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Departments of Medicine and Pediatrics
Harvard Medical School
Obesity Medicine Physician Scientist
Neuroendocrine Unit and Pediatrics
Department of Medicine
Massachusetts General Hospital
Fatima Cody Stanford, MD, MPH, MPA, MBA, has disclosed that she has received consulting fees from Calibrate and Novo Nordisk.
How should glucagon-like peptide-1 (GLP-1) receptor agonists for obesity be dosed? Can a patient taking a GLP-1 receptor agonist start additional weight-loss pharmacotherapy? In this commentary, I answer these and other questions from learners who participated in the live webinar, “Obesity Management Strategies That Can Reap the Benefits of Long-term Weight Loss.” The downloadable slideset from this webinar is available to share with colleagues.
If a patient plateaus on a GLP-1 receptor agonist, is there any recommendation to add another medication, such as an oral medication, to get the weight loss started again?
Absolutely. You could use combined pharmacotherapy, and obesity medicine specialists across the country do this all the time. You may start a GLP-1 receptor agonist, and you might decide that this patient also could benefit from phentermine and topiramate. Remember, those act in 2 different ways on the brain. Phentermine stimulates norepinephrine reuptake in the hypothalamus. Two of the topiramate components stimulate gamma aminobutyric acid receptor. So, you want to make sure that you are using different agents from different classes and avoid duplicative agents. For example, you would never put 2 GLP-1 agonists on board.
If the patient has neuroendocrine carcinoid tumors, can you use a GLP-1 receptor agonist?
Yes. The only contraindications to GLP-1 receptor agonists are a personal history of medullary thyroid cancer and a family history of multiple endocrine neoplasia type 2. So, if it’s not 1 of those 2 things, based on the data and case reports that we’ve seen, you can use the GLP-1 agonists without any issues. We’ve not seen any data that would indicate carcinoid tumors being an issue.
What dosing is best for GLP-1 receptor agonists?
The GLP-1 receptor agonists for obesity have specific indications and dosages. If you look at the package insert for liraglutide, you would start liraglutide at 0.6 mg daily, which would be the first dose on the pen, and you would stay there for 1 week. You would then go from 0.6 to 1.2 mg daily and stay there for 1 week, then 1.8 mg daily and stay there for 1 week, then 2.4 daily mg and stay there for 1 week. And then finally, the treatment dose for obesity is 3.0 mg daily, and you want to stay at the treatment dose.
Semaglutide is dosed differently. First, it starts with 0.25 mg once weekly dosing and you would stay there for the first month. Then you would go to 0.5 mg weekly for a month, then 1 mg weekly for a month, then 1.7 mg for a month. Finally, the treatment dose of 2.4 mg weekly would start at month 5 and continue. There is an actual titration schedule for the GLP-1 receptor agonists.
I will say that the number 1 issue that people have with GLP-1 receptor agonists is nausea. So, for example with liraglutide, a patient may be fine at 0.6, 1.2, and 1.8 mg daily, but when they get to 2.4 mg daily, they have extreme nausea. At that point, I have them back down to the dose that precedes that (1.8 mg daily), and stay there for an additional week before rechallenging with the higher dose. Hopefully, that gives you a way to mitigate some of the issues you might run into.
What are your thoughts on the use of GLP-1 receptor agonists as an obesity management strategy? Answer the polling question and share your thoughts in the comments box below.