Share
array:23 [ "pii" => "S2387020624004881" "issn" => "23870206" "doi" => "10.1016/j.medcle.2024.05.020" "estado" => "S200" "fechaPublicacion" => "2024-11-01" "aid" => "6723" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2024" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "edi" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:18 [ "pii" => "S0025775324003890" "issn" => "00257753" "doi" => "10.1016/j.medcli.2024.05.016" "estado" => "S200" "fechaPublicacion" => "2024-07-16" "aid" => "6723" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "edi" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "¿Ha cambiado el primer tratamiento de la diabetes mellitus tipo<span class="elsevierStyleHsp" style=""></span>2?" "tienePdf" => "es" "tieneTextoCompleto" => "es" "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Has the first treatment of type<span class="elsevierStyleHsp" style=""></span>2 diabetes mellitus changed?" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lilliam Flores, Josep Vidal" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Lilliam" "apellidos" => "Flores" ] 1 => array:2 [ "nombre" => "Josep" "apellidos" => "Vidal" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020624004881" "doi" => "10.1016/j.medcle.2024.05.020" "estado" => "S200" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624004881?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775324003890?idApp=UINPBA00004N" "url" => "/00257753/unassign/S0025775324003890/v1_202407160438/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2387020624005084" "issn" => "23870206" "doi" => "10.1016/j.medcle.2024.02.023" "estado" => "S200" "fechaPublicacion" => "2024-11-01" "aid" => "6632" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Image in medicine</span>" "titulo" => "Skeletal dysplasia" "tienePdf" => "en" "tieneTextoCompleto" => "en" "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Displasia esquelética" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1272 "Ancho" => 1500 "Tamanyo" => 212367 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alejandra Romano Medina, María José Bartolomé Albistegui, Margarita del Carmen Castro Rey, Andrea Patricia Espinoza Leiva" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Alejandra" "apellidos" => "Romano Medina" ] 1 => array:2 [ "nombre" => "María José" "apellidos" => "Bartolomé Albistegui" ] 2 => array:2 [ "nombre" => "Margarita del Carmen" "apellidos" => "Castro Rey" ] 3 => array:2 [ "nombre" => "Andrea Patricia" "apellidos" => "Espinoza Leiva" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775324002021" "doi" => "10.1016/j.medcli.2024.02.019" "estado" => "S200" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775324002021?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624005084?idApp=UINPBA00004N" "url" => "/23870206/unassign/S2387020624005084/v1_202411010428/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2387020624004637" "issn" => "23870206" "doi" => "10.1016/j.medcle.2024.04.030" "estado" => "S200" "fechaPublicacion" => "2024-10-21" "aid" => "6709" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Perineal leiomyoma: an infrecuent clinical entity" "tienePdf" => "en" "tieneTextoCompleto" => "en" "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Leiomioma perianal: una entidad poco frecuente" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1236 "Ancho" => 2050 "Tamanyo" => 374050 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Anal lesion: (A) Tumour measuring 4<span class="elsevierStyleHsp" style=""></span>cm in greatest diameter, pedunculated and located in the right posterolateral quadrant of the anus. (B) Image of the surgical specimen showing an oval lesion with well-defined margins. (C) Appearance of the anal region after surgical resection.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Pathological study: (D) Cross-linked fascicles of spindle cells with eosinophilic cytoplasm, nuclei with conical ends and small nucleoli, consistent with smooth muscle cells (H&E stain, 200×) are visible.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemistry study (E and F) showing strongly positive staining for actin (E) and negative for CD117, with positive mast cells as internal control, confirming the diagnosis of leiomyoma (F) (400×).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Raquel Ruiz-Fernández, Daniel Fernández-Martínez, Iván Fernández-Vega" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Raquel" "apellidos" => "Ruiz-Fernández" ] 1 => array:2 [ "nombre" => "Daniel" "apellidos" => "Fernández-Martínez" ] 2 => array:2 [ "nombre" => "Iván" "apellidos" => "Fernández-Vega" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775324003671" "doi" => "10.1016/j.medcli.2024.04.034" "estado" => "S200" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775324003671?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624004637?idApp=UINPBA00004N" "url" => "/23870206/unassign/S2387020624004637/v1_202410210424/en/main.assets" ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Has the first treatment of type 2 diabetes mellitus changed?" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Lilliam Flores, Josep Vidal" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Lilliam" "apellidos" => "Flores" "email" => array:1 [ 0 => "lflores@clinic.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Josep" "apellidos" => "Vidal" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Endocrinología y Nutrición, Unidad de Obesidad, Hospital Clínic, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Ha cambiado el primer tratamiento de la diabetes mellitus tipo 2?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The aetiology of type 2 diabetes mellitus (DM2) is complex and involves numerous pathophysiological deficits affecting multiple organs. Insulin resistance (IR) in the muscle and liver, as well as β-cell dysfunction, are the main abnormalities responsible for the development and progression of hyperglycaemia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In addition, IR is associated with other metabolic disorders, such as obesity, mainly visceral obesity, hypertension, dyslipidaemia, endothelial dysfunction, inflammation and a hypercoagulable state. Each of these factors, along with IR, has been associated with the development of atherosclerotic cardiovascular disease, which contributes to the increased risk of cardiovascular disease (CVD) in patients living with DM2.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">It is generally agreed that CVD is the leading cause of morbidity and mortality in DM2,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> so numerous studies have made efforts to reduce CVD through achieving better glycaemic control. However, meta-analyses that include these studies show a rather modest reduction in major cardiovascular (CV) events, with a greater benefit in non-fatal myocardial infarction, with no significant effect on stroke.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> On the other hand, STENO-2, which used a multifactorial approach but placed less emphasis on improving blood glucose and lowering haemoglobin A1c, showed a significant reduction in both CV events and CV mortality. Therefore, it appears that treatment that is simply focused on hyperglycaemia and not on the concomitant management of the other IR syndrome components is unlikely to produce a sustained decrease in hyperglycaemia and decrease the risk of developing CVD.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The ideal treatment for DM2 is one that is able to reverse or halt at least eight of the pathophysiological deficits described in the <span class="elsevierStyleItalic">Ominous Octet</span> in the year 2009, in which, in addition to IR in the muscle (decreased glucose uptake), liver (increased hepatic glucose production) and progressive insufficiency of insulin secretion by the pancreatic β-cells, a dysfunction of α-cells in the pancreas (increased glucagon secretion), IR of adipose tissue (increased lipolysis), decreased gastrointestinal incretin effect, increased renal reabsorption of glucose and dysfunction of neurotransmitters in the brain (decreased satiety) are added.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> This suggests that to prevent or delay progressive β-cell insufficiency, treatment should not simply be based on lowering A1c, but may require, along with lifestyle changes, an early combination of drugs to correct the multiple known pathophysiological deficits. In this sense, for about 5 years there has been a paradigm shift in the management of DM2, which recommends applying these modern concepts and guiding treatment according to the pathophysiology of the disease to achieve a benefit (reduction of CVD), as opposed to the classical approach of reaching a target (A1c level).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Over the last two decades, the vast majority of clinical guidelines have recommended metformin as first-line therapy in DM2 due to its efficacy, low cost and well-established safety profile, so the current debate focuses on whether we should replace this treatment in favour of the SGLT2 inhibitors (sodium–glucose 2 cotransporter inhibitors) and GLP-1 analogues (glucagon-like peptide 1 receptor agonists) which have recently demonstrated both CV safety and a reduction in major CV events (including heart failure and renal protection) in randomised clinical trials as part of the regulatory requirements for approval of new antidiabetic agents. To guide treatment decisions in this patient population, it would seem logical to have CV benefit studies with metformin and comparative studies between metformin and these new agents in both primary and secondary prevention.</p><p id="par0025" class="elsevierStylePara elsevierViewall">But what do we know about the CV benefits of metformin? Although metformin is an oral antidiabetic drug that has been widely used for many years as a first-line treatment for DM2, much of the evidence on CV outcomes comes from indirect comparative studies or sub-analyses of clinical trials designed to evaluate other antidiabetic treatments, as well as studies comparing metformin with classic antidiabetic drugs that are no longer in use, which limits the ability to extrapolate these results to routine clinical practice. The CV benefits of metformin were demonstrated in 1998 in the UK Prospective Diabetes Study (UKPDS) substudy, which included a small number of overweight patients with DM2 at low CV risk, but showed CV benefits mainly in myocardial infarction, diabetes-related death and all-cause mortality compared with conventional treatment.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In addition, when patients treated with metformin were compared to those treated with sulphonylureas or insulin, patients on metformin treatment showed less diabetes-related complications, lower overall mortality and a benefit in stroke.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">On the other hand, it should be noted that the trials of SGLT2 inhibitors<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–10</span></a> and GLP-1 analogues<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–14</span></a> that have shown safety and CV benefits (Cardiovascular Outcome Trials [CVOT]) were conducted in patients with DM2 at high CV risk, the majority of whom had established CVD (population other than the UKPDS) and were already receiving standard treatment, which generally included metformin (70%–80%), so that the benefits observed with these drugs were mostly in combination with metformin. To understand how these drugs interact with each other and whether they may have synergistic or antagonistic effects on CV outcomes, some CVOTs with these drugs have conducted post hoc analyses to investigate whether metformin modifies the observed protective effect, with conflicting results. In the <span class="elsevierStyleItalic">post-hoc</span> analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) study, in which 76% of patients were using metformin, it was observed that patients who were not using metformin at baseline experienced more pronounced CV benefits compared to those who were using metformin.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In contrast, the efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY) study, with 73% of patients on metformin treatment, showed a significant CV benefit of albiglutide in patients on metformin treatment at baseline.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Among the SGLT2 inhibitors, the hazard ratios in the Empagliflozin, Cardiovascular Outcomes, and Mortality in type 2 diabetes (EMPA-REG) and Canagliflozin and Cardiovascular and Renal Event in type 2 diabetes (CANVAS) studies suggested that the CV benefit observed was mainly due to the CV benefit obtained in patients who were not receiving metformin treatment at baseline.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,18</span></a> However, it is important to remember the limitations of <span class="elsevierStyleItalic">post hoc</span> analyses and that the results should be interpreted with caution. Regarding secondary prevention, given the current evidence and the ethical principles of beneficence and non-maleficence, it will not be possible to conduct trials comparing metformin with placebo in this group of patients. In primary prevention, a recent meta-analysis of 30 CVOTs (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>225,305) with GLP-1 analogues and SGLT2 inhibitors showed a reduction in the risk of major adverse cardiovascular events (MACE) that was consistent across CVD patients. (HR: 0.87; CI 95%: 0.83–0.92) and without CVD (HR: 0.92; CI 95%: 0.83–1.02).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> As regards metformin, there is only one ongoing active comparator trial to assess the superiority of dapagliflozin versus metformin as first-line treatment in patients with DM2<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>4 years in reducing CV events (Clinicaltrials.gov: NCT03982381), with an estimated completion date of October 2025. In summary, the evidence for metformin as a cardioprotective agent is less consistent and robust than that for SGLT2 inhibitors and GLP-1 analogues, but what impact have the CVOT results with GLP-1 analogues and SGLT2 inhibitors had on clinical guidelines?</p><p id="par0035" class="elsevierStylePara elsevierViewall">These studies have led to a process of continuous updating of clinical guidelines for the management of DM2. The consensus published in 2018 proposed by the American Diabetes Association (ADA) and the European Association for Study of Diabetes (EASD) laid the groundwork for a significant change in the approach to DM2 by highlighting the importance of CVD prevention and personalisation of treatment to improve clinical outcomes in patients. This approach has continued to evolve in subsequent recommendations from other medical organisations and societies, such as the European Society of Cardiology (ESC) and EASD in 2019 and the ESC in 2023, further reinforcing the paradigm shift in the management of DM2 towards a holistic, patient-centred approach.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The ADA 2024 recommendations for the management of DM2 consolidate the personalised approach and include guidelines stratified by CV risk. These guidelines recommend considering GLP-1 analogues and SGLT2 inhibitors as first-line treatments, regardless of glycaemic control, in patients with established CVD, heart failure and/or chronic kidney disease. In addition, ADA suggests that initial combination therapy should be considered in people with elevated A1c levels, and metformin, SGLT2 inhibitors or GLP-1 analogues are recommended as long-term first-line treatment for patients with DM2 and prior CV events, but without heart failure. As second-line treatment, DPP-4 inhibitors, pioglitazone, acarbose and insulin should be considered. In patients with DM2 who have had previous heart failure, SGLT-2 inhibitors are recommended as long-term first-line treatment. Finally, and for the first time, the ADA Standards of Care 2024 emphasise the importance of weight control as an integral part of DM2 management. The implications of the ADA 2024 recommendations for the use of metformin as first-line therapy in DM2 include a change in the approach to initiation to one that is personalised and tailored, taking into account individual patient characteristics and comorbidities.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Recognising the CV benefits of GLP-1 analogues and SGLT2 inhibitors has had a major impact on clinical practice in the management of DM2 and CVD in general, with a shift in treatment recommendations to prioritise consideration of these drugs in patients with established CVD or multiple CV risk factors, with a broader focus on primary and secondary prevention of major CV events and on reducing the risk of hospitalisation for heart failure, with a greater emphasis on the CV risk profile of patients when selecting drugs for the treatment of DM2, and an impact on multidisciplinary care with increased collaboration between diabetes specialists, cardiologists and other healthcare professionals in the comprehensive management of patients with DM2 and CVD.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In view of the above, it does not seem justifiable to continue to consider metformin as a universal first-line treatment for all patients with DM2.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">Both authors declare that they have no potential conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflict of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.A. DeFronzo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/db09-9028" "Revista" => array:6 [ "tituloSerie" => "Diabetes" "fecha" => "2009" "volumen" => "58" "paginaInicial" => "773" "paginaFinal" => "795" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19336687" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Insulin resistance: the link between obesity and cardiovascular disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.M. Reaven" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.mcna.2011.06.002" "Revista" => array:6 [ "tituloSerie" => "Med Clin North Am" "fecha" => "2011" "volumen" => "95" "paginaInicial" => "875" "paginaFinal" => "892" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21855697" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "The Emerging Risk Factors Collaboration" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)60484-9" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "375" "paginaInicial" => "2215" "paginaFinal" => "2222" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20609967" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of intensive glycemic control on cardiovascular outcomes and all-cause mortality in type 2 diabetes: overview and metaanalysis of five trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "I. Tkáč" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0168-8227(09)70011-7" "Revista" => array:6 [ "tituloSerie" => "Diabetes Res Clin Pract" "fecha" => "2009" "volumen" => "86" "paginaInicial" => "S57" "paginaFinal" => "S62" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20115934" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P. Gæde" 1 => "P. Vedel" 2 => "N. Larsen" 3 => "G.V.H. Jensen" 4 => "H.-H. Parving" 5 => "O. Pedersen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa021778" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2003" "volumen" => "348" "paginaInicial" => "383" "paginaFinal" => "393" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12556541" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Challenging 2019 ESC guidelines for the management of type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.J. Scheen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.diabet.2019.10.006" "Revista" => array:6 [ "tituloSerie" => "Diabetes Metab" "fecha" => "2020" "volumen" => "46" "paginaInicial" => "181" "paginaFinal" => "185" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31707046" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)" ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(98)07037-8" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1998" "volumen" => "352" "paginaInicial" => "854" "paginaFinal" => "865" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9742977" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Zinman" 1 => "C. Wanner" 2 => "J.M. Lachin" 3 => "D. Fitchett" 4 => "E. Bluhmki" 5 => "S. Hantel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1504720" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2015" "volumen" => "373" "paginaInicial" => "2117" "paginaFinal" => "2128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26378978" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The CANVAS program: implications of canagliflozin on reducing cardiovascular risk in patients with type 2 diabetes mellitus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Carbone" 1 => "D.L. Dixon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12933-019-0869-2" "Revista" => array:5 [ "tituloSerie" => "Cardiovasc Diabetol" "fecha" => "2019" "volumen" => "18" "paginaInicial" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31138195" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dapagliflozin and cardiovascular outcomes in type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.D. Wiviott" 1 => "I. Raz" 2 => "M.P. Bonaca" 3 => "O. Mosenzon" 4 => "E.T. Kato" 5 => "A. Cahn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1812389" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2019" "volumen" => "380" "paginaInicial" => "347" "paginaFinal" => "357" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30415602" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.C. Gerstein" 1 => "H.M. Colhoun" 2 => "G.R. Dagenais" 3 => "R. Diaz" 4 => "M. Lakshmanan" 5 => "P. Pais" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(19)31149-3" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2019" "volumen" => "394" "paginaInicial" => "121" "paginaFinal" => "130" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31189511" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Husain" 1 => "A.L. Birkenfeld" 2 => "M. Donsmark" 3 => "K. Dungan" 4 => "F.G. Eliaschewitz" 5 => "D.R. Franco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1901118" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2019" "volumen" => "381" "paginaInicial" => "841" "paginaFinal" => "851" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31185157" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.P. Marso" 1 => "S.C. Bain" 2 => "A. Consoli" 3 => "F.G. Eliaschewitz" 4 => "E. Jodar" 5 => "L.A. Leiter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1607141" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2016" "volumen" => "375" "paginaInicial" => "1834" "paginaFinal" => "1844" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27633186" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liraglutide and cardiovascular outcomes in type 2 diabetes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.P. Marso" 1 => "G.H. Daniels" 2 => "K. Brown-Frandsen" 3 => "P. Kristensen" 4 => "J.F.E. Mann" 5 => "M.A. Nauck" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1603827" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2016" "volumen" => "375" "paginaInicial" => "311" "paginaFinal" => "322" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27295427" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of liraglutide on cardiovascular outcomes in type 2 diabetes patients with and without baseline metformin use: post hoc analyses of the LEADER trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. Crowley" 1 => "D.K. McGuire" 2 => "A.-S. Alexopoulos" 3 => "T.J. Jensen" 4 => "S. Rasmussen" 5 => "H.A. Saevereid" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc20-0437" "Revista" => array:6 [ "tituloSerie" => "Diabetes Care" "fecha" => "2020" "volumen" => "43" "paginaInicial" => "e108" "paginaFinal" => "e110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32647053" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.F. Hernandez" 1 => "J.B. Green" 2 => "S. Janmohamed" 3 => "R.B. D’Agostino" 4 => "C.B. Granger" 5 => "N.P. Jones" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(18)32261-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2018" "volumen" => "392" "paginaInicial" => "1519" "paginaFinal" => "1529" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30291013" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "1112-P: does background T2D therapy modify the benefits of dapagliflozin in heart failure? Analysis of the DAPA-HF trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Docherty" 1 => "S.E. Inzucchi" 2 => "M.N. Kosiborod" 3 => "L. Kober" 4 => "A. Langkilde" 5 => "F. Martinez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/db20-1112-P" "Revista" => array:4 [ "tituloSerie" => "Diabetes" "fecha" => "2020" "volumen" => "69 Suppl 1" "paginaInicial" => "1112-P" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Are the cardiovascular and kidney benefits of empagliflozin influenced by baseline glucose-lowering therapy?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.E. Inzucchi" 1 => "D. Fitchett" 2 => "D. Jurišić-Eržen" 3 => "V. Woo" 4 => "S. Hantel" 5 => "C. Janista" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/dom.13938" "Revista" => array:6 [ "tituloSerie" => "Diabetes Obes Metab" "fecha" => "2020" "volumen" => "22" "paginaInicial" => "631" "paginaFinal" => "639" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31789445" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glucose-lowering drugs or strategies, atherosclerotic cardiovascular events, and heart failure in people with or at risk of type 2 diabetes: an updated systematic review and meta-analysis of randomised cardiovascular outcome trials" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O.R. Ghosh-Swaby" 1 => "S.G. Goodman" 2 => "L.A. Leiter" 3 => "A. Cheng" 4 => "K.A. Connelly" 5 => "D. Fitchett" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-8587(20)30038-3" "Revista" => array:6 [ "tituloSerie" => "Lancet Diabetes Endocrinol" "fecha" => "2020" "volumen" => "8" "paginaInicial" => "418" "paginaFinal" => "435" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32333878" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes—2024" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N.A. ElSayed" 1 => "G. Aleppo" 2 => "R.R. Bannuru" 3 => "D. Bruemmer" 4 => "B.S. Collins" 5 => "L. Ekhlaspour" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2337/dc24-S009" "Revista" => array:5 [ "tituloSerie" => "Diabetes Care" "fecha" => "2024" "volumen" => "47 Suppl 1" "paginaInicial" => "S158" "paginaFinal" => "S178" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/unassign/S2387020624004881/v1_202411010428/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/23870206/unassign/S2387020624004881/v1_202411010428/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624004881?idApp=UINPBA00004N" ]
