A long and stony road to the correct treatment of obesity

Lecube, Albert; Ciudin, Andreea

doi:10.1016/j.medcle.2021.06.003

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Who among us does not know a patient to whom another professional has made this or a similar comment? Well yes, obesity is not only an extremely prevalent disease, but also a highly mistreated one. Mistreated by health professionals, who often despise it and run away from it; mistreated by society, which blames the sufferer without any subtlety; mistreated by fortune, which until recently has not provided it with minimally effective and safe drugs.It is true, obesity is not easy to treat. In fact, more than 95% of patients suffering from it only receive nutritional and physical activity advice, if they are lucky. Are they useful? Of course. Demonstrated in reality show format in The biggest loser and in randomised clinical trials such as Look AHEAD.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a> Applicable to real life? Having a personal trainer, a nutritionist, the right environment and the ability to maintain all of this for the rest of our lives is hardly going to be possible. Because let us not forget, obesity is a chronic and relapsing disease. And what is worse, each time the patient loses weight, his/her basal metabolism is reduced.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> That is why we cannot hand out photocopied diets left, right and centre, insisting that patients start their umpteenth attempt to lose weight, if we are not going to be able to treat them properly. Our metabolic adaptability will make each attempt more difficult than the last. We seldom believe the patient, but he or she is often right. Therefore, let us refrain from prescribing a low-calorie diet if we will not be able to properly accompany the patient throughout his or her journey. If we continue to do so, it would be the same as telling a patient with bilateral lower limb oedema to drink less water and urinate more, without trying to find the cause and treat it properly.Although obesity is a cross-sectional disease, it is more prevalent in more socioeconomically disadvantaged classes.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> To make matters worse, drug therapy to combat obesity has never been funded by our health system. Currently, in Europe, we have 3 alternatives: orlistat (Xenical®), the combination of naltrexone and extended-release bupropion (Mysimba®) and liraglutide 3.0mg (Saxenda®): this means that the 3 have shown a difference compared to placebo of more than 5% of weight loss, or that at least 35% of the treated subjects have achieved a weight loss of more than 5% after one year of treatment, with twice as many responders as in the placebo group.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a>Orlistat, available since July 1998, is a pancreatic lipase inhibitor that achieves modest weight reductions after 12 months of treatment (95% credible interval [95% CrI] between −3.0 and −2.1kg compared to placebo), at the expense of decreasing stool consistency and increasing the risk of fat-soluble vitamin malabsorption. The second option, which combines an opioid agonist and an atypical antidepressant, has been available since March 2015 and fights obesity in a dependence-like way by reducing the desire for food and the eating-derived rewarding sensation. After one year of treatment, it achieves losses between 5.9 and 3.9kg (95% CrI), with the most common adverse reactions being nausea, constipation, headache, dry mouth, dizziness, and vomiting. The third, liraglutide 3.0mg, also available in Europe since March 2015, is a glucagon-like peptide-1 (GLP-1) receptor agonist that requires daily subcutaneous administration and is already experienced in clinical practice at lower doses (up to 1.8mg/day) in the treatment of type 2 diabetes mellitus. Weight losses after one year of treatment with 3.0mg liraglutide are −5.3kg (95% CrI, between −6, 06 and −4.52kg), with 63% of patients losing>5% of baseline weight.<a class="elsevierStyleCrossRefs" href="#bib0025">5,7</a> The main adverse reaction is nausea and vomiting in the first weeks of treatment.And that was the situation until March 2021 when the results of the randomised clinical trial with semaglutide were published, another GLP-1 receptor agonist, at a dose of 2, 4mg weekly in patients with a body mass index ≥30kg/m2 or ≥27kg/m2 if at least one obesity-related comorbidity coexisted.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> After 68 weeks of treatment, the group assigned to semaglutide lost 14.9% of their baseline weight, compared to only 2.4% in the placebo group. Translated to kilograms: –15.3kg with semaglutide and –2.6kg with placebo. In addition, 50.5% of patients treated with semaglutide lost 15% or more of their baseline weight, and, at the cost of how many adverse reactions? Nausea and diarrhoea were the most common, of mild to moderate intensity in most cases, forcing discontinuation of treatment in only 4.5% of participants.These results place us in a completely different scenario from the current one. The possibility that drugs with the capacity to modify the life course of obese patients will soon be available. Drugs that can achieve results similar to those of bariatric surgery. A type of surgery that only reaches 2% of all potential candidates, leaving many patients helpless, seeing their survival inevitably shortened and their quality of life greatly diminished due to obesity.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> And now for the last question: Can we remain idle in the face of the possibility that this new drug treatment option will likewise not be financed by the National Health System? The signatories of this editorial, the patients we treat on a daily basis and the scientific society we represent refuse to accept this possibility, this inequity, this injustice.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> We call for solutions that favour the progressive introduction of a universal treatment for obesity, accepting that it could initially be limited to the most severe cases, and encouraging agreements between the health authority and the pharmaceutical industry. Let us dare, let us take the STEP (<a href="http://www.demoselpaso">www.demoselpaso</a>), and let us keep declaring war on obesity. A war which, of course, cannot forget preventive measures aimed at the whole spectrum of the population.Conflict of interestsIn the last 5 years the authors have participated in advisory meetings and conferences promoted by Novo Nordisk Pharma. Albert Lecube has also received funding for research projects related to weight loss from Novo Nordisk Pharma and AstraZeneca." "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Lecube A, Ciudin A. Un largo y pedregoso camino hacia el correcto tratamiento de la obesidad. 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ISSN: 2387-0206

Launched in 1943, Medicina Clínica is a fortnightly journal aimed at the promotion of clinical research and practice among internal medicine and other specialists. The key characteristics of Medicina Clínica are the scientific and methodological rigor of its manuscripts, the topicality of its contents, and, especially, its practical focus with highly useful information for clinical practice. Medicina Clínica is predominantly interested in publishing original research manuscripts, which are rigorously selected according to their quality, originality, and interest, and also in continued medical education-oriented manuscripts, which are commissioned by the journal to relevant authors (Editorials, Reviews, and Diagnosis and Treatment). These manuscripts contain updated topics with a major clinical or conceptual relevance in modern medicine. The journal adheres to the standards of academic research publications in all aspects including peer-review and ethical principles. Medicina Clínica is included in the General and Internal Medicine category of Thomson Reuters.

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