Dual regimen targeting appetite and energy expenditure enables lasting weight loss

Diet and lifestyle 27. jun 2021 3 min Professor MSO Signe Sørensen Torekov Written by Morten Busch

Losing weight is difficult enough, but maintaining weight loss is almost impossible for many people. If you lose weight, your body increases your appetite and slows down your energy expenditure. Researchers have tested a combination therapy in which an exercise programme boosts energy expenditure and a medication suppresses appetite. This results not only in significant and lasting weight loss but, even more importantly, a healthier body with reduced fat percentage, increased fitness level and improved glucose regulation.

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Everyone who has tried to lose weight has noticed how well the human body can prevent this happening. If you lose weight, your hormonal system reacts abruptly, adjusting appetite hormones so that you feel very hungry. In addition, energy expenditure decreases and you burn fewer calories. Dieting therefore often results in the same outcome: losing weight for a while, but the extra kilos often pile back on in the long term. Now people with obesity have a beacon of hope.

“People have experienced promising weight loss, but this has proved difficult to maintain. We combined an exercise programme, to increase energy expenditure, with a medication to suppress appetite, and obtained additional weight loss and beneficial health effects for up to 1 year. We hope that maintaining these effects for 1 year and preferably longer can eventually alter the body’s hormone balance and by maintaining the exercise programme, creating lasting lifestyle changes,” explains Signe Sørensen Torekov, Professor with Special Responsibilities, Department of Biomedical Sciences, University of Copenhagen.

Lost twice as much fat

The trial participants were 195 people with obesity and a low fitness level. All the participants followed an 8-week low-calorie diet, which resulted in losing an average of 13 kg of body weight. In addition, as expected, the participants’ health improved significantly, primarily a decrease in blood glucose levels and blood pressure. Then the participants were divided into four groups.

“One carried out a moderate-to-vigorous exercise programme; one was treated with an appetite suppressant; a third group combined the appetite suppressant and the exercise programme; and the fourth group was a control group with habitual activity and placebo. The participants did not know whether they received the appetite suppressant or the placebo,” says Signe Sørensen Torekov.

The trial participants were monitored for 1 year to determine whether they regained the weight they had lost. Unsurprisingly, the people in the placebo group did, regaining 6 kg on average and, most importantly, the positive health effects that arose in the beginning disappeared. Both the exercise group and the appetite suppressant group maintained their weight loss during the trial period and reduced their body fat percentage.

“The people who both exercised and took the appetite suppressant lost another 3 kg but, even more importantly, they reduced their body fat percentage by 3.9 percentage points, about twice as much as both the exercise group and the appetite suppressant group. In addition, only the people carrying out the dual regimen had improved insulin sensitivity. Both exercise groups improved their fitness, which is an important health indicator associated with mortality from cardiovascular disease,” explains Signe Sørensen Torekov.

First time

The dual regimen of exercise and appetite suppressant thus provided twice as many health benefits as each individual regimen and resulted in a significant loss of fat mass and either maintaining or increasing muscle mass.

“Since increasing muscle mass provides significant health benefits, not focusing solely on weight but also on the physical distribution of fat and muscle mass is important. In addition, losing weight can trigger loss of muscle mass and less energy expenditure. Obesity treatment so far has typically focused on how to lose weight and not so much on how to maintain weight loss and the long-term health benefits,” says Signe Sørensen Torekov.

Half of Denmark’s population is overweight and almost 20% have obesity, and this can have major health effects. Although the proportion of people with overweight varies greatly between countries and continents, having obesity is definitely associated with an increased risk of premature death and comorbid conditions such as type 2 diabetes, cardiovascular disease, cancer and reduced fertility – and especially reduced quality of life.

“This is the first well-documented study of which treatment method is best for maintaining healthy weight loss. We show for the first time how people with obesity can maintain weight loss by comparing four strategies for maintaining weight loss – new knowledge that doctors, dietitians and physiotherapists can use in practice. This is the evidence we have been lacking,” explains Signe Sørensen Torekov.

Survival instinct for at least a full year

Thus, an exercise programme consisting of mostly vigorous-intensity exercise for about 2 hours a week combined with an appetite suppressant therefore seems to work. Obtaining the appetite suppressant, an analogue of the appetite suppressant peptide GLP-1, requires a prescription. The trial showed that the exercise programme often requires feedback from a healthcare professional.

“We continually ensured that the trial participants actually exercised and received help and support for this, because maintaining weight loss is hard work. The trial also showed very clearly that the people in the placebo group, who did not exercise, gained weight. Losing weight requires training and effort, probably for many years,” explains Signe Sørensen Torekov, who adds:

“People who lose weight struggle against powerful biological processes, and we have previously measured the hormone-induced increase in appetite following weight loss. We hope to better understand how, whether and when the appetite hormone balance can be normalized after weight loss while maintaining the exercise programme.”

Healthy weight loss maintenance with exercise, liraglutide, or both combined” has been published in The New England Journal of Medicine. In 2016, the Novo Nordisk Foundation awarded a grant to Signe Sørensen Torekov for the project Synergistic Effects of GLP-1 and Exercise on Immunometabolic Health.

Signe Sørensen Torekov, M.Sc. Human biology, PhD, is Professor MSO at the Department of Biomedical Sciences, University of Copenhagen, Denmark, and al...

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