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Drug makes weight loss easier for people with genetic obesity

An already-available medication may help people with a certain type of genetically caused obesity lose weight and keep it off.

Around two to six percent of all people with obesity develop it in early childhood; it’s in their genetic cards. Mutations in one of their “appetite genes” gives them a strong genetic predisposition for developing obesity, also called monogenic obesity. Their experience of hunger is overruling and their feeling of satiety limited.

In addition, this group of people doesn’t respond to existing treatments the way others do. Diets and surgery can help people in this group lose weight, but many are unable to maintain the weight loss.

New research may offer another option. In a study in the journal Cell Metabolism, researchers have discovered that this group can lose weight with the help of liraglutide, a modified form of the appetite-inhibiting hormone GLP-1 naturally secreted from the intestine when we eat.

“These people develop obesity because they are genetically programmed to do so. That is, they are struggling with what is probably the strongest human drive: the desire to eat and thus to survive,” says study lead Signe Sørensen Torekov, associate professor from the biomedical sciences department at the University of Copenhagen and the Novo Nordisk Foundation Center for Basic Metabolic Research. “However, the appetite-inhibiting drug liraglutide has a positive effect on them. They feel less hungry and lose six percent of their body weight within four months.”

In this study, the researchers examined 14 people with obesity caused by pathogenic mutations in the so-called MC4R gene and 28 persons with obesity without the mutations. They treated both groups with the medicine for four months; no changes were made to their diet and level of exercise in this period.

The individuals with this most common form of monogenic obesity lost 7 kg (15.4 pounds) of their body weight compared to 6 kg (13.2 pounds) for the people with the common form.

“We are positively surprised to see that the treatment has a good effect on this group of people. Many researchers have believed that the function of the medicine was mainly to inhibit the appetite by stimulating this specific appetite receptor in the brain which does not work in this particular group of people with obesity. However, our study shows that the medicine still has an appetite-inhibiting effect and thus must affect the appetite in a different way,” says Torekov.

Medicine acting as an analogue to our natural GLP-1 hormone is already available, and has been FDA and EMA licensed for the treatment of obesity and type 2 diabetes. The new study indicates it could be a possible treatment for the most common form of genetically caused obesity, where patients respond poorly to existing treatments.

“People who have suffered from obesity all their lives probably are not aware that it is caused by this mutation. It can therefore be a huge relief for many to learn why they have developed obesity and that there is actually a treatment that works,” says first author Eva Winning Iepsen.

Gene variants may make obesity ‘all but inevitable’

She also points out that the medicine makes it easier for people with this monogenic form of obesity to control their blood sugar. The medicine can, therefore, also have an effect on diabetes and pre-diabetes often seen in this particular group of individuals with genetically determined obesity.

As MC4R mutations cause obesity in early childhood, the researchers hope the results can pave the way for new studies on young people in the future. If they are able to prevent this condition before young people reach adulthood, it will have a great positive effect on their health and perhaps also social stigmatization, the researchers believe.

The study is a case-control study conducted in a smaller group of people. Thus it has more statistical weight than studies in animals and cell cultures but less than larger randomized trials in humans.

The Danish Diabetes Academy, the Novo Nordisk Foundation, the Lundbeck Foundation, the Region Zealand Health Sciences Research Foundation, and Aase and Ejnar Danielsen’s Foundation funded the study. Signe Sørensen Torekov holds stock in Novo Nordisk A/S.

Source: University of Copenhagen

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