The new drugs for treating obesity

Our brains create many illusions, and our sense of freedom may be one such illusion. But, says neuroscientist Ignacio Morgado, it’s an illusion that helps us live better lives. “Freedom includes a sense of responsibility, which generates social cohesion and promotes cooperation among people,” said Morgado. It’s a useful illusion that can also victimize some people. Some of the most visible victims are overweight people, who now make up 53.6% of Spain’s population. Yet many people, including doctors, think overweight people have a character flaw that prevents them from getting off the sofa and doing some exercise for better health.

This perspective on obesity as a lifestyle choice and not as a disease, has meant that “there never has been any investment in [anti-obesity] drugs in Spain,” according to Cristóbal Morales, an endocrinologist at the Virgin of Macarena Hospital (Hospital Virgen Macarena) in Seville (Spain), and a member of the Spanish Obesity Society (Sociedad Española de Obesidad - SEEDO). Nevertheless, the relationship between excess weight and diabetes, some types of cancer, and cardiovascular disease is well known, and some drugs to help very obese people lose weight have already been developed.

Diabetes drugs such as liraglutide and semaglutide administered at higher doses have proven to be effective for weight loss. A clinical trial published in the New England Journal of Medicine in 2021 showed that semaglutide resulted in an average weight loss of 15% in a group of nearly 2,000 patients, and a third of the study group lost more than 20% of their weight. The drug has been such a success in the United States that its manufacturer, Novo Nordisk, quickly ran out of supply shortly after its use for obesity was approved. The Spanish national health system will cover the cost of liraglutide and semaglutide when used to treat diabetes, but not for obesity.

These drugs mimic incretins, the hormones produced by our body when we eat. “They are analogs that are artificially modified to last longer in the body,” said Guadalupe Sabio, who researches the biological causes of diseases such as obesity at the National Center for Cardiovascular Research (CNIC) in Madrid. They also stimulate insulin production by the pancreas and reduce blood glucose levels, which makes them useful for treating diabetes. As they regulate what happens in the body when food is ingested, these drugs “also reduce appetite, prolong satiety [the feeling of fullness], and increase the basal metabolic rate [the amount of energy consumed by a body at rest], thereby increasing thermogenesis [the process of producing body heat],” said Sabio.

“Once the efficacy of this type of drug is widely recognized,” said Morales, “many pharmaceutical companies will develop and test their own products, and overall supply will increase.” The latest drug of this type approved in the US for treating diabetes is tirzepatide, manufactured by Eli Lilly and Company, which will also seek approval for its use in treating obesity. “It’s so powerful that half of the patients using it practically go into remission from diabetes,” said Morales. Administered at higher doses, Lilly’s product has proven to be surprisingly effective at battling obesity. A recent study published in the New England Journal of Medicine, found that it resulted in an average weight loss of 22.5%, which can amount to 55 pounds in some patients.

The success of these drugs makes some experts ask whether they can match the results of weight-loss procedures such as bariatric surgery and intragastric balloon placement. “I don’t think these drugs will supplant surgery altogether, but they can an alternative treatment for some overweight conditions,” said Carolina Perdomo, an endocrinology and nutrition specialist at the Navarra University Hospital in Pamplona (Spain). “Some people need to lose weight before having surgery, so these drugs can serve as a bridge therapy leading up to the surgical procedure,” she said.

Rubén Nogueiras, a researcher at the University of Santiago de Compostela (Spain), thinks that these drugs could be used to treat obesity continuously, in the same way they are used to treat diabetes. “Obesity is a chronic disease, so one would expect the drug therapy to be chronic as well.” This raises the question of possible side effects from long-term use, but Nogueiras does not consider this likely. “The most common side effect is nausea during the first two weeks of treatment, but most patients handle the drug well after that. So far, no major side effects from long-term use have been found during the extensive clinical trials that have been conducted,” said Nogueiras. “These [drugs] are compounds that stimulate normal pathways in our body, so the side effects are minimal. If a semaglutide slows down digestion and makes food remain in the stomach longer, some digestive discomfort may occur, but nothing more,” said Guadalupe Sabio.

Dieting disappointments

Significant numbers of people diet regularly (around 20% of the Spanish population, according to some surveys), and fail to main those diets at the same rate (around 80% according to SEEDO). Anti-obesity drugs could become an instant commercial success if not for their high price, which could cost hundreds of dollars per month. If not covered by private health insurance plans or national health systems, the cost could be an insurmountable obstacle for most people. However, experts caution that these drugs are indicated for people who have been diagnosed with chronic obesity, and are not meant for those who just want to slim down a bit to look good at the beach. In the study that tested tirzepatide to treat obesity, the average weight of the participants was 230 pounds, and their average body mass index (BMI) was 38 [weight divided by height in meters squared. An individual with a BMI above 25 is considered to be overweight. A BMI above 30 indicates obesity]. In some countries like Brazil, says Cristóbal Morales, “drugs sales for weight loss are enormous.” He warns against “trivializing obesity and treating it like an aesthetic problem when comprehensive lifestyle interventions are needed.”

Obesity begins in the mother’s womb and becomes entrenched through habits developed during early childhood. It is further aggravated by the large supply of unhealthy foods available in supermarkets and sedentary lifestyles brought on by social and technological changes. Fernando Fernández Aranda, head of research at the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona (Spain), and also head of the eating disorders unit at Bellvitge University Hospital, specializes in the psychological aspects of eating disorders. He believes that this type of drug can be “used to complement healthy habits, exercise, and psychological support, but is not a magic solution.” Fernández says obesity is a complex issue, and “for individuals, especially women, who have suffered significant neglect or emotional stress during childhood or adolescence, it can affect their eating behavior.”

Azucena García Palacios, a psychology professor at the Jaume I University in Castellón (Spain) and a member of the Spanish Biomedical Research Center in Physiopathology of Obesity and Nutrition says that “losing weight is not hard – keeping it off is the hard part.” People fitted with intragastric balloons sometimes fail to maintain their weight loss, which could also happen with pharmacological treatments. García says that these drugs “should not be sold as panaceas. Systematic studies have shown that people with previous psychological problems have a much lower success rate after an intragastric balloon placement.” She says that “obese people have more mental health problems,” and psychological treatment is a form of support for people who need to lose weight due to a medical problem. For it to work, the individual circumstances of each patient must be assessed. “When we want people to exercise, we know that if the activity is not linked to something meaningful for the patient, it’s difficult to sustain the exercise routine over time, so we work to create that link,” said García. “To treat binge eating, we have to look at the emotions that lead to binge eating. It could be a sense of rejection or maybe it’s just a habit. But the binge eating might be associated with a diagnosable problem, such as major depressive disorder. We have to see the look at the individual’s vulnerabilities and see where they lead so we can decide how we are going to act in each case,” she said.

The surprisingly positive results of the new anti-obesity drugs are, according to the experts, good news for people with serious health problems caused by excess weight. But before they can be treated with these drugs, private health insurance companies and national health systems must first acknowledge that obesity is a disease. This has already happened in the United Kingdom. The next step would be for the cost of these drugs to be covered by health insurance and national health systems. But for the time being, anyone wanting to lose a few pounds to fit into a wedding dress shouldn’t think about this type of solution. Nevertheless, the popularity of cosmetic procedures such as liposuction leaves little doubt that some people will want these drugs for a quick fix. But there are so many people who are overweight or obese, there is little chance of finding a solution without a global strategy. This strategy must address every aspect of the problem, from thoroughly understanding the condition’s most basic mechanisms, to challenging the social and economic aspects of a way of life that leads to an ever-increasing number of people vulnerable to one of the major diseases of the modern world.