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Obesidad y riesgo cardiovascular: liraglutida y sus beneficios terapéuticos=

 

Obesidad y riesgo cardiovascular: liraglutida y = sus beneficios terapéuticos

 


1<= /sup>

Washington Moises Moreira Mendoza

https://o= rcid.org/0009-0002-9177-2534

 

Estudiante de la Universidad Técnica de Manabí. Departamento Ciencias Médicas. Facultad Ciencias de la Salud. Portoviejo, Ecuador.

wmoreira0460@utm.edu.ec

2<= /sup>

Luis Enrique Bravo Vaca

https://o= rcid.org/0009-0008-8146-4486

 

Estudiante de la Universidad Técnica de Manabí. Departamento Ciencias Médicas. Facultad Ciencias de la Salud. Portoviejo, Ecuador.

 lbravo1588@utm.edu.ec

3<= /sup>

Mayker Armando Carbo Bazurto

=

https://o= rcid.org/0009-0008-0427-6895

 

Estudiante de la Universidad Técnica de Manabí. Departamento Ciencias Médicas. Facultad Ciencias de la Salud. Portoviejo, Ecuador.

 mcarbo1830@utm.edu.ec=

4<= /sup>

Eimy Marcela Del Valle Velez

https://o= rcid.org/0009-0000-2021-7862

 

Estudiante de la Universidad Técnica de Manabí. Departamento Ciencias Médicas. Facultad Ciencias de la Salud. Portoviejo, Ecuador.

 edelvalle1958@utm.edu.ec

5<= /sup>

Marjorie Briggitte Mendoza Pin=

https://o= rcid.org/0009-0008-7388-8625   

 

Estudiante de la Universidad Técnica de Manabí. Departamento Ciencias Médicas. Facultad Ciencias de la Salud. Portoviejo, Ecuador.

 mmendoza2947@utm.edu.ec

6<= /sup>

Jhon Alexander Ponce Alencastro

https://o= rcid.org/0000-0002-3666-7865

 

Docente de la Universidad Técnica de Manabí. Departamento Ciencias Médicas. Facultad Ciencias de la Salud. Portoviejo, Ecuador.

jhon.ponce@utm.edu.ec

 

 

 

 

A= rtículo de Investigación Científica y Tecnológica

E= nviado: 12/06/2024

R= evisado: 10/07/2024

A= ceptado: 05/08/2024

P= ublicado:25/08/2024

 DOI: https://doi.or= g/10.33262/ap.v6i3.1.526 <= o:p>

 

&nbs= p;

 

Cítese:

 

 

Moreira Mendoza, W. M., Bravo Vaca, L. E., Carbo Bazurto, M. A., Del Valle Velez, E. M., Mendoza Pin, M. B., & Ponce Alencastro, J. A. (2024). Obesidad y riesgo cardiovascula= r: liraglutida y sus beneficios terapéuticos. AlfaPublicaciones, 6(3.1), 165–183. https://doi.o= rg/10.33262/ap.v6i3.1.526

 

 

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E= sta revista está protegida bajo una licencia Creative Commons Attribution Non Commercial No Derivatives 4.0 International. Copia de la licencia: http://creativecommons.org/licenses/by-nc-nd/4.0/

 

Palabras claves:

Obesidad; riesgos cardiovasculares; liraglutid= a; tratamiento.

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Resumen

Introducción: La obesidad es una enfermedad crónica, compleja y recurrente, considerada como un factor de riesgo de múltiples enfermedades, entre ellas, las que están relacionadas= al sistema cardiovascular; actualmente estos riesgos se han vistos disminuid= os por el uso de la liraglutida en el tratamiento para pacientes obesos, demostrando una notable disminución del apetito y aumento de la saciedad,= por ende, mejora las funciones metabólicas, promueve la secreción de insulina= y disminuye el vaciamiento gástrico; este medicamento es muy bien tolerado y altamente eficaz, lo que justifica su alto costo. Objetivo: Descri= bir los beneficios terapéuticos en la obesidad y el riesgo cardiovascular generando conocimientos de la situación terapéutica actual de la liraglut= ida. Metodología: Se realizó un estudio descriptivo documental utilizando descriptores para buscar literatura relevante en bases de datos como Scopus, Elsevier y PubMed, tanto en español como en inglés. La búsqu= eda se efectuó a través de Google Académico con operadores booleanos para afi= nar los resultados. Se recolectaron, revisaron y analizaron las fuentes bibliográficas, gestionadas con Mendeley, seleccionando 29 artículos recientes y relevantes sobre los beneficios terapéuticos de la liraglutid= a en la obesidad y el riesgo cardiovascular. Resultados: La Liraglutida es un análogo del GLP-1 humano con 97% de homolo= gía, adecuado para dosis diarias en pacientes con diabetes tipo 2. Absorbida lentamente, su vida media es de aproximadamente 10-14 horas. Tiene como función reducir la glucosa, apetito y riesgos cardiovasculares. Su metabolismo es similar al GLP-1 nativo, y se elimina a través del hígado y riñones. C= onclusión: La liraglutida como agonista del GLP-1 demostró ser efectivo en la reducción= del peso corporal y el apetito, esto se evidenció gracias a estudios y metaanálisis, donde se demostró que mejora las funciones metabólicas en el paciente; uno de sus efectos es la mejoría general del perfil glucémico, causando una disminución de incidencia de enfermedades cardiovasculares c= omo HA, DT2 e IAM. <= b>Á= rea de estudio general: Medicina. Área de estudio específica: F= armacología. T= ipo de artículo: revisiones bibliográficas.

 

 

Keywords:

Obesity; Cardiovascular risk; Liraglutide; Treatment.

 

Abstract

Introduction: Obesity is a chronic, complex and recurrent disease, considered a risk fa= ctor for multiple diseases, including those related to the cardiovascular syst= em; currently these risks have been reduced by the use of liraglutide in the treatment of obese patients, demonstrating a notable decrease in appetite= and increase in satiety, therefore, it improves metabolic functions, promotes insulin secretion and decreases gastric emptying; this drug is very well tolerated and highly effective, which justifies its high cost. Objective: To describe the therapeutic benefits in obesity and cardiovascular risk, generating knowl= edge of the current therapeutic situation of liraglutide. Methodology: A descriptive documentary study was conducted us= ing descriptors to search for relevant literature in databases such as Scopus= , Elsevier, and PubMed, both in Spanish and English. The search was conducted through Google Scholar with Boolean operators to refine the results. The bibliographic sources were collected, reviewed, and analyzed, managed with Mendeley, selecting 29 recent and relevant articles on the therapeutic benefits of liraglutide in obesity and cardiovascular risk. Results: Liraglutide is a human= GLP-1 analogue with 97% homology, suitable for daily doses in patients with typ= e 2 diabetes. Absorbed slowly, its half-life is approximately 10-14 hours. Its function is to reduce glucose, appetite, and cardiovascular risks. Its me= tabolism is like native GLP-1, and it is eliminated through the liver and kidneys.= Conclusion: Liraglutide as a GL= P-1 agonist proved to be effective in reducing body weight and appetite, this= was evidenced by studies and meta-analysis, where it was shown to improve metabolic functions in the patient; one of its effects is the general improvement of the glycemic profile, causing a decrease in the incidence = of cardiovascular diseases such as HA, T2D and AMI.

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Introducción

La obesidad, considerada una enfermedad crónica, compleja y recurrente, es un factor de riesgo para numerosas patologías, en especial las enfermedades cardiovasculares, que afectan significativamente la calidad de vida del paciente. Esta afección no solo contribuye al desarrollo de condiciones com= o la hipertensión, la diabetes tipo 2 y la dislipidemia, sino que también está asociada con un mayor riesgo de eventos cardiovasculares adversos, como el infarto agudo de miocardio y el accidente cerebrovascular (Alruwaili et al., 2021).

En los últimos año= s, se ha prestado especial atención a la liraglutida como tratamiento para la obesidad. Este medicamento, un agonista del receptor GLP- 1 (glucagón-1ike peptide-1), ha demostrado una notable eficacia en la reducción del consumo = de alimentos, la disminución del peso corporal y la mejora de las funciones metabólicas (Alruwaili et al., 2021).

La liraglutida no = solo actúa en los receptores pancreáticos y gástricos, promoviendo la secreción = de insulina y retrasando el vaciamiento gástrico, sino que también influye en áreas subcorticales del cerebro, aumentando considerablemente la sensación = de saciedad. Los estudios en roedores han sido cruciales para este avance, mostrando que la administración de agonistas del receptor GLP-1 reduce a co= rto plazo la ingesta de alimentos y agua, resultando en una disminución del peso corporal (Alruwaili et al., 2021).

En sujetos obesos tratados con GLP-1, se observó un prolongado período de saciedad postprandi= al y una disminución en el vaciamiento gástrico. A pesar de su costo elevado, la liraglutida es un medicamento bien tolerado y altamente eficaz, justificand= o su uso debido a beneficios en la pérdida de peso y la reducción del riesgo de enfermedades cardiovasculares (Alruwaili et al., 2021).

El objetivo del presente estudio es describir los beneficios terapéuticos en la obesidad y = el riesgo cardiovascular generando conocimientos de la situación terapéutica actual de la liraglutida. Este estudio proporcionará una visión integral del potencial terapéutico del medicamento, contribuyendo a una mejor comprensió= n y manejo de la obesidad y complicaciones relacionadas al sistema cardiovascul= ar.

Metodología

Se llevó a cabo un estudio de tipo descriptivo documental. Para la identificación de las fuent= es relevantes, se utilizaron los descriptores DeCS/ MeSH, seleccionando las palabras clave “obesidad”, “riesgo cardiovascular”, “liraglutida” y “tratamiento”. Estas palabras clave fueron empleadas para realizar una búsq= ueda exhaustiva de literatura en bases de datos reconocidas como Scopus, Elsevie= r y PubMed, tanto en español como en inglés.

Esta búsqueda se realizó a través del motor de búsqueda Google Académico, utilizando operado= res booleanos AND, OR Y NOT para refinar y optimizar los resultados. Posteriormente, se llevó a cabo la recolección, revisión y análisis de las fuentes bibliográficas encontradas.

La organización y gestión de las referencias bibliográficas se realizó mediante el gestor Mendeley. Este proceso permitió seleccionar un total de 29 fuentes bibliográficas pertinentes, las cuales cumplieron con los criterios de selección establecidos como artículos de alto impacto, publicaciones de revisión y completos, bibliografía menor a 6 años. Estas fuentes pertenecen= a la literatura más actual y relevante, destacando los beneficios terapéutico= s de la liraglutida en el tratamiento de la obesidad y la reducción del riesgo cardiovascular. Buscando dar respuesta a la siguiente pregunta planteada en= la presente investigación. ¿Cuáles son los beneficios terapéuticos de la Liraglutida en la obesidad y riesgos cardiovasculares? 

En cada etapa del proceso, se aseguró la rigurosidad científica y la integridad de los datos, garantizando que las fuentes seleccionadas proporcionaran evidencia sólida y actualizada sobre el tema de estudio.

Resultados

Luego de una investigación sistematizada en = los descriptores ya mencionados, logramos recaudar datos relevantes acerca de c= ada una de las palabras claves para poder definir con claridad el concepto más adecuadas de estas:

Obesidad

Según Kaufer-Horwi= tz et al. (2022), la obesidad se considera una epidemia mundial del siglo XXI,= que de acuerdo con la Organización Mundial de la Salud (OMS), se considera como= la acumulación anormal o excesiva de tejido adiposo en relación con el peso, lo cual puede ser perjudicial para la salud. Esta acumulación excesiva de grasa suele ir acompañada de una inflamación sistémica crónica leve lo que le da = la característica de una entidad patológica. Recientemente, ha sido reconocida como una enfermedad crónica y recurrente de origen multifactorial y caracterizada por un desequilibrio energético debido a un estilo de vida sedentario, un consumo excesivo de energía, o ambos (Kaufer-Horwitz et al., 2022). De acuerdo con todo lo antes mencionado, la obesidad es el resultado= de una compleja interacción entre genes y ambiente, donde los cambios en la alimentación y el estilo de vida asociados a la urbanización y el desarroll= o de las sociedades han favorecido al desarrollo de factores predisponentes como= la expresión de los genes. En este contexto el Índice de Masa Corporal (IMC= ), constituye una herramienta fundamental para el diagnóstico y el tratamiento= de la obesidad, ya que proporciona de manera sencilla y rápida la identificaci= ón de aquellos individuos que se encuentran en riesgo. A pesar de que el IMC no distingue entre la su alta correlación con el porcentaje de la masa corpora= l lo convierte en un indicador de gran utilidad. El IMC se calcula dividiendo el peso de la persona en kilogramos por el cuadrado de la estatura en metros. = En una persona adulta un IMC entre 25 y 29.99 es considerado sobrepeso de grado 1., un IMC que se encuentre entre los valores de 30 a 39.99 constituye sobrepeso de grado 2 y un IMC por encima de 40 es obesidad de grado 3 (Dietz & Robinson, 1998) (tabla 1).  <= o:p>

Tabla 1<= o:p>

<= span style=3D'mso-bidi-font-size:12.0pt;line-height:115%;mso-fareast-font-family= :"Times New Roman"; mso-bidi-font-family:"Times New Roman";mso-ansi-language:ES-EC;mso-bidi-lan= guage: SI-LK;mso-bidi-font-weight:bold'>Clasificación del IMC por la OMS

Valores límites del IMC

Ba= jo Peso

&l= t;18,5 kg/m2

No= rmopeso

18= ,5 - 24,9 kg/m2

So= brepeso o Pre-Obeso

25= ,0 - 29,9 kg/m2

Ob= esidad Grado I o moderada

30= ,0 - 34,9 kg/m2

Ob= esidad Grado II o severa

35= ,0 - 39,9 kg/m2

Ob= esidad Grado III o mórbida

&#= 8805; 40,0 kg/m2

Fuente: Dietz & Robinson (1998)

La obesidad al ser= un factor predisponente a la aparición de determinadas enfermedades como la hipertensión, diabetes y dislipidemia; es desde estas comorbilidades que se afecta las dimensiones biológicas, psicológicas y sociales del ser humano impactando en la calidad de vida y el bienestar personal por los costos directos e indirectos que la carga de esta enfermedad genera a largo plazo, sobre todo en aquellas personas con recursos limitados o con una capacidad = de autocuidado deficiente.

Esta patología rel= acionada con el peso implica la participación de múltiples factores, los cuales evolucionan a lo largo de los años e implican una interacción entre los gen= es, la epigenética, el microbioma, el metabolismo y el comportamiento del individuo. Todo esto combinado se desencadena por elementos ambientales a través de un mecanismo del que no se tiene comprensión actualmente. Además, otro factor que contribuye es el cambio de los sistemas alimentarios, pero = es probable que sean los factores biológicos de cada persona los que contribuy= en a que el individuo sea más susceptible a la obesidad (Hjorth et al., 2023).

En cuanto a la fisiopatología del peso corporal en este problema de salud, se identifican = dos procesos principales: Primero, el restablecimiento del punto de ajuste del = peso corporal y por otro lado, se encuentra el equilibrio de la energía positiva prolongada. También, existen múltiples mecanismos fisiopatológicos que afec= tan al apetito y que contribuyen al desarrollo de esta condición preocupante. Específicamente, el apetito se encuentra influenciado por la interacción en= tre el sistema nervioso central y el sistema endocrino, a través del cual las señales de los órganos periféricos se transmiten al sistema nervioso central (Asadi et al., 2022).

De manera que enfrentar la obesidad requiere una valoración médica completa y meticulosa = del paciente, esto permite no solo determinar el grado de sobrepeso u obesidad, sino también comprender las causas subyacentes que la originan. A partir de este análisis exhaustivo, se espera conocer la estrategia terapéutica más adecuada para cada caso (Alarcón-Sotelo et al., 2018).

Si bien la dieta, = el ejercicio y la cirugía bariátrica han sido pilares fundamentales en el tratamiento de la obesidad, sus limitaciones han impulsado la búsqueda de herramientas farmacológicas complementarias. La obesidad, por su complejida= d, exige un abordaje integral que incluya estas alternativas, siempre bajo la supervisión de un profesional médico (Alarcón-Sotelo et al., 2018).

ha aprobado cinco estrategias farmacológicas para combatir la obesidad, las cuales son: orlis= tat (Xenical, Alli), fentermina - topiramato (Qsymia), naltrexona - bupropión (Contrave), liraglutida (Saxenda) y la lorcaserina, destacando en base a tr= es estudios de estas la liraglutida, que se posiciona como una herramienta efi= caz para el tratamiento de esta condición (Alarcón-Sotelo et al., 2018).

Riesgo cardiovascular<= /p>

Las Enfermedades Cardiovasculares (ECV) son las principales causas de morbilidad y mortalidad a nivel global (Toth, 2021). En consecuencia, Velasco menciona q= ue la obesidad es considerada una pandemia del presente siglo por encontrarse asociada con graves enfermedades crónicas no transmisibles, especialmente el riesgo de padecer enfermedades cardiovasculares (Velasco & Velasco, 202= 3). En base a las razones antes dichas Cercato et al. Menciona que una de las principales causas son la dislipidemia, la resistencia a la insulina, la hipertensión arterial (HTA), y aterosclerosis tanto en adultos como en niños (Cercato & Fonseca, 2019). 

Los pacientes con diabetes tipo 2 (DT2) tienen un riesgo particular de sufrir eventos cardiovasculares adversos por lo que el uso de antidiabéticos no solo debe = de centrarse en el control de la glucosa, sino que también deben generar efect= os beneficiosos en la reducción del riesgo cardiovascular, condición imprescindible para que estas enfermedades crónicas se compensen y mantiene= n la homeostasis de la reserva órgano-funcional (Wronka et al., 2023).

Teniendo estudios = que corroboran lo antes mencionado como el ensayo clínico aleatorizado realizado por Buse et al (Buse et al., 2020). en donde se evaluaron los riesgos cardiovasculares en aquellos pacientes con DT2, el mismo que demostró que existía una disminución de estos riesgos como muerte cardiovascular, infart= o de miocardio e incluso accidentes cerebrovasculares no fatales. Dicho análisis observatorio identificó que los agonistas del GLP-1R, en este caso la lirag= lutida, mejoraba los riesgos cardiovasculares relacionado con este agonista que red= uce la hemoglobina glucosilada (HbA1c) y también el peso corporal, acompañado c= on reducciones pequeñas, pero de gran importancia de la tensión arterial sistólica, cabe mencionar que la liraglutida también tiene efectos antiinflamatorios y anti escleróticos. La HbA1c junto con la UACR (relación= de Albúmina-Creatinina Urinaria), son los mediadores potenciales beneficiosos = para la reducción de riesgos cardiovasculares. La HbA1c media hasta un 83% de efectos beneficiosos y, la UACR alrededor de un 33%; sin dejar de lado otros factores como el peso corporal y la tensión arterial que también son mecani= smos beneficiosos, solo que con efectos menores. En sí, la disminución de la HbA= 1c contribuye a la reducción de riesgos cardiovasculares (Buse et al., 2020).<= o:p>

Haciendo referenci= a a los beneficios de la liraglutida de Vemulapalli et al. (2023), sostiene que= la liraglutida reduce significativamente el riesgo de eventos cardiovasculares adversos mayores (ECAM), infarto de miocardio (IAM), mortalidad CV y mortal= idad por todas las causas. No se encontraron diferencias significativas entre los grupos de liraglutida y control en cuanto al resultado de accidente cerebrovascular. Sin embargo, el análisis de sensibilidad reveló una reducc= ión significativa del riesgo de accidente cerebrovascular entre los pacientes q= ue tomaban liraglutida como podemos apreciar en la tabla 2 (Vemulapalli et al., 2023).

Tabla 2<= o:p>

<= span style=3D'mso-bidi-font-size:12.0pt;line-height:115%;mso-fareast-font-family= :"Times New Roman"; mso-bidi-font-family:"Times New Roman";mso-ansi-language:ES-EC;mso-bidi-lan= guage: SI-LK;mso-bidi-font-weight:bold'>Beneficios de la liraglutida en condicione= s patológicas de riesgo cardiovascular

Condiciones Patológica= s de Riesgo Cardiovascular

Estudios realizados

MA= CE

La combinación de los resultados de 11 estudios evaluó los resultados de MACE. La liraglutida redujo significativamente el riesgo de MACE en comparación con el grupo de control (RR =3D 0,89; IC de= l 95 %: 0,84-0,93; P < 0,00001; I2 =3D 0 %).

In= farto Agudo de Miocardio

Se combinaron doce estudios para evaluar la incidencia de infarto de miocardio. La liraglutida redujo significativame= nte la incidencia de infarto de miocardio en comparación con el grupo de cont= rol (RR =3D 0,88; IC del 95 %: 0,78-1,00; P =3D 0,04; I2 =3D 39 %). El anális= is de sensibilidad confirmó resultados consistentes con heterogeneidad reducida (RR=3D0,83; IC del 95%: 0,74-0,92; P=3D0,0005; I2=3D0%).

 

Tabla 2<= o:p>

<= span style=3D'mso-bidi-font-size:12.0pt;line-height:115%;mso-fareast-font-family= :"Times New Roman"; mso-bidi-font-family:"Times New Roman";mso-ansi-language:ES-EC;mso-bidi-lan= guage: SI-LK;mso-bidi-font-weight:bold'>Beneficios de la liraglutida en condicione= s patológicas de riesgo cardiovascular (continuación)

Co= ndiciones Patológicas de Riesgo Cardiovascular

Es= tudios realizados

Ac= cidente Cerebrovascular

Seis estudios evaluaron los resultados del accidente cerebrovascular. No se encontraron diferencias significativas e= ntre los grupos de liraglutida y control (RR =3D 0,85; IC del 95 %: 0,73-1,00;= P =3D 0,05; I2 =3D 44 %). El análisis de sensibilidad indicó una incidencia de accidente cerebrovascular significativamente menor en el grupo de liraglu= tida con heterogeneidad reducida (RR =3D 0,82; IC del 95 %: 0,69-0,98; P =3D 0= ,03; I2 =3D 22 %).

Mu= erte por ECV

Se agruparon ocho estudios para evaluar la mue= rte por ECV. La liraglutida redujo significativamente la incidencia de muerte= por ECV en comparación con el grupo de control (RR =3D 0,70; IC del 95 %: 0,57-0,85; P =3D 0,0003; I2 =3D 65 %). El análisis de sensibilidad mantuvo resultados consistentes con una heterogeneidad significativamente reducida (RR=3D0,79; IC del 95%: 0,71-0,88; P<0,0001; I2=3D0%).

Mu= erte por todas las causas

Se agruparon los datos de diez estudios para evaluar la muerte por todas las causas. La liraglutida redujo significativamente la incidencia de muerte por todas las causas en comparación con el grupo de control (RR =3D 0,87; IC del 95 %: 0,80-0,94;= P =3D 0,0003; I2 =3D 0 %).

Fuente: Vemulapalli et al. (2023)

Sin embargo, su impacto en la función cardíaca de los pacientes con diabetes tipo 2 ha gene= rado resultados diversos, algunos contradictorios. Mientras que ciertos estudios indican un efecto beneficioso para el sistema cardiovascular, otros no obse= rvan mejoras significativas e incluso reportan efectos adversos.

Un meta análisis q= ue incluyó cinco ensayos controlados con un total de 220 participantes mostró = que la liraglutida mejoró significativamente varios aspectos de la función card= íaca en pacientes con diabetes tipo 2, como la capacidad del ventrículo izquierdo para bombear sangre y la eficiencia del corazón en la circulación sanguínea. Sin embargo, no se encontraron mejoras significativas en la cantidad total = de sangre bombeada por minuto ni en otros parámetros específicos de la función diastólica (Xia et al., 2024).

En contraste, otro estudio cruzado de doble ciego con 30 pacientes que padecían de enfermedad coronaria estable y diabetes tipo 2 recién diagnosticada, se encontró como resultado que la liraglutida no mejoró la función diastólica y que de hecho, deterioró la velocidad e', esto es posiblemente debido a un aumento de la frecuencia cardíaca inducida por la terapia (Kumarathurai et al., 2021).

Otro metaanálisis,= que evaluó la eficacia de la liraglutida en la mejora de la miocardiopatía diabética, concluyó que la liraglutida disminuyó el llenado diastólico temp= rano y la presión de llenado del ventrículo izquierdo, pero también redujo la función sistólica dentro del rango normal (Bizino et al., 2019).=

Estas evidencias planteadas sugieren que la liraglutida tiene el potencial de mejorar algunos aspectos en cuanto a la función cardíaca en pacientes con DT2, concluyendo = que sus efectos en la función cardiovascular varían dependiendo del contexto clínico específico utilizado, tomando en cuenta la especificidad de los individuos, por ende, es necesario considerar estos aspectos cuando se eval= úa el uso de liraglutida en el manejo de la función cardíaca en pacientes con = DT2 y continuar investigando para comprender mejor sus efectos a largo plazo.

Liraglutida

Según Jacobsen et = al. (2016), consideran a la liraglutida como un análogo del GLP-1 humano, con un 97% de homología con el GLP-1 nativo (con el reemplazo de la lisina 34 por arginina y la incorporación de una molécula de ácido graso en la posición 2= 6), el cual debido a sus propiedades farmacocinéticas hacen que sea adecuada una sola dosis al día en pacientes con DT2.

Según Jacobsen et = al. (2016), la liraglutida tiene una absorción lenta después de la inyección subcutánea, con un tiempo máximo de aproximadamente 12 horas. Una vida medi= a de entre 10 a 14 horas, haciendo que sea adecuada la administración de una dos= is al día, gracias a su efectividad de aproximadamente 24 horas sobre el contr= ol de la glucemia; Su vía de distribución tiene lugar en el líquido intravascu= lar y el compartimento extracelular, lo que se alinea con su alto grado de unió= n a la albúmina; su metabolismo tiene una vía similar a la del GLP-1 nativo, pe= ro más lento con escisión por DPP-4  (Dipeptidil Peptidasa 4) y NEP (Endopeptidasa Neutra) en varios metabolitos  y se degrada completam= ente en péptidos, aminoácidos y fragmentos de ácidos grasos dentro del cuerpo, q= ue posterior a eso tiene una eficaz eliminación por medio del hígado y riñones (Jacobsen et al., 2016).

Sus acciones farmacodinámicas incluyen un mejor control de la glucosa, reducción del apetito, ingesta energética y perfiles lipídicos después de cada comida disminuidos.

 <= /span>

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Estructu= ra y propiedades de la liraglutida

La liraglutida es = un agonista del receptor GLP-1 de acción prolongada, es homólogo en el GLP-1 nativo humano en 97%, el cual se añade una cadena lateral de palmitato en la posición 26 utilizando un espaciador de ácido γ-glutámico y el reempla= zo de la lisina 34 por arginina; este análogo se administra una vez al día (Yo= usef et al., 2021). Puede reducir el peso corporal a través de sus efectos sobre= el sistema nervioso central y la regulación del vaciamiento gástrico (Maselli = et al., 2022), presenta diversos efectos beneficiosos en el contexto del tratamiento de la diabetes tipo 2 y la obesidad, por ejemplo, puede disminu= ir la glucosa plasmática por sus efectos sobre la secreción de insulina y gluc= agón y por la desaceleración del vaciamiento gástrico. Además, se ha demostrado = que la liraglutida reduce los eventos cardiovasculares (infarto de miocardio, accidente cerebrovascular y mortalidad asociada) (Nauck et al., 2021). Apar= te de regular la glucosa en sangre, se ha informado que la liraglutida tiene un efecto protector contra daños a tejidos y órganos en varios modelos animales (Xu et al., 2023).

Metaboli= smo de la liraglutida

La incorporación de una cadena lateral de palmitato en la posición 26 logra que la liraglutida = se enlaza fuertemente a la albúmina, dando como resultado un 99% de unión a comparación con el GLP-1 natural. Gracias a esto, la liraglutida evade el filtrado glomerular, lo que causa un mayor efecto de acción. Los metabolito= s de la liraglutida suelen detectarse en la orina y en las heces, para finalmente llegar a metabolizar de manera hepática y se elimina principalmente a travé= s de los riñones y el hígado (Mariam & Niazi, 2024). Algunos ensayos realiza= dos en sujetos varones sanos que recibieron múltiples dosis subcutáneas de liraglutida reportaron un tiempo de concentración plasmática máxima de 12 h= oras y una vida media de eliminación plasmática, t 1/2, que oscilaba entre 10 a = 14 horas, dependiendo de la manera de dosificarse (Deng et al., 2022).

Mecanismo principal de la liraglutida como neuroprotector

La liraglutida imi= ta la acción del GLP-1 al unirse a receptores específicos en las células beta pancreáticas, aumentando la secreción de insulina y mejorando el control glucémico en pacientes con diabetes tipo 2. Este polipéptido se descompone = en aminoácidos mediante proteasas y es poco probable que cause daño hepático directo; trabaja mediante la vía de las incretinas, afectando el metabolism= o de la glucosa, y se clasifica junto a otros tratamientos antidiabéticos como l= os inhibidores de DPP-4 (sitagliptina, saxagliptina, linagliptina) y otros análogos de GLP-1 (exenatida) (National Institute of Diabetes and Digestive and Kidney Diseases, 2020).

El GLP-1, secretado tras las comidas en el íleon distal, colon proximal y núcleo vagal, regula = la glucosa en sangre al inhibir la secreción de glucagón y mejorar la secreció= n de insulina de manera dependiente de la glucosa. Además, el GLP-1 ralentiza el vaciado gástrico, induce saciedad y reduce el apetito, actuando en el hipotálamo, sistema límbico y la corteza. La farmacodinamia de la liragluti= da es compleja, ya que interviene en varios niveles para mantener la homeostas= is de la glucosa regulando la supervivencia de las células beta, la secreción de insulina y la conducta alimentaria (Tak & Lee, 2021).

Liraglut= ida como anorexígeno y quemador de calorías en la obesidad; y sus efectos cardioprotectores

El mecanismo de ac= ción de la liraglutida se basa en actuar sobre regiones del cerebro realizando u= na imitación de la hormona GLP-1 y así controlar el apetito y la saciedad, a su vez aumenta en menor medida el gasto energético, ya que incrementa el nivel= de insulina postprandial de una manera dependiente de la glucosa, retrasa el vaciamiento gástrico, reduce la secreción de glucagón e induce la pérdida de peso a través de la reducción del apetito y la ingesta de energía (Kelly et al., 2020).

La liraglutida es transportada al hipotálamo por tanicitos, células ependimogliales especializadas que expresan el receptor GLP1R y absorben el fármaco de la sangre. Una vez activada, induce su exocitosis hacia el líquido cefalorraqu= ídeo (LCR), donde se une a receptores GLP1R en las neuronas hipotalámicas, regul= ando la homeostasis energética. Además, actúa en el sistema límbico de recompens= a y la corteza cerebral (Tak & Lee, 2021).

Tanto estudios preclínicos como observaciones clínicas demostraron que el agonista del receptor de GLP-1 es eficaz para aumentar la actividad de GLP-1 y proteger = el corazón contra la hipertensión, la hipertrofia y la fibrosis, lo que va más allá de los beneficios logrados como agente antidiabético. La protección cardiovascular de la liraglutida está mediada por la modulación de la expre= sión de Ang II AT1R/AT2R y el receptor de GLP-1 (GLP-1R) (Tak & Lee, 2021).<= o:p>

Fármacos agonistas GLP-1 disponibles en el tratamiento de la obesidad y riesgo cardiovascular; y sus inconvenientes

Según el tiempo de activación del receptor de los agonistas GLP-1 se dividen en dos grupos: aquellos compuestos de acción corta que se activan a corto plazo del recept= or GLP-1, los mismos que alcanzan una concentración ideal en pocas horas pero,= al cabo de entre 6 a 10 horas sus concentraciones disminuyen repentinamente; y tenemos al otro grupo que es de acción prolongada, estos activan sus recept= ores de forma prolongada, tanto así, que se puede administrar una vez al día o incluso una vez a la semana (Klen & Dolžan, 2022; Nauck, 2016).

Agonista del GLP-1R de acción corta. exenatida: es uno de los análogos más estudiados, comparte un alrededor del 50% de los aminoácidos con el GLP-1 humano, además tiene una gran afini= dad por sus receptores, tiene una vida media de 24h, se administra dos veces al día, su excreción tiene lugar en los riñones (Klen & Dolžan, 2022; Nauc= k, 2016). lixisenatida: tiene una gran unión al GLP-1R, el 55% está uni= do a proteínas, tiene una vida media de 3 horas, se administra diariamente, su excreción se da a través de filtración glomerular seguida de reabsorción tubular (Klen & Dolžan, 2022; Nauck, 2016).

Agonista del GLP-1R de acción prolongada. = La liraglutida es una forma del GLP-1 pero modificada, se administra por vía subcutánea una vez al día teniendo un control eficaz de glucosa de 24 h, tiene una concentración plasmática de 9h a 14h (media de 13h), el 97% de la liragluti= da se une a proteínas plasmáticas, su metabolismo es similar a proteínas grand= es. En este grupo también encontramos a la dulaglutida que es homólogo en un 90= % al GLP-1, la semaglutida con un 94% de aminoácidos similar al GLP-1 nativo y l= a efpeglenatida que, en comparación con los otros agonistas de acción prolongada, se asocia= en la descomposición más rápida del GLP-1R permitiendo que más receptores de la superficie celular permanezcan disponibles para la señalización (Klen & Dolžan, 2022; Nauck, 2016).

Después del inicio temprano del tratamiento de cualquiera de estos agonistas, aparecen efectos secundarios como las náuseas, vómitos y diarreas, los cuales dependen de la dosificación administrada, además, estos agonistas se asocian con un riesgo= muy bajo de hipoglucemia, pero solo en casos cuando se usa en combinación con o= tros agentes antihiperglucemiantes (Klen & Dolžan, 2022; Nauck, 2016).<= /o:p>

Tratamiento: implicaciones terapéuticas de l= a liraglutida

La liraglutida es = un agonista del receptor GLP-1 de larga duración, sintetizado mediante tecnolo= gía de ADN recombinante. Se administra mediante inyecciones subcutáneas diarias debido a su baja biodisponibilidad oral (Wronka et al., 2023).

El tratamiento se inicia con 0,6 mg al día durante 1 semana. Esta dosis inicial está destinad= a a reducir los síntomas gastrointestinales. Después de 1 semana, la dosis se aumenta a 1,2 mg y puede aumentarse aún más a 1,8 mg según el control glucé= mico individual (Nauck, 2016).

Efectos secundarios de la liraglutida

Los efectos secundarios más comunes del tratamiento incluyen síntomas digestivos como diarrea, náuseas y vómitos, así como otros como dolor de cabeza, mareos, erupción cutánea, fatiga, taquicardia leve e infecciones respiratorias superiores. Sin embargo, estos efectos tienden a disminuir con el tiempo y pueden prevenirse mediante un aumento gradual de la dosis. Es fundamental monitorear de cerca los síntomas gastrointestinales, ya que un incremento significativo podría llevar a deshidratación y daño renal agudo. Además, los agonistas del receptor GLP-1 han sido vinculados con un mayor riesgo de enfermedad de la vesícula biliar y problemas pancreáticos. La administració= n del tratamiento puede causar enrojecimiento y erupción en el lugar de la inyecc= ión. Aunque se ha especulado sobre la posibilidad de que el tratamiento contribu= ya al cáncer medular de tiroides, estas preocupaciones aún no han sido corroboradas (Wronka et al., 2023).

Mujeres embarazada= s o aquellas con hipersensibilidad a los agonistas del receptor GLP-1 deben evi= tar el uso de medicamentos de esta clase. Asimismo, personas con enfermedad gastrointestinal severa o gastroparesia no deben recibir este tratamiento. = Individuos con riesgo elevado o antecedentes de pancreatitis hemorrágica o necrosante,= así como aquellos con historial de cáncer medular de tiroides o síndrome de neoplasia endocrina múltiple tipo 2, también deben evitar los agonistas del receptor GLP-1. Aunque estos fármacos son generalmente seguros, su uso ampl= io en pacientes con diabetes tipo 2 para reducir eventos cardiovasculares debe evaluarse considerando el balance entre beneficios y riesgos. La elección d= e la terapia hipoglucemiante debe ser personalizada, teniendo en cuenta el perfi= l de riesgo y los beneficios específicos para cada paciente (Wronka et al., 2023= ).

Conclusiones

·&nb= sp;        La liraglutida como agonista del GLP-1R ha demostrado ser efectiva an= te la reducción del peso corporal y el apetito. Estudios y metaanálisis han evidenciado que este medicamento no solo contribuye en la inhibición del apetito, sino que mejora de manera significativa las funciones metabólicas aumentando la sensación de saciedad en los pacientes, reduciendo así factor= es de riesgo que se encuentran relacionado con la obesidad, como las enfermeda= des cardiovasculares. 

·&nb= sp;        Los efectos causados por el uso de este medicamento han favorecido en= la mejoría general del perfil glucémico de los pacientes, entre los cuales se destacan una mejoría en la salud cardiovascular. Los estudios analizados han demostrado esto, concluyendo en que el uso de este fármaco reduce la incide= ncia de las enfermedades cardiovasculares categorizadas como graves, entre ellas= la hipertensión arterial, los ACV y el infarto agudo de miocardio.<= /span>

Conflicto de intereses

Los autores declar= an que no existe conflicto de intereses en relación con el articulo presentado= .

Declaración de contribución = de los autores

Cada uno de los autores contribuyeron con la esquematización, escritura, revisión y edición= del artículo. Autores principales y quienes desarrollaron el respectivo estudio= W.M.M.M; L.E.B.V; M.A.C.B; E.M.D.V y M.B.M.P, colaboración y verificación de resulta= dos Dr. J.A.P.A. Todos los autores han leído y aceptado la versión escrita del manuscrito.

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El artículo que se publica es de exclusiva responsabilidad de los autores y no necesariamente reflejan el pensamiento de la Revista Alfa Publicaciones.

 

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