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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Obesity is a common comorbidity in chronic inflammatory conditions such as psoriasis &#40;PsO&#41; and hidradenitis suppurativa &#40;HS&#41;&#44; in which the common underlying pathogenic mechanisms are closely related to those found in obesity&#46; It will be interesting to see whether the new and effective therapeutic alternatives under development for obesity enable a more effective decrease in body weight&#44; which&#44; in turn&#44; could be beneficial for the outcome of immune-mediated dermatoses&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Low-grade chronic inflammation and immunological imbalance facilitate a bidirectional association between obesity and immune-mediated dermatoses</span><p id="par0010" class="elsevierStylePara elsevierViewall">An excess of dysfunctional adiposity contributes to the inflammatory state that characterizes patients with obesity&#46;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">1&#8211;4</span></a> As low-grade inflammation underlies obesity&#44; PsO&#44; and HS &#40;<a class="elsevierStyleCrossRef" href="#sec0130">Fig&#46; S1 of additional material</a>&#41;&#44; any intervention that dampens the mechanisms that lead to this state will be positive for any of the 3 conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">5&#44;6</span></a> The mechanisms that underlie the bidirectional association between obesity and immune-mediated diseases<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">7</span></a> have not been clearly established&#44; although it is accepted that the skin plays a causative role in chronic inflammation and immune disorders &#40;<a class="elsevierStyleCrossRef" href="#sec0130">Fig&#46; S2 additional material</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0470"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The incidence of PsO and HS has increased in western countries in recent decades&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">9&#44;10</span></a> Obesity has increased in parallel&#44; and could be responsible&#44; at least partially&#44; for the aforementioned increase&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">8</span></a></p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Psoriasis and obesity</span><p id="par0020" class="elsevierStylePara elsevierViewall">The prevalence of obesity is higher among patients with PsO than in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">11&#8211;18</span></a> In addition&#44; obesity increases the risk of PsO&#44;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">6&#44;19&#44;20</span></a> the incidence of which could be twice as great in patients with grade II&#47;III obesity compared with subjects with normal weight&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">21</span></a> Among the molecular mediators at the intersection between the 2 conditions are 3 adipokines&#8212;leptin&#44; resistin&#44; and adiponectin&#8212;whose levels impact the severity of PsO in patients with obesity&#46;<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">22&#8211;24</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Many complications associated with obesity are also associated with PsO&#46; There is a higher prevalence of type 2 diabetes mellitus &#40;DT2&#41; in patients with PsO than in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">25</span></a> In addition&#44; insulin resistance induces dyslipidemia and contributes to the development of nonalcoholic hepatic steatosis &#40;NAHS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">26</span></a> Cardiovascular risk &#40;CVR&#41; is increased in patients with obesity and PsO who present psoriatic arthritis&#44; and who often have other risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">27</span></a> The guidelines for the European Cardiology Society state that the body mass index &#40;BMI&#41; should not exceed 25<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">28</span></a> and so early interventions to manage obesity or excess weight associated with PsO could contribute to preventing CVR&#46; Finally&#44; obesity is associated with worse response to drugs for PsO &#40;<a class="elsevierStyleCrossRef" href="#sec0130">Table S1 additional material</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">29&#44;30</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Hidradenitis suppurativa and obesity</span><p id="par0030" class="elsevierStylePara elsevierViewall">There is a higher prevalence of obesity in subjects with HS than in the general population&#44;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">31&#44;32</span></a> and HS is detected more frequently in children with obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">33</span></a> The association between HS and obesity&#44; as is the case for PsO&#44; is also bidirectional&#44; with low-grade inflammation as the unifying thread&#46; Inflammatory imbalance in obesity perpetuates inflammation and follicular occlusion&#46; Multiple molecular mechanisms&#44; activated by inflammatory mediators&#44; contribute to the progression of HS&#46;<a class="elsevierStyleCrossRefs" href="#bib0605"><span class="elsevierStyleSup">34&#44;35</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The prevalence of DT2 is higher in subjects with HS than in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">36</span></a> HS is also associated with other conditions traditionally linked with obesity&#44; such as metabolic syndrome&#44; polycystic ovarian syndrome&#44; and inflammatory bowel disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0620"><span class="elsevierStyleSup">37&#8211;39</span></a> and patients with HS are exposed to higher CVR than the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">40</span></a> Obesity negatively impacts the response of patients to the main treatments for HS &#40;<a class="elsevierStyleCrossRef" href="#sec0130">Table S1 additional information</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">15</span></a></p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Advantages associated with weight loss in patients with obesity and psoriasis or hidradenitis suppurativa</span><p id="par0040" class="elsevierStylePara elsevierViewall">In addition to better response to treatments for inflammatory dermatoses&#44; other arguments justify the desirability of patients with obesity and PsO or HS to lose weight&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Weight loss is associated with a decrease in PsO severity and improved quality of life &#40;QoL&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0640"><span class="elsevierStyleSup">41&#44;42</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Weight loss greater than 5&#37; is associated with a higher rate of minimum disease activity in patients who are obese or overweight and in treatment for PsO&#46;<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">43&#44;44</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">The Mediterranean diet&#44; which facilitates weight loss&#44; reduces psoriatic lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">45</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Weight loss in patients with HS leads to a notable decrease in the number of lesions and&#44; in some cases&#44; disease remission&#46;<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">46</span></a></p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Dysfunctional adiposity has been associated with worse indices of CVR and Dermatology Quality of Life Index &#40;DLQI&#41; in patients with HS&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">47</span></a></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">The decrease in fatty tissue is associated with a decrease in molecular mechanisms that characterize the systemic inflammatory state&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">48</span></a></p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Specific treatments for weight loss</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Diet and exercise</span><p id="par0075" class="elsevierStylePara elsevierViewall">Diet and exercise are the first therapeutic step but these interventions are&#44; however&#44; often insufficient to achieve favorable outcomes in skin diseases&#44; good response to treatment for these conditions&#44; and a decrease in CVR&#46; Another limitation is the poor adherence and high drop-out rates&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">49</span></a> Therefore&#44; pharmacological options should also be explored&#46; The limited number of treatments able to significantly reduce weight&#44; as well as the risk of renewed weight gain from 6 months after the end of intervention&#44; have been an obstacle for considering pharmacological treatment for obesity in patients with PsO or HS&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Approved and marketed drugs in Spain</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Orlistat</span><p id="par0080" class="elsevierStylePara elsevierViewall">Orlistat is an inhibitor of the gastric and pancreatic lipases that block hydrolysis of triacyl glycerides and absorption of fatty acids through the intestinal endothelium&#46; The drug is often associated with gastrointestinal adverse events&#44; thereby hindering adherence&#46; Its effect is modest&#44; with weight losses of not more than 3&#37; after 12 months&#44; after which time&#44; the weight is partially regained&#44; even with continuing therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">50</span></a> There are no studies that have analyzed the effect of orlistat in patients with obesity and PsO or HS&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">GLP-1 receptor agonists</span><p id="par0085" class="elsevierStylePara elsevierViewall">GLP-1 receptor agonists have recently made a mark as a possible pharmacological alternative for weight loss&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Indications&#44; pleiotropic actions</span><p id="par0090" class="elsevierStylePara elsevierViewall">GLP-1 receptor agonists are analogs of GLP-1&#44; an intestinal peptide hormone of &#8764;3&#46;3 kDa belonging to the incretin family&#46; On binding to the GLP-1 cell receptor&#44; these agents trigger the same molecular mechanisms as those induced by the endogenous peptide&#46; The interaction occurs in different tissues &#40;pancreas&#44; brain&#44; myocardium&#44; endothelium&#44; kidney&#44; digestive system&#41;&#44; which means that its actions&#44; including glycemic control with minimum risk of hypoglycemia&#44; have a pleiotropic character &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">51</span></a> Moreover&#44; a series of clinical trials suggest that the GLP-1 receptor agonists could induce cardiovascular protection&#46;<a class="elsevierStyleCrossRefs" href="#bib0695"><span class="elsevierStyleSup">52&#8211;55</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">GLP-1 receptor agonists in the obesity setting</span><p id="par0095" class="elsevierStylePara elsevierViewall">The GLP-1 receptor agonists currently on the market have a molecule weight &#40;MW&#41; less than 5 kDa &#40;except for dulaglutide&#41;&#44; and a circulating half-life greater than the 5<span class="elsevierStyleHsp" style=""></span>minutes of the native GLP-1 molecule&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">56</span></a> Brain nuclei such as the paraventricular nucleus of the thalamus and arcuate nucleus express GLP-1 receptors&#44; although it is the former that appears to play the most important part in control of food intake&#46;<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">57&#44;58</span></a> The GLP-1 receptor agonists for treatment of obesity in the European Union &#40;EU&#41;&#44; liraglutide &#40;3<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; subcutaneous&#41; and semaglutide &#40;2&#46;4<span class="elsevierStyleHsp" style=""></span>mg in a weekly subcutaneous dose&#41;&#44; are &#62;<span class="elsevierStyleHsp" style=""></span>90&#37; homologous with the structure of human GLP-1&#46; Liraglutide has a half-life of 13<span class="elsevierStyleHsp" style=""></span>h&#44; and reaches brain tissue on crossing the blood brain barrier&#46; It is debated whether this action occurs by passive diffusion or&#44; in contrast&#44; requires interaction with the GLP-1 receptor&#46;<a class="elsevierStyleCrossRefs" href="#bib0730"><span class="elsevierStyleSup">59&#8211;70</span></a> The semaglutide molecule has a longer aliphatic chain&#44; conferring greater hydrophobicity&#46; The incorporation of polyethylene glycol not only modifies its hydrolysis target by dipeptidyl peptidase-4&#44; but also increases its affinity for albumin&#46; These characteristics prolong its circulating half-life to up to 165<span class="elsevierStyleHsp" style=""></span>h&#44; and&#44; when conjugated with albumin&#44; the molecule is able to penetrate the spinal chord&#44; septal nucleus&#44; and hypothalamus via the circumventricular organs&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">60</span></a> Once in the satiety centers&#44; liraglutide and semaglutide act on the neuronal populations of the pro-opiomelanocortin and NPY&#47;AgRP neurons&#44; implicated in metabolic activity&#44; and&#44; through as yet little known mechanisms&#44; are able to reduce the hunger sensation&#46; This action makes these agents a therapeutic option for weight loss&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">56</span></a> Although to a lesser extent&#44; delay in gastric emptying contributes to the anorexigenic effect&#46;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">61</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Clinical trials conducted with GLP-1 receptor agonists in patients with obesity &#40;or excess weight &#91;BMI &#8805; 27&#93; with comorbidities&#41;&#44; or with DT2 and excess weight or obesity&#44; have achieved weight reductions greater than those reported for orlistat&#44; as well as those observed with oral antidiabetic agents such as the sodium glucose type 2 cotransporter inhibitors &#40;SGLT2i&#41; or metformin&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">62</span></a> In a meta-analysis of more than 10 000 patients with obesity&#44; those treated with GLP-1 receptor agonists lost&#44; on average&#44; 7<span class="elsevierStyleHsp" style=""></span>kg more than those in the control group&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">63</span></a> Weight loss of up to 15&#37; has been observed after 12 months of treatment&#44;<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">64&#44;65</span></a> a level that had only been achieved through surgical methods&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dosing&#44; safety profile</span><p id="par0105" class="elsevierStylePara elsevierViewall">GLP-1 receptor antagonists with an indication for obesity &#40;or excess weight &#91;BMI &#8805; 27<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#93; with complications&#41; are administered subcutaneously every week or daily&#46; The use of GLP-1 receptor agonists is frequently associated with gastrointestinal adverse effects&#44; particularly nausea&#44; vomiting&#44; diarrhea or constipation&#59; these are transient and of mild to moderate intensity&#46; Their onset can be avoided or the severity reduced to a large extent if dose escalation is performed as indicated in the label&#44; and if&#44; while treatment lasts&#44; a series of well-defined dietary and behavioral recommendations are followed&#46;<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">66</span></a> In patients who observe these recommendations&#44; the adverse effects may disappear in a few days or weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">67</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Arguments in favor of GLP-1 receptor agonists for weight control in patients with obesity and inflammatory dermatoses</span><p id="par0110" class="elsevierStylePara elsevierViewall">As mentioned earlier&#44; weight loss has a positive effect on the outcome and response to treatments for PsO and HS&#46; It is plausible to speculate that GLP-1 receptor agonists can induce greater weight loss than those obtained with other therapeutic interventions&#46; This can also improve adherence&#46; Furthermore&#44; GLP-1 receptor agonists induce anti-inflammatory effects that could attenuate the low-grade inflammation that underlies obesity&#44; PsO&#44; and HS &#40;reviewed recently in the context of PsO and psoriatic arthritis&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">68</span></a> Finally&#44; improved metabolic control and cardio-renal protection could be beneficial for reducing CVR and managing comorbidities such as DT2 or metabolic syndrome&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">GLP-1 receptor agonists with indication for obesity</span><p id="par0115" class="elsevierStylePara elsevierViewall">As mentioned earlier&#44; there are 2 GLT-1 receptor agonists indicated for the treatment of obesity in the EU in subjects with BMI &#8805; 30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> or BMI &#8805; 27<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> and at least one weight-related comorbidity&#44; always in combination with appropriate diet and physical exercise&#58; liraglutide 3<span class="elsevierStyleHsp" style=""></span>mg and semaglutide 2&#46;4&#160;mg&#46; The second&#44; although approved by European Medicines Agency &#40;EMA&#41; and the Spanish Agency for Medicines and Health Products &#40;AEMPS&#41;&#44; is still not marketed in Spain&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Liraglutide 3<span class="elsevierStyleHsp" style=""></span>mg</span><p id="par0120" class="elsevierStylePara elsevierViewall">This agent is administered subcutaneously every day&#46; The SCALE clinical trials were designed to assess the effectiveness and safety of this agent for weight loss in patients with obesity or overweight &#40;BMI &#8805; 27<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; with comorbidities&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the most relevant findings&#46; In a cohort of 3731 patients&#44; weight loss of 5&#37;&#44; 10&#37;&#44; and 15&#37; was observed in 63&#37;&#44; 33&#37;&#44; and 14&#37;&#44; respectively&#44; after 56 weeks of treatment &#40;27&#37;&#44; 11&#37;&#44; and 4&#37; with placebo&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">69</span></a> or of an additional 6&#37; at 56 weeks in patients who had already lost 6&#37; through hypocaloric diet and exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">70</span></a> Positive results were also observed in adolescent patients with obesity&#44;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">71</span></a> and in real-life studies substantial weight loss has also been reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0795"><span class="elsevierStyleSup">72&#8211;75</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg</span><p id="par0125" class="elsevierStylePara elsevierViewall">In the STEP trials &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; designed to evaluate the efficacy and safety of semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg &#40;subcutaneous&#44; weekly&#41; in patients with obesity&#44; or excess weight &#40;BMI &#8805; 27<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; with complications&#44; weight loss of between 15&#37; and 17&#37; was achieved 68 weeks after starting treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0815"><span class="elsevierStyleSup">76&#8211;78</span></a> In one of the trials&#44; weight loss of 10&#37; was reported after 20 weeks of therapy&#46; The subjects who&#44; at that time&#44; switched from semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg to placebo had regained half of that weight after 48 weeks&#44; whereas those who continued on active treatment achieved an additional weight loss of around 8&#37; in the same time period&#46; After 68 weeks with semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#44; losses of 5&#37;&#44; 10&#37;&#44; and 15&#37; were reported in 88&#37;&#44; 79&#37;&#44; and 63&#37; of patients&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">76</span></a> A recent meta-analysis concluded that semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg and liraglutide 3<span class="elsevierStyleHsp" style=""></span>mg are more efficacious than naltrexone-bupropion &#40;not marketed in Spain&#41; and orlistat&#46;<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">79</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Experience with liraglutide and semaglutide in psoriasis and hidradenitis suppurativa</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Liraglutide and psoriasis</span><p id="par0130" class="elsevierStylePara elsevierViewall">In studies with liraglutide&#44; patients with PsO and obesity had a diagnosis of DT2&#46; and so the doses did not exceed 1&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#44; which is the indicated dose for such patients&#46; Although the series had limited sample sizes&#44; the findings are interesting&#46; In a cohort of 7 patients with DT2 and obesity&#44; daily use of liraglutide 1&#46;2<span class="elsevierStyleHsp" style=""></span>mg achieved&#44; after 10 weeks&#44; a weight reduction of 5&#37; and a decrease in BMI of 2<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">80</span></a> In another study&#44; 3 patients with DT2 and obesity achieved a decrease in BMI of between 0&#46;8 and 3&#46;8<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> after 18 weeks with this same dose of liraglutide&#46;<a class="elsevierStyleCrossRef" href="#bib0840"><span class="elsevierStyleSup">81</span></a> Another 2 patients with obesity and DT2 achieved weight losses of more than 5<span class="elsevierStyleHsp" style=""></span>kg and a decrease in BMI of 1&#46;5 and 2<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> after 6 weeks of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">82</span></a> Finally&#44; in a series of 20 subjects with obesity and DT2&#44; an average weight loss of 4&#46;7<span class="elsevierStyleHsp" style=""></span>kg was reported after 8 weeks of treatment with liraglutide 1&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#46;<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">83</span></a> In most of these patients&#44; improvements in the psoriasis area severity index &#40;PASI&#41; was observed&#44; and on occasions&#44; a decrease in psoriatic plaques&#46; This observation could encourage investigation into whether this treatment is able to induce additional benefit&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Semaglutide and psoriasis</span><p id="par0135" class="elsevierStylePara elsevierViewall">Experience in this case is limited&#44; and no studies have been performed with the 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg dose&#46; There is a case report of a 73-year-old man with PsO&#44; obesity&#44; and DT2 who achieved a decrease in BMI from 40&#46;3 to 38&#46;3<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> after 10 months treatment with 1<span class="elsevierStyleHsp" style=""></span>mg weekly of semaglutide&#46;<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">84</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Liraglutide and hidradenitis suppurativa</span><p id="par0140" class="elsevierStylePara elsevierViewall">Experience with this agent is limited in HS&#46; There is a case report of a patient aged 19 years with HS and grade 2 obesity who started combination therapy with liraglutide 1&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#44; metformin&#44; levonorgestrel&#47;ethinylestradiol&#44; dapsone&#44; and finasteride&#46; She lost 16<span class="elsevierStyleHsp" style=""></span>kg in the first 6 months&#44; although she then progressively regained weight&#46;<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">85</span></a> There have been no reports of treatment of obesity with semaglutide in patients with HS&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Possibilities for use of GLP-1 receptor agonists in Spain for treatment of obesity</span><p id="par0145" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> shows a schematic overview of the treatment options which are currently available for weight control in Spain and which are applicable to patients who also have PsO or HS&#46; The doses of liraglutide or semaglutide are different depending on whether the patient has DT2&#44; is overweight &#40;BMI &#8805; 27<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; with comorbidities or has obesity &#40;with or without DT2&#41;&#46; In addition&#44; in patients with DT2&#44; there is the possibility of using an oral presentation of semaglutide&#46; The effects of this presentation on weight and glycemia in clinical trials and real-world settings are comparable to those induced by the subcutaneous presentation&#44; although a specific indication for weight control without DT2 is still lacking&#46;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">86</span></a> In order to avoid confusion in daily clinical practice&#44; it is important to note that liraglutide 3<span class="elsevierStyleHsp" style=""></span>mg and semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg can be used in patients with DT2&#44; provided these are obese or overweight with comorbidities&#46; Patients with DT2 without obesity or excess weight with comorbidities can use liraglutide 1&#46;8<span class="elsevierStyleHsp" style=""></span>mg &#40;daily&#44; subcutaneous&#41; and semaglutide 1<span class="elsevierStyleHsp" style=""></span>mg &#40;weekly&#44; subcutaneous&#41;&#44; or 14<span class="elsevierStyleHsp" style=""></span>mg &#40;daily&#44; oral&#41; for glycemic control&#46; However&#44; they should not be treated with liraglutide 3<span class="elsevierStyleHsp" style=""></span>mg or semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#44; because these doses are not indicated for this condition&#46; The underlying reason is that&#44; in the case of parenteral presentations&#44; the effective doses of GLT-1 receptor agonists necessary for weight control are greater than those needed for glycemic control&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Other medium-term therapeutic options</span><p id="par0150" class="elsevierStylePara elsevierViewall">Tirzepatide&#44; still not approved in the EU for specific use in patients with obesity&#44; is a dual agonist of the GLP-1 receptors and another incretin&#44; gastric inhibitor polypeptide &#40;GIP&#41;&#46; In a phase 3 trial in subjects with obesity or overweight &#40;BMI &#8805; 27<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#44; its use for 18 months achieved weight loss of up to 20&#46;9&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">87</span></a></p></span></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0155" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Low-grade inflammation underlies obesity and PsO&#47;HS&#44; and this inflammation has a negative impact on both conditions&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Weight loss is beneficial for PsO and HS outcomes&#44; through a reduction in the inflammatory component of CVR&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0170" class="elsevierStylePara elsevierViewall">GLP-1 receptor agonists&#44; by achieving greater weight loss than obtained with other medications&#44; may represent a therapeutic opportunity for improving obesity in patients with PsO and HS&#44; with resulting decrease in CVR and&#44; in general&#44; improvement in the medium to long term&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0175" class="elsevierStylePara elsevierViewall">The formation of multidisciplinary teams comprised of dermatologists and endocrinologists may contribute to better management of patients with obesity&#47;overweight and immune-mediated dermatosis&#46;</p></li></ul></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0180" class="elsevierStylePara elsevierViewall">Laboratorios Novonordisk collaborated through funding for Medical Writing Services&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicts of Interest</span><p id="par0185" class="elsevierStylePara elsevierViewall">Eva Vilarrasa has received fees for consulting and&#47;or as a speader and&#47;or for travel and&#47;or has participated in clinical trials sponsored by Abbvie&#44; Almirall&#44; Amgen&#44; Boehringer Ingelheim&#44; Bristol-Meyers Squibb&#44; Celgene&#44; Gebro&#44; Isdin&#44; Janssen&#44; LEO Pharma&#44; Lilly&#44; Merck Serono&#44; MSD&#44; Novartis&#44; Pfizer&#44; Roche&#44; Sandoz&#44; Sanofi&#44; and UCB&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Joana Nicolau has received fees for presentations and consulting on behalf of Sanofi&#44; Novo Nordisk&#44; Lilly&#44; Boehringer-Ingelheim&#44; Fresenius&#44; AstraZeneca&#44; Fresenius&#44; Dexcom&#44; Amgen&#44; and Senseonics&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Pablo de la Cueva has participated as consultant and&#47;or investigator and&#47;or speaker for the following pharmaceutical companies&#58; Abbvie&#44; Almirall&#44; BMS&#44; Boehringer-Ingelheim&#44; Celgene&#44; Janssen Cilag&#44; LEO Pharma&#44; Lilly&#44; MSD&#44; Novartis&#44; Novo Nordisk&#44; Pfizer&#44; Roche&#44; Sanofi&#44; and UCB&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Albert Goday has received fees for investigation projects&#44; consulting&#44; and postgraduate training&#44; and has participated in clinical trials sponsored by Almirall&#44; Ascensia&#44; Colegio de Farmac&#233;uticos de Barcelona&#44; Esteve&#44; Federaci&#243;n Farmac&#233;utica&#44; Fundaci&#243;n Catalana S&#237;ndrome de Down&#44; Fundaci&#243; Gol i Gorina&#44; Instituto de Salud Carlos III&#44; Jansen&#44; Lilly&#44; Menarini&#44; MSD&#44; Mutuam&#44; Novo Nordisk&#44; Pronokal&#44; RedGDPS&#44; Rovi&#44; Sanofi Aventis&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Fernando Gallardo has received fees as presenter&#44; consultant&#44; and support for attendance of course and congresses and&#47;or investigation projects in the following companies&#58; Janssen&#44; Abbvie&#44; UCB&#44; Amgen&#44; Bristol&#44; Lilly&#44; Novartis&#44; Almirall&#44; Leo Pharma&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Antonio Martorell has received fees and&#47;or travel grants and&#47;or acted as a member of the steering committees from Novartis&#44; Abbvie&#44; Janssen Cilag&#44; UCB&#44; Lilly&#44; LEO Pharma&#44; L&#8217;Oreal&#44; Sanofi&#44; Boehringer Ingelheim&#44; Almirall&#44; Bristol Myers Squibb&#44; and Amgen&#46; He has also worked as the principal investigator in clinical trials sponsored by Abbvie&#44; UCB&#44; Janssen&#44; Bristol Myers Squibb&#44; Lilly&#44; Galderma&#44; Sanofi&#44; and Novartis&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Jos&#233; Manuel Carrascosa has participated as PI&#47;SI and&#47;or guest presenter and&#47;or advisor for Almirall&#44; Janssen&#44; Abbvie&#44; UCB&#44; Boehringer-Ingelheim&#44; Lilly&#44; Novartis&#44; Amgen&#44; BMS&#44; and Sandoz&#46;</p></span></span>"
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          "titulo" => "Low-grade chronic inflammation and immunological imbalance facilitate a bidirectional association between obesity and immune-mediated dermatoses"
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            0 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "Psoriasis and obesity"
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              "titulo" => "Hidradenitis suppurativa and obesity"
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          "titulo" => "Advantages associated with weight loss in patients with obesity and psoriasis or hidradenitis suppurativa"
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          "identificador" => "sec0025"
          "titulo" => "Specific treatments for weight loss"
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              "titulo" => "Approved and marketed drugs in Spain"
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                0 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Orlistat"
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                  "titulo" => "GLP-1 receptor agonists"
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                  "titulo" => "Indications&#44; pleiotropic actions"
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                3 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "GLP-1 receptor agonists in the obesity setting"
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                4 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "Dosing&#44; safety profile"
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                  "identificador" => "sec0065"
                  "titulo" => "Arguments in favor of GLP-1 receptor agonists for weight control in patients with obesity and inflammatory dermatoses"
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                  "identificador" => "sec0070"
                  "titulo" => "GLP-1 receptor agonists with indication for obesity"
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                  "identificador" => "sec0075"
                  "titulo" => "Liraglutide 3 mg"
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                8 => array:2 [
                  "identificador" => "sec0080"
                  "titulo" => "Semaglutide 2&#46;4 mg"
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                  "titulo" => "Experience with liraglutide and semaglutide in psoriasis and hidradenitis suppurativa"
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                    0 => array:2 [
                      "identificador" => "sec0090"
                      "titulo" => "Liraglutide and psoriasis"
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                  "identificador" => "sec0095"
                  "titulo" => "Semaglutide and psoriasis"
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                  "identificador" => "sec0100"
                  "titulo" => "Liraglutide and hidradenitis suppurativa"
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                12 => array:2 [
                  "identificador" => "sec0105"
                  "titulo" => "Possibilities for use of GLP-1 receptor agonists in Spain for treatment of obesity"
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                  "identificador" => "sec0110"
                  "titulo" => "Other medium-term therapeutic options"
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          "identificador" => "sec0115"
          "titulo" => "Conclusions"
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          "titulo" => "Funding"
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          "titulo" => "Conflicts of Interest"
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          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-05-11"
    "fechaAceptado" => "2023-06-28"
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          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Psoriasis"
            1 => "Hidradenitis suppurativa"
            2 => "Obesity"
            3 => "Glucagon-like peptide-1 &#40;GLP-1&#41; agonists"
            4 => "Liraglutide"
            5 => "Semaglutide"
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            0 => "Psoriasis"
            1 => "Hidradenitis supurativa"
            2 => "Obesidad"
            3 => "Agonistas del receptor de GLP-1"
            4 => "Liraglutida"
            5 => "Semaglutida"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Psoriasis and hidradenitis suppurativa are often associated with obesity&#46; Because chronic low-grade inflammation underlies these 2 diseases&#44; they can progress to more severe forms in patients with obesity if weight-reduction measures are not taken&#46; This review covers pharmacologic alternatives for treating obesity&#44; with emphasis on the benefits associated with the novel use of glucagon-like peptide-1 &#40;GLP-1&#41; agonists that act on satiety receptors&#46; These drugs have led to greater weight loss in clinical trials and real-world settings than orlistat&#44; which until recently was the only drug approved for treating obesity in the European Union&#46; Although experience with GLP-1 agonists in patients with obesity and inflammatory skin diseases is currently scarce&#44; the promising results reported suggest they may offer a useful tool for managing obesity&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La psoriasis &#40;PsO&#41; y la hidradenitis supurativa &#40;HS&#41; se asocian frecuentemente con la obesidad&#46; La inflamaci&#243;n cr&#243;nica de bajo grado subyace a estas condiciones&#44; por lo que si no se adoptan medidas para reducir el peso del paciente con obesidad y PsO o HS&#44; estas podr&#237;an evolucionar hacia formas m&#225;s graves&#46; Este trabajo revisa las opciones farmacol&#243;gicas para tratar la obesidad&#44; profundizando en los beneficios asociados al uso novedoso de agonistas del receptor de GLP-1 &#40;arGLP-1&#41;&#44; que act&#250;an sobre los centros de la saciedad&#46; Los resultados de ensayos y vida real demuestran que esta medicaci&#243;n consigue mayores p&#233;rdidas de peso que orlistat&#44; hasta recientemente el &#250;nico f&#225;rmaco espec&#237;fico para la obesidad comercializado en la Uni&#243;n Europea&#46; Aunque la experiencia con arGLP-1 en pacientes con obesidad y dermatosis inflamatorias es escasa&#44; los resultados son alentadores&#44; por lo que podr&#237;an constituir una herramienta &#250;til para el manejo de su obesidad&#46;</p></span>"
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            "etiqueta" => "Appendix B"
            "titulo" => "Additional material"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Pleiotropic effect of GLP-1 receptor agonists&#46; The effects of GLP-1 receptor agonists on different organs and&#44; in red&#44; their consequences&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">&#42;Glucose-dependent biosynthesis and secretion&#46; &#8224;Glucose-dependent secretion&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AMI&#58; acute myocardial infarction&#59; BP&#58; blood pressure&#59; CVA&#58; cerebrovascular accident&#59; FA fatty acids&#59; GLP-1 ra glucagon-like protein-1 receptor agonist&#59; IR&#58; insulin resistance&#46;</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Decision tree for use of GLP-1 receptor agonists indicated for weight control in patients with obesity or excess weight with comorbidities&#46; Different possibilities are considered depending on whether the patient is obese &#40;BMI&#8805; 30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; or overweight &#40;BMI&#8805; 27- &#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41; with &#8805; 1 weight-related comorbidity&#46; These therapeutic options can be used for weight control in patients with immune-mediated dermatosis who meet the above criteria&#46; Semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#44; although approved by the EMA and AEMPS&#44; has still not been marketed in Spain&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">&#42; At least 1 weight-related comorbidity&#58; in the case of liraglutide 3<span class="elsevierStyleHsp" style=""></span>mg&#44; poor glycemic control &#40;prediabetes or DT2&#41;&#44; hypertension&#44; dyslipidemia or sleep obstructive apnea&#59; in the case of semaglutide 2&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#44; glucose disorder &#40;prediabetes or DT2&#41;&#44; hypertension&#44; dyslipidemia&#44; sleep obstructive apnea&#44; or cardiovascular disease&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#8224; 3<span class="elsevierStyleHsp" style=""></span>mg&#44; daily&#44; subcutaneous administration&#44; in monotherapy or in combination with other medications&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#8225; 1&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#44; daily&#44; subcutaneous administration&#44; in monotherapy or in combination with other medications&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AEMPS&#58; Spanish Agency for Drugs and Medicinal Products&#59; BMI&#58; body mass index&#59; DT2&#58; type 2 diabetes&#59; EMA&#58; European Medicines Agency&#59; GLP-1&#58; glucagon-like peptide 1 receptor&#59; HS&#58; hidradenitis suppurativa&#59; MET&#58; metformin&#59; PsO&#58; psoriasis&#46;</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AEs&#44; adverse events&#59; BMI&#44; body mass index at baseline&#59; Pl&#58; placebo&#59; SID&#44; once daily&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liraglutide 3 mg vs&#46; Pl &#40;2&#58;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liraglutide 3 mg vs&#46; Pl &#40;1&#58;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg vs&#46; Pl &#40;2&#58;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg vs&#46; Pl &#40;2&#58;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg vs&#46; Pl &#40;2&#58;1&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Design&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomized&#47;double blind&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Run-in&#58; diet &#43;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">exercise</span>&#8226; <span class="elsevierStyleItalic">Week 0-56&#58;</span> randomized&#47;double blind&#44; liraglutide 3 mg or Pl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomized&#47;double blind&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Randomized&#47;double blind&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Week 0-20 &#40;run-in&#41;</span>&#58;semaglutide&#8226; <span class="elsevierStyleItalic">Week 20-68&#161;</span>&#58; randomized&#47;doubleblind&#44; semaglutide or Pl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients &#40;n&#59; BMI<span class="elsevierStyleSup">b</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3731&#59; 38&#46;3 kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">422&#59; 37&#46;8 kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1961&#59; 37&#46;9 kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">611&#59; 38&#46;0 kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">803&#59; 38&#46;4 kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Therapeutic regimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liraglutide 3 mg SID vs&#46; Pl &#40;plus lifestyle intervention&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Run-in&#58;</span> low calory diet &#43;<span class="elsevierStyleHsp" style=""></span>exercise&#8226; <span class="elsevierStyleItalic">Week 0-56&#58;</span> liraglutide 3 mg SID vs&#46; Pl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg&#47;week vs&#46; Pl &#40;plus lifestyle intervention&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg&#47;week vs&#46; Pl &#40;&#43; lifestyle intervention &#43;<span class="elsevierStyleHsp" style=""></span>low-calory diet in weeks 1-8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Week 0-20&#58;</span> semaglutide 2&#46;4 mg&#47;week&#8226; <span class="elsevierStyleItalic">Week 21-68&#58;</span> semaglutide 2&#46;4 mg&#47;week vs&#46; Pl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Weight loss&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liraglutide 3 mg&#58; -8&#46;0&#37;&#44; Pl&#58; 2&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Run-in&#58;</span>Liraglutide 3 mg&#58; -5&#46;9&#37;&#44;Pl -6&#37;&#8226; <span class="elsevierStyleItalic">From randomization until 56 weeks later&#58;</span>Liraglutide 3 mg&#58; -6&#46;2&#37;&#44;Pl -0&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg&#58; -14&#46;9&#37;&#44; Pl&#58; -2&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg&#58; -16&#46;0&#37;&#44;Pl&#58; -5&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Week 0-68&#58;</span> semaglutide 2&#46;4 mg&#58;-17&#46;4&#37;&#44; Pl&#58; -5&#46;0&#37;&#8226; <span class="elsevierStyleItalic">Week 20-68&#58;</span> semaglutide 2&#46;4 mg&#58;-7&#46;9&#37;&#44; Pl&#58; &#43;<span class="elsevierStyleHsp" style=""></span>6&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Discontinuation due to AEs<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#8225;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liraglutide 3 mg&#58; 9&#46;9&#37;&#44;Pl&#58; 3&#46;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Liraglutide 3 mg&#58; 8&#46;5&#37;&#44; Pl&#58; 8&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg&#58; 7&#46;0&#37;&#44; Pl&#58; 3&#46;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Semaglutide 2&#46;4 mg&#58; 5&#46;9&#37;&#44; Pl&#58; 2&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8226; <span class="elsevierStyleItalic">Week 0-20&#58;</span> semaglutide 2&#46;4 mg&#58; 5&#46;3&#37;&#8226; <span class="elsevierStyleItalic">Week 20-68&#58;</span> semaglutide 2&#46;4 mg&#58; 2&#46;4&#37;&#44; Pl&#58; 2&#46;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                    0 => array:2 [
                      "titulo" => "Revisiting the adipocyte&#58; a model for integration of cytokine signaling in the regulation of energy metabolism"
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                        0 => array:2 [
                          "etal" => false
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                    0 => array:2 [
                      "doi" => "10.1152/ajpendo.00297.2015"
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                        "tituloSerie" => "Am J Physiol Endocrinol Metab&#46;"
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                        "volumen" => "309"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inflammation in obesity&#44; diabetes&#44; and related disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                    0 => array:2 [
                      "doi" => "10.1016/j.immuni.2021.12.013"
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                        "tituloSerie" => "Immunity&#46;"
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                        "volumen" => "55"
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                        "link" => array:1 [
                          0 => array:2 [ …2]
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              "etiqueta" => "3"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Class II major histocompatibility complex plays an essential role in obesity-induced adipose inflammation"
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cmet.2013.02.009"
                      "Revista" => array:6 [
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              "etiqueta" => "4"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes"
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                    0 => array:1 [
                      "Revista" => array:4 [
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                        "volumen" => "10"
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                  ]
                ]
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skin changes in the obese patient"
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                    0 => array:2 [
                      "doi" => "10.1016/j.jaad.2018.12.070"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Acad Dermatol&#46;"
                        "fecha" => "2019"
                        "volumen" => "81"
                        "paginaInicial" => "1037"
                        "paginaFinal" => "1057"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exploring the Links between Obesity and Psoriasis&#58; A Comprehensive Review"
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