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Editorial article
A long and stony road to the correct treatment of obesity
Un largo y pedregoso camino hacia el correcto tratamiento de la obesidad
Albert Lecubea,b,
Corresponding author
alecube@gmail.com

Corresponding author.
, Andreea Ciudinb,c
a Servicio de Endocrinología y Nutrición, Hospital Universitari Arnau de Vilanova de Lleida, Obesity, Diabetes and Metabolism Research Unit, Institut de Recerca Biomèdica de Lleida (IRBLleida), Universitat de Lleida, Lérida, Spain
b Sociedad Española para el Estudio de la Obesidad (SEEDO), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
c Servicio de Endocrinología y Nutrición, Hospital Universitari Vall d’Hebron de Barcelona, Diabetes and Metabolism Research Unit, Institut de Recerca Vall d’Hebron (VHIR), Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">&#8220;Don&#8217;t come back until you lose 20<span class="elsevierStyleHsp" style=""></span>kilos&#8221;&#46; Who among us does not know a patient to whom another professional has made this or a similar comment&#63; Well yes&#44; obesity is not only an extremely prevalent disease&#44; but also a highly mistreated one&#46; Mistreated by health professionals&#44; who often despise it and run away from it&#59; mistreated by society&#44; which blames the sufferer without any subtlety&#59; mistreated by fortune&#44; which until recently has not provided it with minimally effective and safe drugs&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">It is true&#44; obesity is not easy to treat&#46; In fact&#44; more than 95&#37; of patients suffering from it only receive nutritional and physical activity advice&#44; if they are lucky&#46; Are they useful&#63; Of course&#46; Demonstrated in <span class="elsevierStyleItalic">reality show</span> format in <span class="elsevierStyleItalic">The biggest loser</span> and in randomised clinical trials such as Look AHEAD&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Applicable to real life&#63; Having a personal trainer&#44; a nutritionist&#44; the right environment and the ability to maintain all of this for the rest of our lives is hardly going to be possible&#46; Because let us not forget&#44; obesity is a chronic and relapsing disease&#46; And what is worse&#44; each time the patient loses weight&#44; his&#47;her basal metabolism is reduced&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> That is why we cannot hand out photocopied diets left&#44; right and centre&#44; insisting that patients start their umpteenth attempt to lose weight&#44; if we are not going to be able to treat them properly&#46; Our metabolic adaptability will make each attempt more difficult than the last&#46; We seldom believe the patient&#44; but he or she is often right&#46; Therefore&#44; 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&#46; If we continue to do so&#44; it would be the same as telling a patient with bilateral lower limb oedema to drink less water and urinate more&#44; without trying to find the cause and treat it properly&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Although obesity is a cross-sectional disease&#44; it is more prevalent in more socioeconomically disadvantaged classes&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> To make matters worse&#44; drug therapy to combat obesity has never been funded by our health system&#46; Currently&#44; in Europe&#44; we have 3 alternatives&#58; orlistat &#40;Xenical&#174;&#41;&#44; the combination of naltrexone and extended-release bupropion &#40;Mysimba&#174;&#41; and liraglutide 3&#46;0<span class="elsevierStyleHsp" style=""></span>mg &#40;Saxenda&#174;&#41;&#58; this means that the 3 have shown a difference compared to placebo of more than 5&#37; of weight loss&#44; or that at least 35&#37; of the treated subjects have achieved a weight loss of more than 5&#37; after one year of treatment&#44; with twice as many responders as in the placebo group&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Orlistat&#44; available since July 1998&#44; is a pancreatic lipase inhibitor that achieves modest weight reductions after 12 months of treatment &#40;95&#37; credible interval &#91;95&#37; CrI&#93; between &#8722;3&#46;0 and &#8722;2&#46;1<span class="elsevierStyleHsp" style=""></span>kg compared to placebo&#41;&#44; at the expense of decreasing stool consistency and increasing the risk of fat-soluble vitamin malabsorption&#46; The second option&#44; which combines an opioid agonist and an atypical antidepressant&#44; 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&#46; After one year of treatment&#44; it achieves losses between 5&#46;9 and 3&#46;9<span class="elsevierStyleHsp" style=""></span>kg &#40;95&#37; CrI&#41;&#44; with the most common adverse reactions being nausea&#44; constipation&#44; headache&#44; dry mouth&#44; dizziness&#44; and vomiting&#46; The third&#44; liraglutide 3&#46;0<span class="elsevierStyleHsp" style=""></span>mg&#44; also available in Europe since March 2015&#44; is a glucagon-like peptide-1 &#40;GLP-1&#41; receptor agonist that requires daily subcutaneous administration and is already experienced in clinical practice at lower doses &#40;up to 1&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; in the treatment of type 2 diabetes mellitus&#46; Weight losses after one year of treatment with 3&#46;0<span class="elsevierStyleHsp" style=""></span>mg liraglutide are &#8722;5&#46;3<span class="elsevierStyleHsp" style=""></span>kg &#40;95&#37; CrI&#44; between &#8722;6&#44; 06 and &#8722;4&#46;52<span class="elsevierStyleHsp" style=""></span>kg&#41;&#44; with 63&#37; of patients losing<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>5&#37; of baseline weight&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;7</span></a> The main adverse reaction is nausea and vomiting in the first weeks of treatment&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">And that was the situation until March 2021 when the results of the randomised clinical trial with semaglutide were published&#44; another GLP-1 receptor agonist&#44; at a dose of 2&#44; 4<span class="elsevierStyleHsp" style=""></span>mg weekly in patients with a body mass index &#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> or &#8805;<span class="elsevierStyleHsp" style=""></span>27<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> if at least one obesity-related comorbidity coexisted&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> After 68 weeks of treatment&#44; the group assigned to semaglutide lost 14&#46;9&#37; of their baseline weight&#44; compared to only 2&#46;4&#37; in the placebo group&#46; Translated to kilograms&#58; &#8211;15&#46;3<span class="elsevierStyleHsp" style=""></span>kg with semaglutide and &#8211;2&#46;6<span class="elsevierStyleHsp" style=""></span>kg with placebo&#46; In addition&#44; 50&#46;5&#37; of patients treated with semaglutide lost 15&#37; or more of their baseline weight&#44; and&#44; at the cost of how many adverse reactions&#63; Nausea and diarrhoea were the most common&#44; of mild to moderate intensity in most cases&#44; forcing discontinuation of treatment in only 4&#46;5&#37; of participants&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">These results place us in a completely different scenario from the current one&#46; The possibility that drugs with the capacity to modify the life course of obese patients will soon be available&#46; Drugs that can achieve results similar to those of bariatric surgery&#46; A type of surgery that only reaches 2&#37; of all potential candidates&#44; leaving many patients helpless&#44; seeing their survival inevitably shortened and their quality of life greatly diminished due to obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> And now for the last question&#58; 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&#63; The signatories of this editorial&#44; the patients we treat on a daily basis and the scientific society we represent refuse to accept this possibility&#44; this inequity&#44; this injustice&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> We call for solutions that favour the progressive introduction of a universal treatment for obesity&#44; accepting that it could initially be limited to the most severe cases&#44; and encouraging agreements between the health authority and the pharmaceutical industry&#46; Let us dare&#44; let us take the STEP &#40;<a href="http://www.demoselpaso">www&#46;demoselpaso</a>&#41;&#44; and let us keep declaring war on obesity&#46; A war which&#44; of course&#44; cannot forget preventive measures aimed at the whole spectrum of the population&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">In the last 5 years the authors have participated in advisory meetings and conferences promoted by Novo Nordisk Pharma&#46; Albert Lecube has also received funding for research projects related to weight loss from <span class="elsevierStyleGrantSponsor" id="gs0005">Novo Nordisk</span> Pharma and <span class="elsevierStyleGrantSponsor" id="gs0010">AstraZeneca</span>&#46;</p></span></span>"
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