Scientific letter
Potential of insulin deprescription adding a GLP-1 receptor agonist as a therapeutic strategy to improve the metabolic profiles of patients with type 2 diabetes mellitus
La deprescripción de insulina mediante agonistas del receptor de GLP-1 como estrategia terapéutica para mejorar el perfil metabólico en pacientes con diabetes mellitus tipo 2
Victor Perez de Arenaza Pozo
, Jersy Cárdenas Salas, Clotilde Vázquez Martínez
Corresponding author
Department of Endocrinology and Nutrition, University Hospital Fundación Jiménez Díaz, Madrid, Spain
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Parathyroid adenoma in the left inferior thyroid lobe.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Utku Soyaltin, Ayla Yildiz, Nurhilal Yusufoğlu, Emre İspir" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Utku" "apellidos" => "Soyaltin" ] 1 => array:2 [ "nombre" => "Ayla" "apellidos" => "Yildiz" ] 2 => array:2 [ "nombre" => "Nurhilal" "apellidos" => "Yusufoğlu" ] 3 => array:2 [ "nombre" => "Emre" "apellidos" => "İspir" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2530016424001368?idApp=UINPBA00004N" "url" => "/25300164/unassign/S2530016424001368/v1_202408210418/en/main.assets" ] "itemAnterior" => array:17 [ "pii" => "S2530016424000843" "issn" => "25300164" "doi" => "10.1016/j.endinu.2024.05.002" "estado" => "S200" "fechaPublicacion" => "2024-06-11" "aid" => "1488" "copyright" => "SEEN y SED" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "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" => "Insuficiencia cardíaca en personas con diabetes y obesidad: ¿se puede prevenir?" "tienePdf" => "es" "tieneTextoCompleto" => "es" "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Heart failure in people with diabetes and obesity, can it be prevented?" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jesús María de la Hera, Elías Delgado" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Jesús María" "apellidos" => "de la Hera" ] 1 => array:2 [ "nombre" => "Elías" "apellidos" => "Delgado" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2530016424000843?idApp=UINPBA00004N" "url" => "/25300164/unassign/S2530016424000843/v1_202406110419/es/main.assets" ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Potential of insulin deprescription adding a GLP-1 receptor agonist as a therapeutic strategy to improve the metabolic profiles of patients with type 2 diabetes mellitus" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Victor Perez de Arenaza Pozo, Jersy Cárdenas Salas, Clotilde Vázquez Martínez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Victor" "apellidos" => "Perez de Arenaza Pozo" "email" => array:1 [ 0 => "victor.parenaza@quironsalud.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Jersy" "apellidos" => "Cárdenas Salas" ] 2 => array:2 [ "nombre" => "Clotilde" "apellidos" => "Vázquez Martínez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Endocrinology and Nutrition, University Hospital Fundación Jiménez Díaz, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La deprescripción de insulina mediante agonistas del receptor de GLP-1 como estrategia terapéutica para mejorar el perfil metabólico en pacientes con diabetes mellitus tipo 2" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Type 2 diabetes mellitus (T2DM) is the 9th leading cause of death worldwide, affecting 462 million individuals. To change the natural progression of diabetes, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have emerged as renal and cardioprotective agents capable of achieving stable glycemic control. Currently available literature demonstrates their efficacy profile in preventing MACE-3, mitigating microvascular complications, and improving metabolic profiles, among other benefits. Within this context, an intriguing question arises: can GLP-1 RAs be used to reduce insulin doses?<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The aim of our study is to assess whether the addition of subcutaneous semaglutide (OW-semaglutide) once a week to adult patients with T2DM and eGFR >15<span class="elsevierStyleHsp" style=""></span>mL/min results in fewer insulin doses at the 12-month follow-up. We present a prospective study initiated in 2019 on the T2DM population from four Spanish hospitals located in Madrid, Spain. The study protocol was approved by the Fundación Jiménez Diaz Instituto de Investigación Sanitaria Local Ethics Committee. For this purpose, a total of 316 patients, utilizing various insulin regimens received additional OW-semaglutide and were monitored with visits at 6 and 12 months, during which multiple variables including insulin doses were collected.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Forty-four out of 316 initially registered patients discontinued subcutaneous semaglutide (13.9%), and 20 patients were lost to follow-up, mainly due to the pandemic. Ultimately, a total of 252 patients were eligible and included in the study. The baseline characteristics of our study population were: 61% were men, with a mean age of 62.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9.1 years and a mean course of T2DM of 14.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.5 years. Among the comorbidities reported, 88.8% had dyslipidemia; 84.1%, arterial hypertension; and 16.9% were smokers. Microvascular disease was present in 40.8% of patients (29.9% with diabetic nephropathy and 24.5% with diabetic retinopathy). Macrovascular complications included a past medical history of ischemic heart disease in 17.8% of the patients, acute myocardial infarction in 12.2%, stroke in 9.2%, and peripheral artery disease in 8.7%. Although 56.7% of the patients were categorized under primary prevention they had a very high cardiovascular risk, while 32.4% were categorized under secondary prevention. Baseline weight and BMI averaged 96.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.4<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> and 34.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.2<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, respectively. The mean HbA<span class="elsevierStyleInf">1c</span> level was 7.97<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.40%; mean eGFR (CKD-EPI), 79.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22.1<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>; and mean C-peptide, 2.73<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.6<span class="elsevierStyleHsp" style=""></span>ng/mL. Regarding basal antidiabetic treatment, 84.9% were on metformin, 47.6% on an SGLT2-inhibitor, 53.2% on a GLP-1 RA, 23.0% on a DPP4-inhibitor, 13.9% on repaglinide, 4.8% on a sulfonylurea, and 1.6% on pioglitazone.</p><p id="par0020" class="elsevierStylePara elsevierViewall">As depicted in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, the results revealed a significant reduction in the total number of insulin doses by 6<span class="elsevierStyleHsp" style=""></span>IU/day at 6 months and nearly 8<span class="elsevierStyleHsp" style=""></span>IU/day at 12 months. Both basal and rapid insulin doses exhibited decreases at both time periods (−3 and −5 for basal insulin at 6 and 12 months, respectively, and −3 and −2 for rapid insulin at the same intervals, respectively). Furthermore, 6.6% of patients discontinued their total insulin regimen, while notably, 26.1% of patients previously on rapid insulin discontinued this regimen by the end of the 12-month period. Only four patients initiated a rapid insulin regimen at the follow-up. The number of patients with ≥3 daily insulin injections decreased. Additionally, weight and HbA1c levels showed significant reductions at the follow-up (−4.4<span class="elsevierStyleHsp" style=""></span>kg and −0.77% at 12 months, respectively). Moreover, the number of patients achieving HbA1c levels <7% increased from 26.1% up to 54.6% at 12 months.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a multiple regression analysis to identify predictors of insulin dose reduction at 12 months following the initiation of OW-semaglutide. The independent variables included age, sex, course of T2DM, total insulin dose, baseline HbA1c levels (<7% vs ≥7%), BMI, C-peptide, and eGFR (<60 vs ≥60). Additionally, we considered the semaglutide dose achieved at 12 months (1.0<span class="elsevierStyleHsp" style=""></span>mg vs ≤0.5<span class="elsevierStyleHsp" style=""></span>mg), reductions in HbA1c levels and weight at the follow-up, the number of oral antidiabetic drugs used, basal antidiabetic treatment, and changes in antidiabetic treatment at the follow-up. Our analysis revealed that higher baseline insulin doses (beta −0.44), baseline HbA1c levels <7% (beta −0.17), greater reductions in weight at the follow-up (beta −0.04), eGFR ≥60<span class="elsevierStyleHsp" style=""></span>mL/min (beta −0.26), GLP-1 RA-naïve patients (beta −0.21), and initiation of metformin (beta −0.20) were independent predictors associated with greater reductions in insulin doses at 12 months.</p><p id="par0030" class="elsevierStylePara elsevierViewall">As evidenced by randomized controlled trials (RCTs) and real-world data (RWD) studies in the literature, our investigation confirms that the addition of a GLP-1 RA leads to a significant reduction in the daily insulin requirements of our patients. Regarding basal insulin, we saw that the addition of a GLP-1 RA can reduce insulin over-basalization in up to 46.6% of patients. In cases of patients on intensive therapy (>100<span class="elsevierStyleHsp" style=""></span>IU/day), numerous studies have explored the effect of adding liraglutide or exenatide, revealing notable reductions in HbA1c, weight, insulin dose, and glycemic variability (GV) as measured by continuous glucose monitor (CGM). We also observed a reduction in daily insulin injections, which could be associated with a decrease in lipodystrophies and improved glycemic control.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3–6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The significance of these studies lies in improving the quality of life, managing symptoms, mitigating organ damage, reducing the risk of hypoglycemia, and enhancing the overall prognosis of patients with T2DM by reducing insulin doses and improving disease control. Several investigations, such as the one conducted by Gamble et al. with 6072 patients have indicated that although high insulin doses may be associated with higher mortality rates, the risk also varies depending on the duration of insulin exposure, glycemic control, weight gain, and occurrences of cardiovascular events and hypoglycemia. It is obvious that the addition of GLP-1 RA to these patients led to better glycemic control while reducing insulin doses, thereby ameliorating disease comorbidities and mitigating adverse effects associated with insulin therapy.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4–9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, our findings suggest that the addition of OW-semaglutide to a Spanish population of T2DM patients led to fewer daily insulin dosage requirements, thereby contributing to improved metabolic profiles when combined with insulin deprescription. These results highlight the potential of insulin deprescription as a therapeutic strategy, underscoring the necessity for further trials to elucidate its efficacy profile and clinical applicability.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as mean (95% CI) for continuous variables and <span class="elsevierStyleItalic">n</span> (%) for categorical variables. A paired <span class="elsevierStyleItalic">t</span>-test and a symmetry test were performed for continuous and categorical variables, respectively, to compare baseline and follow-up variables.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Basal (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>252) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">6 months(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>252) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">12 months(<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>226) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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"><span class="elsevierStyleItalic">Maximum semaglutide dose (1.0</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mg)</span> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97 (38.5) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">175 (77.4) \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"><span class="elsevierStyleItalic">Total insulin (IU/day)</span> \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">55.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>43.2 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−6.1 (−8.2 to −4.1)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−7.7 (−10.4 to −4.9)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleItalic">Basal insulin (IU/day)</span> \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">44.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>27.9 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−3.2 (−4.6 to −1.9)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−5.3 (−7.2 to −3.4)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleItalic">Rapid insulin (IU/day)</span> \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">11.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22.1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−3.0 (−4.1 to −1.8)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−2.4 (−4.0 to −0.8)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleItalic">Total insulin (IU/kg/day)</span> \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">0.58<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.40 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.05 (−0.08 to −0.03)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.07 (−0.09 to −0.04)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleItalic">Weight (kg)</span> \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">96.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.4 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−3.1 (−3.8 to −2.3)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−4.4 (−5.4 to −3.5)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleItalic">HbA1c (%)</span> \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">7.97<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.40 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.82 (−1.01 to −0.63)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.78 (−0.98 to −0.58)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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"><span class="elsevierStyleItalic">No. of daily insulin injections</span> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleHsp" style=""></span>0 \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">0 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (3.6) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (6.6) \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"><span class="elsevierStyleHsp" style=""></span>1 \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">164 (65.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">176 (69.8) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">154 (68.1) \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"><span class="elsevierStyleHsp" style=""></span>2 \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">15 (6.0) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (4.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (4.0) \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"><span class="elsevierStyleHsp" style=""></span>3 \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">18 (7.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (4.8) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (5.3) \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"><span class="elsevierStyleHsp" style=""></span>4 \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">50 (19.8) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (15.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">31 (13.7) \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"><span class="elsevierStyleHsp" style=""></span>5 \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">5 (2.0) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (2.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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"><span class="elsevierStyleItalic">Stop total insulin</span> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9/252 (3.6%)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15/226 (6.6%)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleItalic">Stop basal insulin</span> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9/252 (3.6%)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15/226 (6.6%)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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"><span class="elsevierStyleItalic">Stop rapid insulin</span> \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20/82 (24.4%)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18/69 (26.1%)<a class="elsevierStyleCrossRef" href="#tblfn0005">**</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3620809.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes in main insulin treatment variables at the follow-up.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The benefit of insulin degludec/liraglutide (IDegLira) compared with basal-bolus insulin therapy is consistent across participant subgroups with type 2 diabetes in the DUAL VII randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.K. 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| 2024 October | 1 | 0 | 1 |
| 2024 September | 5 | 2 | 7 |
| 2024 August | 16 | 4 | 20 |
