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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.
Why should pharmacotherapy for obesity be continued indefinitely? What role does metabolic adaptation play in weight regain after bariatric surgery? 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. For answers to questions on glucagon-like peptide-1 (GLP-1) receptor agonist use in patients with obesity, see our companion commentary.
Can you explain why pharmacotherapy for obesity should be continued for the remainder of the patient’s life? If the patient’s weight loss plateaus or they reach their goal, why not stop therapy?
With weight loss pharmacotherapy, different pathways in the brain are affected. If I discontinue the drug, that impact on the brain is lost, and I can guarantee you 99.99% (because nothing is 100%) that patients will regain their weight back to where they were prior to the initiation of the weight loss agent. As you expect patients’ blood pressure to increase if they stop taking an antihypertensive, this is exactly the response we see with antiobesity pharmacotherapy. This is why when you are treating the chronic disease of obesity, long-term use of pharmacotherapy agents is indeed necessary.
When patients have bariatric surgery and 85% of their stomachs and ghrelin-secreting cells are removed, why do some patients regain the weight? Is pharmacotherapy indicated in this instance?
Medication as an adjunct therapy for inadequate weight loss or weight gain is not off-label use. After surgery, many patients, even at their nadir (usually 12-18 months post surgery), do still have obesity because they typically start with severe obesity, so you can use pharmacotherapy. However, neurons responsive to ghrelin are housed in the hypothalamus. We did not cut out the brain and so ghrelin, the hunger hormone, begins to take over in the brain. We know that immediately after surgery, GLP-1 goes up dramatically, but over time it begins to titrate off. Many hormonal changes, and not just the reduction in stomach size, affect weight and the body can become accustomed to those changes. Once we start to see the weight curve going up, we want to add pharmacotherapy agents—of which there are several—to get additional weight loss and help the patient to maintain their weight before any significant regain occurs.
Is there a way to give a patient brain-derived neurotrophic factor?
No, but it would be great if we could. High levels of brain-derived neurotrophic factor lead to leaner phenotype, but we do not have a way of giving that. We do have a way of stimulating the brain to deliver more brain-derived neurotrophic factor by using GLP1 to help stimulate the specific pathway to the brain, resulting in increased brain-derived neurotrophic factors.
How do you address metabolic adaptation and weight regain in patients after bariatric surgery? Answer the polling question and join the conversation in the comments section.