mellitus. I would caution clinicians to be careful about looking at the particular doses for the particular indications. As far as the side effects go, I think you would anticipate what the side effects would be from a gastrointestinal hormone. They would be gastrointestinal side effects like nausea, vomiting, diarrhea and those types of things. Specifically, with regard to GLP-1 receptor agonists, there is a contraindication in patients who have medullary cancer of the thyroid, or genetic conditions with regards to medullary cancer of the thyroid. If a person develops pancreatitis, that’s another contraindication. For example, in rodents, there’s been some suggestion that medullary cancer has increased. We don't know what that means for humans, but nonetheless, it’s in the prescribing information, and clinicians should be aware. An adverse experience for which clinicians should be aware of with the use of the GLP-1 receptor agonists would be in patients who have diabetes mellitus because these agents we’re talking about, the GLP-1 receptor agonists, with liraglutide, you’re talking about 5% to 10% weight loss, and with semaglutide you're talking 10% to 15% weight loss. If you know that GLP-1 receptor agonists, or what we call incretins, will increase insulin secretion, or they also affect the brain and diminish hunger and such, it doesn’t take a lot of logic to figure out that if you have somebody that’s being treated particularly with insulin or sulfonylurea, and they have diabetes mellitus, and they start to take a GLP-1 receptor agonist, blood sugar levels will plummet and the patient will get hypoglycemia. It’s very common. If we have a patient come in that’s energized, excited about weight reduction, going to engage in appropriate nutrition and physical activity, to start a GLP-1 receptor agonist, just like we do with weight loss surgery, it’s quite common that we back off the anti-diabetes drugs early on, or at the onset of the GLP-1 receptor agonist administration, because the last thing we need to be doing is creating a problem when we’re trying to fix a problem. I would advise folks that if you have a patient who has a reason to control their blood sugar levels, you’re going to put them on a GLP-1 receptor agonist. And particularly, if they’re on insulin or sulfonylurea, you need to back those medications off from the get-go, and have routine monitoring of glucose. Keep a handle on that. I think that’s going to be your best bet to avoid potential hypoglycemia.

Chris Mazzolini: Great. Thank you. I appreciate it.

Transcript edited for clarity.