What Are the Current and Future Challenges in Obesity?

Carla Nieto Martínez

December 30, 2022

MADRID — Not only are strategies for managing obesity changing, but also the "absolute truths" and guidelines for obesity are being reassessed, especially with reference to how clinicians advise patients on managing the problem and how they involve patients in treatment. These ideas were presented in two sessions at the 63rd Conference of the Spanish Society of Endocrinology and Nutrition (Sociedad Española de Endocrinología y Nutrición).

The closing conference was titled, "The Future in the Treatment of Obesity: A Perspective for the 21st Century," and was led by Carel Le Roux, MBChB, PhD, director of the Metabolic Medicine Group of the University College Dublin in Ireland.

"Many of the certainties that we currently know about obesity are going to change in the next few years, and within this framework, the main question that we need to answer is whether it is a disease," said Le Roux. "Most experts believe that it is, but that does not mean that in practice it is approached as such. We must not forget that there are around 220 complications associated with obesity, not only metabolic but also of another type, which must be treated."

Le Roux added, "The definition of obesity of the World Health Organization is the abnormal excess of adipose tissue that leads to a deterioration in health. It is terrible, but it is the best definition that we have today. However, when managing this concept, we must be capable of identifying two distinct entities: on the one hand, the evidence that obesity is a disease; on the other, the cultural desire to be thin.

"The latter, in principle, is not a poor premise, as long as the importance of clearly transmitting to the patient the message that he or she is being treated for a disease is not lost, underscoring that the main objective is not to make them thin only for them to be happier or to look better physically. We have to overcome the idea that our work is to help people lose weight, assuming instead that the obligation of endocrinologists is to treat a disease. As a result of doing so, the patient will lose weight naturally," he added.

Rethinking BMI

"When we treat obesity, we have to question many of the principles that we have always taken to be true," said Le Roux. "One of these is the role played by BMI [body mass index]. Without a doubt, it is an incredible epidemiological variant, and it has been a very useful tool in the past, although I do not believe it will be so in the future. But I believe that it is not a diagnosis in itself, nor is it an infallible parameter. In my opinion, we must consider it as a screening test. So, if someone comes to the consultation with a BMI of 30, the first thing to do is a diagnosis to confirm whether that person suffers from obesity, since there are patients that have a low BMI and they continue to exhibit the disease."

Le Roux underscored that another principle the specialist must reconsider is that of reducing energy intake and increasing energy expenditure. "We must consider obesity as a thermostat dysfunction, and in this sense, it is important to note its pathognomonic symptoms. Furthermore, we now know that it is a neurological disease or, better yet, neuroendocrine. Therefore, the cerebral mechanisms implicated must also be considered (concretely, the sensations of hunger and satiety), since obesity has genetic determinants, and 80% of the genes associated with it are found in the CNS."

During the session, "Obesity Treatment: Key Points in the Present and Future," Javier Salvador Rodríguez, MD, director of the Department of Endocrinology and Nutrition at the Navarra University Clinic in Spain, and Ignacio Llorente, MD, medical subdirector at the Nuestra Señora de Candelaria University Hospital in Santa Cruz de Tenerife, Spain, analyzed future challenges in the approach to obesity.

The experts debated the implications for the endocrinologist of considering obesity to be a chronic disease. For Llorente, this premise implies following up patients, independently of the results obtained, and taking notice that, owing to this chronicity (ie, long duration, slow evolution, and difficult cure or remission), it is necessary for patients to be attended by health services. Doing so ensures their coverage and provides them with the necessary resources. "We as endocrinologists must believe that obesity is a chronic disease and be the protagonists of its management, as we do with other pathologies," said Llorente.

Salvador emphasized the need to prevent and mitigate the stigmatization of people with obesity. "The studies conducted about this demonstrate that the stigma is absolutely devastating for the personality of the patient, it breaks them down and leads to marginalization. It also favors chronification of the disease and leads to an increase in the complications. It is clear that stigmatization originates from weight bias (which suggests to the patient that obesity is his or her own fault). It is rooted in the lack of understanding of the problem, the existence of a wide range of genetic alterations that are associated with obesity. Luckily, there are more therapeutic resources for this."

Stigma, Therapeutic Failure

"It is true that modifications in lifestyle are key for the treatment of obesity, but they are not the only factors implicated in its genesis. Therefore, if we focus only on the attitude of the patient and their will to be successful in the treatment, we are wrong, because if they fail in their attempt, we stigmatize them," added Llorente.

According to both specialists, the evidence leaves no room for doubt that the stigma associated with obesity increases complications and makes them more chronic. Thus, the educational role and the conviction of the healthcare professional is fundamental.

Advances in pharmacologic treatment translate into a better probability for individualization and therapeutic success. But there are two aspects to consider: precocity and duration over time.

"The main advantage arising from an early start of comprehensive treatment of obesity is fundamental to reduce the probability of developing an associated comorbidity. In this sense, there is a very important concept: multimorbidity, which is either simple (associated with another two major diseases) or complex (four associated diseases)," said Llorente.

"It has been shown that the fact of having obesity is associated with a threefold higher comorbidity than in the population without this disease. However, simple multimorbidity is multiplied by five in grade 3 obesity, while in complex obesity, it is 12 times more than in the healthy population. Therefore, the fact of having obesity is going to determine that in a moment of life (around 55 years of age), the patient will have the same multiple comorbidities as a person who is 75 years old without the disease. So, therein lies the importance of taking care with tendencies and movements, such as 'metabolically healthy obesity' or 'health in any size,' because they are incorrect. A patient who is obese and not treated will develop comorbidities," the specialist added.

Salvador underscored the clear relationship between the duration of obesity and the development of comorbidities, as occurs with other chronic diseases. "Investigations in this sense have demonstrated that the average time that passes between when a patient begins to worry about his or her weight and a consultation with his or her physician is 6 years. Thus, therapeutic intervention must be done quickly to avoid falling into therapeutic inertia once weight loss is attained."

With regard to the duration of pharmacologic treatment of obesity, Llorente referred to the recommendations published in the Canadian Medical Association Journal. The therapeutic approach must be maintained over time with the aim of avoiding weight gain. "The pharmacological treatment of obesity shows a clear efficacy that is lost when it is discontinued. It calls for its chronic administration in a vast majority of cases.

"We as specialists continue to consider that all obesities are the same, and that is not true," said Salvador. "We need more studies to know what the best strategy in each case is, and the arrival of new, more potent drugs cannot cloud our vision nor make us forget the evidence that a comprehensive treatment is always necessary."

New Drugs

Speakers also discussed what can be expected from new, second-generation drugs. The main benefit will be a greater percentage of weight loss with maximum long-term safety. Some drugs can be used soon. Others have recently been approved by the US Food and Drug Administration. In 2021, semaglutide was approved as a pharmacologic treatment for the long-term control of weight. In October 2022, approval was quickly granted for tirzepatide as a drug to treat obesity. All these drugs are undergoing phase 3 clinical development for obesity. The drugs' effects on weight loss and in the adolescent population are being explored. Cardiovascular safety also will be evaluated. A crucial question is whether these therapeutic options help patients lose weight safely, which the current drugs have not done.

Salvador disagreed with this point. In his opinion, the guarantee of long-term safety has still not been achieved. "I believe that the advantages of the new drugs, more than with regard to safety, will be a lower rate of nonresponders in terms of weight loss. These molecules are also going to allow us to treat comorbidities (ie, hepatic steatosis) in a way that we never thought possible with a pharmacological treatment. Therefore, the message is this: let us use the pharmacological treatments according to the summary of product characteristics."

The session, "Obesity Treatment: Key Points in the Present and Future," was sponsored by Novo Nordisk. Llorente and Salvador have disclosed no relevant financial relationships. Le Roux works for various pharmaceutical and nutrition companies.

Follow Carla Nieto of Medscape Spanish Edition on Twitter @carlanmartinez and on LinkedIn.

This article was translated from the Medscape Spanish edition.


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