[Impact of a primary care pharmacy unit on the optimization of pharmacological treatment of type 2 diabetic patients]. / Impacto de una unidad de farmacia de atención primaria en la optimización del tratamiento farmacológico de pacientes diabéticos tipo 2.

OBJECTIVE: To evaluate the impact of a pharmaceutical intervention on treatment optimization in patients with type 2 diabetes mellitus. DESIGN: Before-after intervention study. SITE: Health centers of the Primary Care Department of Camp de Tarragona. PARTICIPANTS: Patients aged ≥ 18 years, diagnosed with type 2 diabetes mellitus and under treatment with antidiabetic drugs. INTERVENTIONS: Review of pharmacological treatment for type 2 diabetes mellitus and issuance of proposals for its adequacy. MAIN MEASUREMENTS: Demographic and clinical variables were collected to assess the adequacy of antidiabetic treatment. A consensus meeting was arranged with the patients' primary care physician to evaluate the proposals for improvement. The implementation of the proposals and the variation in postintervention glycemic control were assessed. RESULTS: A total of 907 patients (59% men) were included. A total of 782 proposals for intervention were made in 65.8% of the patients reviewed. Of the proposals, 43.5% corresponded to drug discontinuation, 16% to intensification of dosing and 12.6% to exchange for a therapeutic equivalent. Of the consensual proposals, 54.7% were implemented. HbA1c was reduced by 0.2% after the intervention (7.4 vs 7.2%). CONCLUSIONS: Review of the pharmacological treatment of patients with type 2 diabetes mellitus by a pharmacist or pharmacologist facilitates its optimization.

Autophagy, a relevant process for metabolic health and type-2 diabetes / Autofagia, un proceso relevante para la salud y la diabetes tipo 2

Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM. (AU)

La autofagia es un proceso muy activo que juega un papel importante en la diferenciación y remodelación de células y órganos, siendo un sistema crucial para garantizar la salud. Este proceso fisiológico se activa en la inanición y se inhibe en presencia de nutrientes. En esta breve revisión se definen los tres tipos de autofagia: macroautofagia, microautofagia y autofagia mediada por chaperonas, y los diferentes aspectos que controlan la autofagia y su relación con la salud y las enfermedades degenerativas. Como la autofagia depende en gran medida de las proteínas funcionales de autofagia (ATG) que integran el fagóforo, se comenta brevemente el papel clave de algunos genes y epigenes de las ATG. El manuscrito profundiza discutiendo algunos aspectos centrales de la diabetes mellitus tipo 2 (DMT2) y su relación con el proceso de limpieza celular y el mantenimiento de la homeostasis mitocondrial, así como los mecanismos a través de cuales los fármacos antidiabéticos afectan a la autofagia. Se necesitan estudios bien diseñados para dilucidar si la autofagia juega un papel de casualidad o causalidad en el desarrollo de la DMT2. (AU)

Autophagy, a relevant process for metabolic health and type-2 diabetes.

Introduction: Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM.

Introducción: La autofagia es un proceso muy activo que juega un papel importante en la diferenciación y remodelación de células y órganos, siendo un sistema crucial para garantizar la salud. Este proceso fisiológico se activa en la inanición y se inhibe en presencia de nutrientes. En esta breve revisión se definen los tres tipos de autofagia: macroautofagia, microautofagia y autofagia mediada por chaperonas, y los diferentes aspectos que controlan la autofagia y su relación con la salud y las enfermedades degenerativas. Como la autofagia depende en gran medida de las proteínas de autofagia funcional (ATG) que integran el fagóforo, se comenta brevemente el papel clave de algunos genes y epigenes de las ATG. El manuscrito profundiza discutiendo algunos aspectos centrales de la diabetes mellitus de tipo 2 (DMT2) y su relación con el proceso de limpieza celular y el mantenimiento de la homeostasis mitocondrial, así como los mecanismos a través de cuales los fármacos antidiabéticos afectan a la autofagia. Se necesitan estudios bien diseñados para dilucidar si la autofagia juega un papel de casualidad o causalidad en el desarrollo de la DMT2.

Uso de inhibidores de sglt 2 en pacientes con nefropatía diabética / Use of SGLT-2 inhibitors in patients with diabetic nephropathy

El tratamiento antidiabético oral ha sido un reto en el manejo de la diabetes mellitus. Los pacientes con algún grado de enfermedad renal crónica corren serios riesgos de hipoglucemia, sin embargo, los inhibidores del transportador de glucosa SGLT2 suponen un nuevo abordaje terapéutico de la diabetes mellitus tipo 2. Estudios en modelos experimentales de diabetes han demostrado que la inducción de glucosuria revierte la glucotoxicidad, restaura la normoglucemia, y mejora el funcionamiento de la célula beta y la sensibilidad a la insulina. Por lo tanto, se constituyen en una alternativa segura en estos pacientes.

Oral antidiabetic treatment has been a challenge in the management of diabetes mellitus in patients with some degree of chronic kidney disease due to the constant risks of hypoglycemia; however, glucose transporter SGLT2 inhibitors represent a new therapeutic approach to diabetes mellitus. Type 2, studies in experimental models of diabetes have shown thatthe induction of glycosuria reverses glucotoxicity, restores normoglycemia, and improves beta cell function and insulin sensitivity.

Interacciones en el tratamiento antitrombótico e hipoglucemiante / Interactions in antithrombotic and hypoglycemic therapy

Resumen Esta revisión consiste en una puesta al día del tratamiento antiplaquetario y la interacción que presenta con los hipoglucemiantes orales en pacientes diabéticos con cardiopatía isquémica. Re sumimos los principales mecanismos fisiopatológicos que intervienen en el aumento del riesgo cardiovascular en este grupo, los efectos de la combinación entre los hipoglucemiantes orales, sus efectos antitrombóticos y su interacción con los antiplaquetarios y, por último, los trabajos que estudiaron los beneficios de los antiplaque tarios en pacientes diabéticos en diferentes escenarios de la cardiopatía isquémica. Los variados mecanismos de acción implican una mejora del control de la glucemia, del aumento de la biodisponibilidad del óxido nítrico, reducción del estrés oxidativo y, para ciertas moléculas, una inhibición directa de la activación y de la agregación plaquetaria.

Abstract This review is an update on antiplatelet therapy and its interaction with oral hypoglycemic agents in diabetic patients with ischemic heart disease. We summarize the main pathophysiological mechanisms that intervene in diabetic patients and that increase the ischemic risk, the effects of the combination of oral hypoglycemic agents, their antithrombotic ef fects and their interaction with antiplatelet, and finally the studies that demonstrated the benefits of antiplatelet in diabetic patients in different scenarios of ischemic heart disease. The different mechanisms of action involve improved glycemic control, increased bioavailability of nitric oxide, reduced oxidative stress and, for certain mol ecules, direct inhibition of platelet activation and aggregation.

Desenvolvimento e validação de método analítico por CLAE para determinação simultânea de atorvastatina, losartana e metformina em formulações farmacêuticas magistrais

Objetivos: Desenvolver e validar um método analítico para a análise simultânea de atorvastatina (ATO), losartana (LOS) e metformina (MTF) em formulações farmacêuticas magistrais por CLAE. Método: O método foi desenvolvido empregando o cromatógrafo a líquido modelo Dionex® Ultimate 3000, acoplado ao detector de arranjo de diodos (DAD) e a validação se deu conforme compêndios de validação internacional e nacional. Os seguintes parâmetros foram analisados: linearidade, precisão, exatidão, robustez, seletividade, LD e LQ. A separação cromatográfica foi realizada na coluna Sigma-Aldrich® C18, fase móvel MeOH:H2O (78:22 v/v), pH 3,0 e vazão de 0,3 mL-min-1, modo isocrático. As detecções foram realizadas nos comprimentos de onda de 225 nm (LOS), 236 nm (MTF) e 246 nm (ATO). Resultados: O método foi linear, com coeficientes de correlação linear (r)> 0,99 para todos os fármacos, preciso (DPR entre medidas < 2 %), exato (recuperação entre 98-102 %). As variações propostas no estudo de robustez não tiveram influência significativa nos resultados, exceto a coluna cromatográfica. O método foi seletivo, pois os excipientes não interferiram nas análises. A sensibilidade do método foi demonstrada através da determinação teórica dos LD e LQ. Conclusão: Os resultados obtidos sugerem que o método cromatográfico desenvolvido e validado nessa pesquisa poderá ser empregado nas análises de rotina dos laboratórios de controle de qualidade de medicamentos contendo esses fármacos de forma isolada ou combinados em formulações farmacêuticas de uso oral.

SUMMARY Aims: To develop and validate an analytical method for the simultaneous analysis of atorvastatin (ATO), losartan (LOS), and metformin (MTF) in pharmaceutical compounding by HPLC. Method: The method was developed using a liquid chromatograph model Dionex® Ultimate 3000, coupled to a diode array detector (DAD), and validation was carried out according to international and national validation compendiums. The following parameters were analyzed: linearity, precision, accuracy, robustness, selectivity, LD, and LQ. Chromatographic separation was performed on a Sigma-Aldrich® C18 column, mobile phase MeOH:H2O (78:22 v/v), pH 3.0, and flow rate of 0.3 mL-min-1, isocratic mode. Detections were performed at 225 nm (LOS), 236 nm (MTF), and 246 nm (ATO) wavelengths. Results: The method was linear, with linear correlation coefficients (r)> 0.99 for all drugs, precise (DPR between measurements < 2 %), accurate recovery (between 98-102 %). The variations proposed in the robustness study had no significant influence on the results, except for the chromatographic column. The method was selective, as the excipients did not interfere in the analyses. The sensitivity of the method was demonstrated through the theoretical determination of LD and LQ. Conclusion: The results obtained suggest that the chromatographic method developed and validated in this research can be used in the routine analyzes of quality control laboratories of drugs containing these drugs alone or combined in pharmaceutical formulations for oral use.

Executive Summary from Expert consensus on effectiveness and safety of iDPP-4 in the treatment of patients with diabetes and COVID-19.

BACKGROUND: This consensus aims to clarify the role of Dipeptidyl Peptidase-4 inhibitors (iDPP-4) in managing patients with diabetes during the COVID-19 pandemic. MATERIALS AND METHODS: A PubMed bibliographic search was carried out (December 2019-February 2021). Oxford methodology was used for the evaluation of evidence and possible recommendations were established by consensus. RESULTS: Diabetes appears to be an independent factor in COVID-19 disease (evidence 2b). No increased risk of contagion with iDPP-4 is demonstrated (evidence 2b), and its use has been shown to be safe (evidence 2b). The use of this drug may present a specific benefit in reducing mortality, particularly in in-hospital use (evidence 2a), reducing admission to intensive care units (evidence 2b) and the need for mechanical ventilation (evidence 2b). CONCLUSIONS: The use of iDPP-4 appears to be safe in patients with COVID-19, and quality studies are needed to clarify their possible advantages further.

Terapia basada en incretinas para control glucémico de los pacientes hospitalizados con diabetes tipo 2: una revisión sistemática / Incretin-based therapy for glycemic control of hospitalized patients with type 2 diabetes: a systematic review

La terapia basada en incretinas lleva al control glucémico de una manera dependiente de glucosa con un bajo riesgo de hipoglucemia, por lo que resulta atractiva para su uso hospitalario. El objetivo de esta revisión sistemática fue evaluar los beneficios de la terapia basada en incretinas en pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos. Se buscaron estudios publicados hasta agosto de 2021 en las bases de datos PubMed y Scopus. Se seleccionaron los ensayos clínicos que comparaban la terapia basada en incretinas (sola o en combinación con insulina) versus el régimen con insulina. Los resultados de los estudios incluidos mostraron que la terapia basada en incretinas registró un promedio de glucosa sanguínea, un porcentaje de registros dentro de meta terapéutica y un porcentaje de falla al tratamiento similar al manejo con insulina, particularmente en pacientes con hiperglucemia leve a moderada. Además, el tratamiento basado en incretinas se asoció con una menor dosis total de insulina y una menor incidencia de hipoglucemia. En conclusión, la terapia basada en incretinas logró un control glucémico similar al tratamiento con insulina en los pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos, con la ventaja de disminuir el requerimiento insulínico y con menor riesgo de hipoglucemia (AU)

Incretin-based therapy leads to glycemic control in a glucose-dependent manner with a low risk of hypoglycemia, making it appealing for use in the hospital. The aim of this systematic review was to assess the benefits of incretin-based therapy in patients with type 2 diabetes hospitalized outside of the intensive care unit. We searched for studies published up to August 2021 in the PubMed and Scopus databases. Clinical trials comparing incretin-based therapy (alone or in combination with insulin) versus an insulin regimen were selected. The results of the included studies showed that incretin-based therapy showed mean blood glucose values, a percentage of records within the therapeutic target, and a percentage of treatment failure similar to insulin management, particularly in patients with mild to moderate hyperglycemia. Furthermore, incretin-based treatment was associated with a lower total insulin dose and a lower incidence of hypoglycemia. In conclusion, incretin-based therapy achieved glycemic control similar to insulin treatment in patients with type 2 diabetes hospitalized outside the intensive care unit and has the advantages of reducing the insulin requirement and a lower risk of hypoglycemia (AU)

Incretin-based therapy for glycemic control of hospitalized patients with type 2 diabetes: a systematic review.

Incretin-based therapy leads to glycemic control in a glucose-dependent manner with a low risk of hypoglycemia, making it appealing for use in the hospital. The aim of this systematic review was to assess the benefits of incretin-based therapy in patients with type 2 diabetes hospitalized outside of the intensive care unit. We searched for studies published up to August 2021 in the PubMed and Scopus databases. Clinical trials comparing incretin-based therapy (alone or in combination with insulin) versus an insulin regimen were selected. The results of the included studies showed that incretin-based therapy showed mean blood glucose values, a percentage of records within the therapeutic target, and a percentage of treatment failure similar to insulin management, particularly in patients with mild to moderate hyperglycemia. Furthermore, incretin-based treatment was associated with a lower total insulin dose and a lower incidence of hypoglycemia. In conclusion, incretin-based therapy achieved glycemic control similar to insulin treatment in patients with type 2 diabetes hospitalized outside the intensive care unit and has the advantages of reducing the insulin requirement and a lower risk of hypoglycemia.

Desabastecimiento de antidiabéticos y antihipertensivos en el contexto de la crisis por la COVID-19 en Perú

Introducción: Un adecuado abastecimiento de medicamentos en los establecimientos de salud aumentará la posibilidad de un adecuado control de la hipertensión y la diabetes. Objetivo: Determinar el desabastecimiento de antidiabéticos y antihipertensivos a nivel nacional en el contexto de la crisis por COVID-19. Material y métodos: Análisis del "Sistema integrado de suministro de medicamentos e insumos médicos quirúrgicos" (SISMED) entre el 13 de junio y 15 de julio del 2020, de acuerdo a la lista del "Petitorio nacional único de medicamentos de medicamentos esenciales" (PNUME) del Ministerio de Salud. Resultados: Entre el 16 % y 24% de las regiones están totalmente desabastecidos en al menos un antidiabético y 4 % y 96 % en al menos un antihipertensivo. El antidiabético más desabastecido fue la Metformina de 500 mg y los antihipertensivos más desabastecidos fueron Labetalol 5 mg/ml iny, Atenolol 50 mg tab y Carvedilol 6.25 mg tab. El desabastecimiento fue porcentualmente mayor en hospitales y los institutos especializados en comparación con centros y puestos de salud según región geográfica. Conclusiones: Existe un desabastecimiento de antihipertensivos y antidiabéticos en los establecimientos de salud, el cual es heterogéneo en las diferentes regiones del Perú.

Introduction: An adequate supply of medicines in health establishments will increase the possibility of adequate control of hypertension and diabetes. Objective: To determine the supply of antidiabetic and antihypertensive drugs at the national level in the context of the crisis by COVID-19. Material y methods: Analysis of the "Sistema Integrado de Suministro de Medicamentos e Insumos Médicos Quirúrgicos" (SISMED) Database, between June 13th and July 15th, 2020, according to the "National list for medicines of essential medicines" (PNUME) of Ministry of health. Results: Between 16% and 24% of the departments have a total shortage of at least one antidiabetic, and 4% and 96% of at least one antihypertensive. The most depleted antidiabetic was Metformin 500 mg, and the most depleted antihypertensive drugs were Labetalol 5 mg / ml iny, Atenolol 50 mg tab and Carvedilol 6.25 mg tab. The percentage of distribution was higher in hospitals and specialized institutes in comparison with primary health facilities. Conclusions: There is a shortage of antihypertensive and antidiabetic drugs in health centers in Peru.

Desabastecimiento de antidiabéticos y antihipertensivos en el contexto de la etapa inicial de la pandemia por la COVID-19 en Perú / Shortage of antidiabetic and antihypertensive in the context of the initial stage of the COVID-19 pandemic in Peru

Introducción: Un adecuado abastecimiento de medicamentos en los establecimientos de salud aumentará la posibilidad de un adecuado control de la hipertensión y la diabetes. Objetivo: Determinar el desabastecimiento de antidiabéticos y antihipertensivos a nivel nacional en el contexto de la etapa inicial de la pandemia por la COVID-19 en Perú. Material y métodos: Análisis del "Sistema integrado de suministro de medicamentos e insumos médicos quirúrgicos" (SISMED) entre el 13 de junio y 15 de julio del 2020, de acuerdo a la lista del "Petitorio nacional único de medicamentos de medicamentos esenciales" (PNUME) del Ministerio de Salud. Resultados: Entre el 16 % y 24% de las regiones están totalmente desabastecidos en al menos un antidiabético y entre 4 y 96 % en al menos un antihipertensivo. El antidiabético más desabastecido fue la Metformina de 500 mg y los antihipertensivos más desabastecidos fueron Labetalol 5 mg/ml iny, Atenolol 50 mg tab y Carvedilol 6,5 mg tab. El desabastecimiento fue porcentualmente mayor en hospitales y los institutos especializados en comparación con centros y puestos de salud según región geográfica. Conclusiones: Existe un desabastecimiento de antihipertensivos y antidiabéticos en los establecimientos de salud, el cual es heterogéneo en las diferentes regiones del Perú.

Introduction: Adequate drug supply in health facilities will increase the possibility of adequate control of hypertension and diabetes. Objective: To determine the shortage of antidiabetic and antihypertensive drugs at the national level in the context of the initial stage of the COVID-19 pandemic in Peru. Material and methods: Analysis of the "Sistema integrado de suministro de medicamentos e insumos médicos quirúrgicos" (SISMED) between June 13 and July 15, 2020, according to the list of the "Petitorio nacional único de medicamentos de medicamentos esenciales" (PNUME) of the Ministry of Health. Results: Between 16% and 24% of the regions are totally out of stock in at least one antidiabetic and between 4% and 96% in at least one antihypertensive. The most undersupplied antidiabetic was Metformin 500 mg and the most undersupplied antihypertensives were Labetalol 5 mg/ml injection, Atenolol 50 mg tab and Carvedilol 6.5 mg tab. Stock-outs were percentage-wise higher in hospitals and the specialized institutes compared to health centers and health posts according to geographic region. Conclusions: There is a shortage of antihypertensive and antidiabetic drugs in health facilities, which is heterogeneous in the different regions of Peru.

Fármacos para o tratamento do diabetes mellitus tipo 2: interferência no peso corporal e mecanismos envolvidos / Drugs of the treatment of type 2 diabetes mellitus: interference with body weight and mechanisms involved

A quantidade de pessoas obesas vem crescendo significativamente em todo o mundo.Esse fato representa um risco para o aumento do número de portadores de diabetes mellitus tipo 2. A farmacoterapia do diabetes pode alterar o peso corporal, auxiliando tanto na perda como no ganho ponderal. Diante disso, o objetivo do presente trabalho foi revisar os fármacos utilizados no tratamento da diabetes tipo 2 que podem interferir no peso corporal, a fim de auxiliar os profissionais na orientação de indivíduos portadoresda doença. Para tanto, foi realizada uma revisão integrativa nas bases de dados: SciELO, Scholar Google, PubMed, BVS e Portal de Periódicos Capes, a partir de trabalhos publicados entre 2010 e 2019. Observou-se que as biguanidas, os inibidores da α-glicosidade, os análogos de incretinas, os análogos da amilina e os inibidores do cotransportador de sódio/glicose acarretam perda de peso. Por outro lado, as sulfonilureias, as meglitinidas e as glitazonas conferem ganho de peso ao paciente. Sendo assim, a prescrição desses fármacos deve ser feita de maneira individualizada

Obesity has been growing significantly worldwide, representing a risk for the increase of type 2 diabetes mellitus. The pharmacotherapy of diabetes can alter body weight, aiding in weight loss as well as in weight gain. Therefore, the objective of the present study was to review studies on the drugs used in type 2 diabetes that may interfere with body weight, in order to assist professionals in guiding individuals with diabetes. For this, an integrative review was performed in the SciELO, Scholar Google, PubMed, VHL, and Portal of Capes journals databases, considering works published between 2010 and 2019. We observed that biguanides, α-glucosity inhibitors, analogues of incretins, amylin analogues, and sodium / glucose co-transporter inhibitors lead to weight loss. On the other hand, sulphonylureas, meglitinides, and glitazones confer weight gain. Therefore, the prescription of these drugs should be made in an individualized fashion

Antidiabéticos orais no diabetes gestacional: revisão de literatura / Oral antidiabetics in gestational diabetes: literature review

O diabetes mellitus gestacional (DMG) é um distúrbio metabólico por déficit na produção e/ou ação insulínica. Tem relação direta com um constante estado catabólico associado com maior resistência à ação da insulina. Doença de difícil controle, implica risco materno-fetal elevado. O objetivo é estudar a eficácia das drogas antidiabéticas orais sobre o controle glicêmico no DMG e sua segurança quanto aos desfechos gestacionais e perinatais. Trata-se de revisão de literatura descritiva baseada em dados de artigos, livros-texto e guidelines emitidos nos últimos cinco anos. O antidiabético oral pode ser uma boa alternativa no controle do DMG em fase inicial da doença, na presença de distúrbio metabólico e como complemento da terapia com insulina. Entretanto, por causa de sua passagem placentária, há preocupações com seus efeitos fetais e perinatais. Estudos comparativos destacam a metformina no manejo do DMG, considerando principalmente a segurança materno-fetal.(AU)

Gestational diabetes mellitus (GDM) is a metabolic disorder caused by deficit in production and/or insulin action. It is directly related to a constant catabolic state associated with greater resistance to insulin action. Disease difficult to control, implies high maternal-fetal risk. To study the efficacy of oral antidiabetic drugs on glycemic control in GDM and its safety regarding gestational and perinatal outcomes. Descriptive literature review based on data from articles, textbooks and guidelines issued in the last five years. Oral antidiabetic can be a good alternative in the control of GDM in the initial phase of the disease, in the presence of metabolic disorder and as a complement to insulin therapy. However, there are concerns about its placental passage and perinatal effects. Comparative studies highlight metformin in the management of DMG considering mainly maternal-fetal safety.(AU)

Antidiabéticos en Insuficiencia Cardíaca

Resumen: Introducción: La insuficiencia cardíaca se reconoce como una enfermedad sistémica, por lo que se debe hacer un abordaje holístico y no enfocado exclusivamente a la falla cardíaca. La insuficiencia cardíaca se asocia con múltiples comorbilidades, siendo la diabetes mellitus una de las más frecuentes, estas comparten procesos fisiopatológicos con un comportamiento bidireccional, donde la mala evolución de una puede afectar a la otra. Por tanto, al considerar el tratamiento farmacológico de una de ellas, hay que tener en cuenta que el mismo no sea deletéreo para la otra. En los últimos años se requiere que cualquier tratamiento antidiabético tenga un efecto beneficioso o neutro a nivel cardiovascular. Este hecho es el constante desafío clínico al que el médico se enfrenta en estos pacientes. El objetivo de esta revisión es hacer una puesta a punto de la mejor evidencia disponible en el uso de los antidiabéticos en pacientes con insuficiencia cardíaca. Métodos: Se realizó una revisión sistemática de los principales estudios observacionales, ensayos clínicos, revisiones y metaanálisis publicados del uso de antidiabéticos y efecto cardiovascular, hasta diciembre del 2020, utilizando la base de datos de Pubmed y ScienceDirect. Conclusiones: De la revisión realizada se puede concluir que el fármaco de primera línea en pacientes con diabetes e insuficiencia cardíaca es la metformina, compartiendo este primer eslabón con los iSGLT2 (Empagliflozina, Canagliflozina y Dapagliflozina), según la última evidencia disponible, los que han demostrado ser eficaces en la reducción de las hospitalizaciones por insuficiencia cardíaca entre los pacientes con o sin diabetes y muerte cardiovascular, recientes estudios extienden además beneficio a los pacientes que también asocian enfermedad renal crónica.

Abstract: Introduction: Heart failure is recognized as a systemic disease, thus a holistic approach that is not exclusively focused on heart failure should be used. Heart failure is associated with multiple comorbidities, being diabetes mellitus one of the most frequent. These share pathophysiological processes with a bidirectional behavior, where the poor evolution of one can affect the other. Therefore, when considering the pharmacological treatment of one of them, it must be taken into account that it should not be detrimental to the other. In recent years, any antidiabetic treatment is required to have either a beneficial or a neutral effect at the cardiovascular level. This fact is the constant clinical challenge that physicians have to deal with when treating these patients. The objective of this review is to refine the best available evidence on the use of antidiabetic agents in patients with heart failure. Methods: A systematic review of the main observational studies, clinical trials, reviews and meta-analysis published on the use of antidiabetics agents and cardiovascular effect was carried out until December 2020, using Pubmed and ScienceDirect databases. Conclusions: From the review carried out, it can be concluded that the first-line drug for patients with diabetes and heart failure is metformin. This first link is shared with iSGLT2 (Empagliflozin, Canagliflozin and Dapagliflozin), according to the latest available evidence, which have been proven to be effective in reducing hospitalizations for heart failure among patients with or without diabetes and cardiovascular death. Recent studies also extend benefits to patients who are also associated with chronic kidney disease.

Resumo: Introdução: A insuficiência cardíaca é reconhecida como uma doença sistêmica, portanto, uma abordagem holística deve ser feita e não focada exclusivamente na insuficiência cardíaca. A insuficiência cardíaca está associada a múltiplas comorbidades, o diabetes mellitus uma das mais frequentes, pois compartilham processos fisiopatológicos com comportamento bidirecional, onde a má evolução de um pode afetar o outro. Portanto, ao se considerar o tratamento farmacológico de um deles, deve-se levar em consideração que não é prejudicial ao outro. Nos últimos anos, qualquer tratamento antidiabético é necessário para ter um efeito benéfico ou neutro no nível cardiovascular. Esse fato é o constante desafio clínico que o médico enfrenta nesses pacientes. O objetivo desta revisão é fazer uma pesquisa das melhores evidências disponíveis sobre o uso de anti-diabeticos em pacientes com insuficiência cardíaca. Métodos: Foi realizada uma revisão sistemática dos principais estudos observacionais, ensaios clínicos, revisões e metanálises sobre o uso de antidiabéticos e efeito cardiovascular, até dezembro de 2020, nas bases de dados Pubmed e ScienceDirect. Conclusões: A partir da revisão realizada, pode-se concluir que o medicamento de primeira linha em pacientes com diabetes e insuficiência cardíaca é a metformina, compartilhando esta primeira linha com o iSGLT2 (Empagliflozin, Canagliflozin e Dapagliflozin), de acordo com as últimas evidências disponíveis, para aqueles que se mostraram eficazes na redução de hospitalizações por insuficiência cardíaca entre pacientes com ou sem diabetes e morte cardiovascular, estudos recentes também estendem o benefício a pacientes que também associam doença renal crônica.

Mesa 3: Efectos cardiovasculares de fármacos antidiabéticos / Table 3: Cardiovascular effects of anti-diabetic drugs

Los eventos cardiovasculares representan la mayor complicación de la diabetes. La evidencia sugiere que la metformina mejora los resultados cardiovasculares en pacientes con diabetes, especialmente en el United Kingdom Prospective Diabetes Study (UKPDS) y otros estudios posteriores, por distintos mecanismos. Hay pocos estudios de seguridad cardiovascular para sulfonilureas aunque no tendrían un perfil seguro a este nivel. La gliclazida parece ser la de mejor performance de las drogas de este grupo. Algo similar ocurre con las meglitinidas, para las cuales los datos indican que no aumentarían el riesgo pero tampoco mejorarían la incidencia de eventos cardiovasculares. Las tiazolidinedionas son las drogas más cuestionadas, aunque los estudios y metaanálisis son contradictorios no habría dudas que aumentan el riesgo de insuficiencia cardíaca. Los inhibidores de la DPPIV mostraron resultados neutros a excepción de saxagliptina que aumentaría el riesgo de internación por insuficiencia cardíaca. Existen datos convincentes que los inhibidores de los receptores SGLT-2 a nivel renal y los análogos del GLP-1 intestinal tienen efectos positivos a nivel cardiovascular, con algunas diferencias entre los integrantes de esta familia. En cuanto a las insulinas, los estudios sugieren que tanto los análogos lentos como rápidos tendrían un mejor perfil cardiovascular, ligado principalmente a la menor incidencia de hipoglucemias severas, que insulina NPH y regular respectivamente.

Cardiovascular events represent the greatest complication of diabetes. Evidence suggests that metformin improves CV outcomes in patients with diabetes, especially in the United Kingdom Prospective Diabetes Study (UKPDS) and other subsequent studies, by different mechanisms. There are few cardiovascular safety studies for sulfonylureas although they would not have a safe profile at this level. Gliclazide appears to be the best performing drug in this group. Something similar occurs with meglitinides for which the data indicates that they would not increase the risk but neither would they improve the incidence of cardiovascular events. Thiazolidinediones are the most questioned drugs, although the studies and meta-analyzes are contradictory, there would be no doubt that they increase the risk of heart failure. DPPIV inhibitors showed neutral results except for saxagliptin, which would increase the risk of hospitalization for heart failure. There is convincing data that SGLT-2 receptor inhibitors at the renal level and intestinal GLP-1 analogues have positive effects at the cardiovascular level with some differences between the members of these families. Regarding insulins, studies suggest that both slow and fast analogues would have a better cardiovascular profile, mainly linked to the lower incidence of severe hypoglycemia, than NPH and regular insulin, respectively

Prevalence of diabetes mellitus in patients with home enteral nutrition.

BACKGROUND: There are few data available in the literature on the prevalence of diabetes mellitus (DM) in patients with home enteral nutrition (HEN) via tube feeding. The objective was to analyze the prevalence of DM in patients receiving HEN, as well as evaluating the complications, the prescribed antidiabetic treatments and the nutrition regimen selected. DESIGN: This was a retrospective, single-center, observational study reviewing clinical histories. The population consisted of patients over 18 years of age who started HEN by tube between January 2016 and January 2018. Sociodemographic variables were recorded, as well as variables related to HEN. Additional variables were recorded in patients with DM. RESULTS: In the 198 study patients, followed up for a median of 104 days, the prevalence of DM was 31.8%, and patients with DM were older (71.3±11.5 vs. 64.2±15.8; p=0.002) than those without DM. There were no differences between patients with and without DM as regards the prescription of HEN, its route and form of administration, and its complications. One hundred and thirty-two patients (66.7%) died during follow-up. The presence of DM did not increase the risk of death during follow-up (after adjusting for age, gender, and diagnosis). More than 85% of patients with DM received a specific formula for diabetes, and 84.1% of these patients received drug treatment. CONCLUSION: The prevalence of DM was high in patients receiving HEN, most of whom were prescribed specific enteral nutrition formulas. The presence of DM was not associated with greater morbidity and mortality or with differences in HEN regimens or indications.

Diabetes mellitus e insuficiencia cardíaca: nuevas perspectivas en el tratamiento farmacológico / Diabetes and heart failure: new perspectives in pharmacological treatment

La Diabetes Mellitus (DM) y la Insuficiencia Cardíaca (IC) son enfermedades crónicas cuyas prevalencias han ido en aumento y que determinan una mayor mortalidad de los pacientes que las padecen. La relación de ambas enfermedades es conocida como "Miocardiopatía Diabética" (MD). Los eventos fisiopatológicos principales de la MD son el mal control glicémico, el aumento de captación de ácidos grasos por parte de las células cardiacas, la disfunción endotelial y la remodelación cardíaca. Los nuevos tratamientos, se han enfocado en tratar tanto el control glicémico como la remodelación cardíaca. Los principales exponentes de los fármacos antidiabéticos favorables para la IC en pacientes con DM son los inhibidores del cotransportador de Sodio-Glucosa renal SGLT2 (iSGLT2), y los agonistas del receptor de GLP-1 (aGLP-1). Otros fármacos de relevancia son los antagonistas del receptor de mineralocorticoides (aRMC). Se realiza una revisión de la fisiopatología y del manejo actualizado de la IC en pacientes con DM.

Diabetes Mellitus (DM) and Heart Failure (HF) are chronic diseases whose prevalences have risen and which increase patient mortality. The two diseases are inter-related in what is called "Diabetic Cardiomyopathy" (DC). The main pathophysiological characteristics of cardiomyopathy are poor glycemic control, a rise in the capture of fatty acids by cardiac cells, endothelial dysfunction and cardiac remodeling. The principal anti-diabetic medications beneficial for HF in DM patients are renal sodium-glucose cotransporter-2 inhibitors (SGLT2) and GLP-1 receptor agonists (GLP-1RAs). Other relevant medications are mineralocorticoid receptor antagonists (MRA). We review the pathophysiology and current management of HF in diabetic patients.

[Management of hyperglycaemia with non-insulin drugs in adult patients with type 2 diabetes]. / Manejo de la hiperglucemia con fármacos no insulínicos en pacientes adultos con diabetes tipo 2.

Treatment of diabetes mellitus type2 (DM2) includes healthy eating and exercise (150minutes/week) as basic pillars. For pharmacological treatment, metformin is the initial drug except contraindication or intolerance; in case of poor control, 8 therapeutic families are available (6 oral and 2 injectable) as possible combinations. An algorithm and some recommendations for the treatment of DM2 are presented. In secondary cardiovascular prevention, it is recommended to associate an inhibitor of the sodium-glucose cotransporter type 2 (iSGLT2) or a glucagon-like peptide-1 receptor agonist (arGLP1) in patients with obesity. In primary prevention if the patient is obese or overweight metformin should be combined with iSGLT2, arGLP1, or inhibitors of type4 dipeptidylpeptidase (iDPP4). If the patient does not present obesity, iDPP4, iSGLT2 or gliclazide, sulfonylurea, recommended due to its lower tendency to hypoglycaemia, may be used.

Efectos nefrológicos de los SGLT2. ¿Qué sabemos hasta ahora? / Nephrological effects of SGLT2. What do we know so far?

Resumen: La prevalencia de diabetes mellitus tipo 2 ha crecido de manera significativa, longitudinal y continua a lo largo de los años. Se infiere que el número de adultos con nefropatía diabética también aumentará. Por consiguiente, la nefropatía diabética conserva sustancial importancia en la salud global y existe gran necesidad de minimizar la morbilidad de este padecimiento. Los inhibidores del cotransportador de sodio-glucosa 2 (SGLT2) son la clase farmacológica incorporada más recientemente a los recursos terapéuticos de antidiabéticos orales. Su acción se basa en el bloqueo de los cotransportadores SGLT2 sodio-glucosa que se encuentran en la membrana luminal de las células del túbulo contorneado proximal. Reducen las tasas de hiper-glucemia en pacientes con diabetes mellitus tipo 2 al disminuir la reabsorción renal de glucosa, aumentando así la excreción urinaria de glucosa. Se han demostrado reducciones significativas en hemoglobina glucosilada (HbA1c), junto con disminución de glucosa sérica en ayuno y posprandial en pacientes con diabetes mellitus tipo 2. Aunque la eficacia de los inhibidores de SGLT2 se ve afectada por la función renal, se han realizado subanálisis que evidencian que los inhibidores SGLT2, incluso en el contexto de insuficiencia renal grado 3b o 4, tienen efectos neutros en HbA1c, pero mejoran los parámetros bioquímicos y disminuyen el peso. El objetivo de este artículo es revisar la bibliografía disponible en la actualidad de los efectos renales de los inhibidores de SGLT2.

Abstract Prevalence of type 2 diabetes has increased significantly. It is inferred that the number of adults with diabetic nephropathy will also increase. Therefore, diabetic nephropathy will gain importance in global health and there is a need to minimize morbidity associated to this disease. Sodium-glucose transporter type 2 (SGLT2) inhibitors are the latest pharmacologic class of oral antidiabetics. They act upon the inhibition of SGLT2 co-transporters located in the luminal membrane of cells in the proximal convoluted tubule. Significant reductions in glycated haemoglobin levels, along with lower fasting glucose levels have been associated to SGLT2 inhibitors. Efficacy of SGLT2 inhibitors is affected with kidney failure, nonetheless, a subgroup study showed that SGLT2 inhibitors administered in the context of kidney failure (KDIGO stage 3b or 4) have neutral effects over HbA1C levels, but positive effects over other biochemical parameters and weight loss. The objective of this article is to review literature of renal effects of SGLT2 inhibitors.

Observational studies with type 2 diabetes mellitus treatments in Spain: A systematic literature review.

The aim of this systematic literature review (SLR) was to provide an overview of the Spanish research landscape of observational studies conducted with antidiabetic drugs in T2DM patients, published in the last five years, with special focus on the objectives, methodology and main research areas. Twenty-two articles, corresponding to 20 studies, were included in the analysis. Around 82% of the studies employed a longitudinal study design, collected data retrospectively (72.7%), and were based on secondary data use (63.6%). Pharmacotherapeutical groups most frequently studied were insulin (31.8%) and DPP4i (13.6%). Analytic design was employed most in the studies (68.2%), followed by descriptive analysis (22.7%). In the top five of the most studied variables are those related to effectiveness assessed according to glycaemic control (91%), treatment patterns (82%), safety (hypoglycaemia) (59%), the identification of effectiveness predictive factors (45%) and effectiveness according to other control measures such as anthropometric control or cardiovascular risk factors (36%).