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Weight Loss Leads to Strong Increase in Appetite—The Body’s Internal Feedback Control of Calories

Studying people in a clinical trial of a type 2 diabetes drug that causes weight loss, researchers discovered that as people lost weight, their appetite increased proportionately, leading to increased calorie consumption and a leveling off of weight loss. The findings provide the first measurement in people of how strongly appetite counters weight loss, as part of the body’s feedback control system regulating weight.

For this study, the researchers sought further insight into why it is so difficult to maintain a lower body weight after loss of excess weight. To investigate whether the body may have internal, biological controls that compensate for weight loss by boosting appetite, they developed a strategy for measuring real-world calorie consumption over the long term in response to weight loss. They examined body weight data from a year-long clinical trial of canagliflozin, a type 2 diabetes drug that substantially increases the amount of glucose (sugar) that is excreted in the urine. This drug causes a gradual decrease in weight, averaging about eight pounds. In the clinical trial, participants were randomly assigned to either the drug or a placebo, without knowing which they received. The participants were not directly aware of the loss of calories in the excreted glucose, and they were not on a restricted diet or in an exercise program. Thus, because the participants were not making intentional behavior changes, the researchers could study what the body is inherently wired to do.

Analyzing data from 153 men and women who received the drug and 89 who received a placebo, the research team calculated calorie intake using a previously validated mathematical model. They compared the measured body weight changes with the weight changes expected based on the loss of glucose calories, and realized that calorie intake increased. For every pound of lost weight, the people treated with canagliflozin consumed about 50 calories per day more than they had been eating before the trial. The increased appetite and calorie intake led to a slowing of weight loss after about 6 months. These changes were not seen in people who got a placebo.

The researchers then analyzed data from a separate trial of a lifestyle weight-loss program for overweight and obese individuals. Based on the weight-loss and regain data, the researchers calculated the compensatory changes in appetite. Although the participants did not maintain their initial diet through the trial, they still consumed fewer calories than expected based on appetite changes—a sign that they persisted in their efforts despite an increased appetite.

These findings underscore the challenges faced by those seeking obesity treatment. Past research had shown that, after weight loss, the body also slows its rate of burning of calories, yet the change in appetite shown in this study is even stronger. Weight loss strategies thus need to overcome the body’s multiple systems designed to regain that weight.


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