Weight Loss Bumps Up Appetite More Than Threefold

Marlene Busko

November 04, 2016

NEW ORLEANS — For every kg of weight they lost, patients in a new study consumed an extra 100 calories a day — more than three times what they would need to maintain the lower weight.

This out-of-proportion increase in appetite when patients lost a small amount of weight "may explain why long-term maintenance of reduced body weight is so difficult," said lead research David Polidori, MD, of Janssen Research & Development, in San Diego, California, and colleagues.

The findings suggest that "a relatively modest increased appetite might explain a lot of the difficulty that people are having in both losing the weight and maintaining that weight loss over time," noted senior author Kevin D Hall, MD, from the National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, in Bethesda, Maryland.

He presented the findings at Obesity Week 2016, and the study was also published in Obesity.

Previous studies show that metabolism slows when patients lose weight, "as recently popularized by our previous studies of The Biggest Loser contestants," Dr Hall told Medscape Medical News.

"However, our new results suggest that proportional increases in appetite likely play an even more important role in weight plateaus and weight regain," he suggested.

However, he cautioned: "These are early days, and it's our first way of looking at this process in humans," so the findings would need to be confirmed.

The study was selected as a top-five paper in a special symposium at the conference, because it gives an "interesting discussion of the physiology that drives weight regain after successful loss," session comoderator Donna H Ryan, MD, professor emeritus at Pennington Biomedical Research Center, in Baton Rouge, Louisiana, and associate editor in chief of Obesity, told Medscape Medical News.

Since the findings suggest that an increased appetite is an even stronger driver of weight regain than slowed metabolism, "the message to clinicians is to not only push physical activity as a way to counter [weight] regain but also use medications that impact appetite," she noted.

And Ken Fujioka, MD, director of the nutrition and metabolic research center at the Scripps Clinic in Del Mar, California, told WebMD, Medscape's consumer-news website: "This is a landmark study. It gives us very useful information that will actually help us develop new guidelines" to prevent weight regain.

"We get patients all the time who hit these plateaus, and we're trying to figure out, what do we do?" Dr Fujioka said. "It's real clear to us that you really need to deal with the food-intake side, the driven appetite, from this paper."

SGLT2 Inhibitors: A New Way to Study Energy Balance

Knowing that patients with type 2 diabetes who receive the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana, Janssen) as part of a glucose-lowering strategy excrete a fixed amount of glucose in the urine (which causes weight loss), Dr Polidori and colleagues used a mathematical model to calculate energy-intake changes during a 52-week placebo-controlled trial of the drug, in which 153 patients received 300-mg/day canagliflozin and 89 patients received placebo.

Using this approach meant that the participants who received canagliflozin consistently excreted 90-g/day glucose but were not aware of the energy deficit, Dr Hall noted.

Previously, the researchers had validated a mathematical model to calculate the expected changes in caloric intake corresponding to changes in body weight (Am J Clin Nutr. 2015;102:353-358). They input the current study data into this model.

At study end, the patients who had received placebo had lost less than 1 kg and those who had received canagliflozin had lost about 4 kg. The weight loss with canagliflozin was less than predicted, due to the patients' increased appetite.

On average, patients who received canagliflozin ate about 100 kcal/day more per kg of weight lost — an amount more than threefold larger than the corresponding energy-expenditure adaptations.

"Our results provide the first quantification of the energy-intake feedback-control system in free-living humans," the researchers write.

They add that in the absence of "ongoing efforts to restrain food intake following weight loss, feedback control of energy intake will result in eating above baseline levels with an accompanying acceleration of weight regain.

"The few individuals who successfully maintain weight loss over the long term do so by heroic and vigilant efforts to maintain behavior changes in the face of increased appetite…in an…obesogenic environment."

And since continued weight loss becomes harder as patients lose more weight, this study reinforces the message that patients should "focus on making healthy lifestyle changes that they can live with over the long term," according to Dr Hall.

The study was supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Disease, using data from a study sponsored by Janssen. Dr Polidori is a full-time employee of Janssen. Dr Hall has applied for a patent on a method of personalized dynamic feedback control of body weight and has received funding from the Nutrition Science initiative to investigate the effects of a ketogenic diet on human energy expenditure. Disclosures for the coauthors are listed in the article.

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Obesity. 2016;24:2289-2295. Abstract

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