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Body Weight: Match, Set, Point?

Randy J. Seeley, PhD

H.K. Ransom Professor of Surgery
Internal Medicine and Nutritional Sciences
Director, Michigan Nutrition Obesity Research Center
University of Michigan
Ann Arbor, Michigan

Randy J. Seeley, PhD, has disclosed that he has received funds for research support from AstraZeneca, Ionis, Kintai, Novo Nordisk, Pfizer, and Zafgen; has received consulting fees from Ionis, Kintai, Novo Nordisk, Sanofi, and Scohia; and has ownership interest in Calibrate, Redesign Health, and Zafgen.

View ClinicalThoughts from this Author

Released: May 4, 2021

To me, it is important to offer treatment to individuals with obesity just like we offer treatments to individuals with other chronic conditions. When we successfully treat an individual with hypertension, we don’t think of them as no longer hypertensive. Rather, we think of them as an individual with well-controlled hypertension. Individuals with obesity should be considered in a similar manner.

Set Points: Individual
Body weight/body fat is subject to biological regulation to maintain a “set point.” Effective obesity medications lower that set point, making it easier to lose weight without having to fight the biological regulatory systems. Once patients arrive at this lower set point, they will stop losing weight. When this happens, many patients will feel that the drug is no longer working for them because they are no longer losing weight.

However, the medication is keeping their set point lower and making it easier to maintain their new weight. Both preclinical and clinical data demonstrate that once the drug is discontinued, patients are very likely to gain weight: The drug was contributing to their weight maintenance.

This is similar to patients with hypertension where discontinuation of pharmacotherapy leads to an increase in blood pressure.

That’s not to say that patients with obesity can never discontinue pharmacotherapy. But as with any chronic condition, discontinuation should be done in the context of an alternative therapeutic strategy, enabling patients to achieve and maintain a healthier weight.

Set Points: Population
In a recent webinar, some people asked, “Why does the population’s set point seem to be going up over time? What is the environmental factor driving this?" These are important questions.

Many hypotheses have been forwarded regarding why obesity is increasing. Are there compounds in our food or environment that interact with the endocrine systems that regulate weight? Is it the availability of relatively cheap, highly processed food? Is it the reduced need for physical activity?

The problem is that this is likely multifactorial—and potentially quite different among individuals. The important point is that for most individuals with obesity, only some of these variables are under their control. Identifying whether any of their medications might be contributing to weight gain, and helping them find a healthier lifestyle that includes good eating habits, regular physical activity, and good sleep hygiene—these are all important steps in the right direction.

But in only a subset of patients is this likely to lead to substantial weight loss. Trying to give patients more tools to help with their weight loss should be a priority.

Preventing obesity on a societal level would be greatly aided by identifying the most important environmental factors that contribute to weight gain. Unfortunately, this is a difficult problem that will not be easily solved in the near term.

Your Thoughts
What are your thoughts on the role of set points in managing weight? Answer the polling question and share your thoughts in the comments box below.

Provided by Endocrine Society

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