Los iSGLT2 en la insuficiencia cardiaca. ¿Sus beneficios pueden extenderse a todo el espectro de la fracción de eyección? / SGLT2i in heart failure: can their benefits be expanded across the entire spectrum of ejection fraction?

La publicación del estudio EMPEROR-Preserved y la extensión del beneficio cardiovascular de los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) a pacientes con insuficiencia cardiaca IC y fracción de eyección (FE)> 40% supone un importante hito en el tratamiento de la IC con FE conservada (IC-FEc). A raíz de estos resultados, en febrero de 2022 la Food and Drug Administration estadounidense aprobó el uso de la empagliflozina para el tratamiento de pacientes con IC independientemente de la FE. Sin embargo, un análisis más detallado del estudio EMPEROR-Preserved genera ciertas dudas en relación con la banda de FE más alta (> 60%). Este grupo de pacientes presenta una gran heterogeneidad y probablemente no se pueda considerar un único fenotipo para fines terapéuticos y de abordaje clínico. Además, la FE es un parámetro continuo. Por ello, no parece que una diferenciación basada en puntos de corte matemáticos concuerde con la evidencia más reciente, que apunta precisamente a un cambio más gradual en cuanto a mecanismos subyacentes, etiologías y respuesta al tratamiento a lo largo del espectro de la FE. Un mejor conocimiento de los mecanismos fisiopatológicos es fundamental para establecer nuevas dianas terapéuticas, interpretar los resultados de los ensayos clínicos y desarrollar tratamientos dirigidos y eficaces (AU)

The publication of the EMPEROR-Preserved trial and data on the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with ejection fraction (EF)> 40% represent a significant step forward in the treatment of HF with preserved EF. Given these results, in February 2022 the US Food and Drug Administration approved the use of empaglifozin in adults with HF with reduced or preserved EF. However, more detailed analysis of the EMPEROR-Preserved trial led to doubts about the effect of empagliflozin in patients with an EF of> 60% this patient group is widely heterogeneous and, probably, a single phenotype cannot be considered in treatment goals or the clinical approach. Moreover, EF occurs on a continuum and classifications of HF according to arbitrary cut-points in EF do not appear consistent with recent evidence, which points to a gradual shift and considerable overlap in underlying mechanisms, phenotypes and treatment response over the spectrum of EF. Enhanced knowledge of pathophysiological mechanisms is essential to establish new therapeutic targets, interpret the results of clinical trials, and develop targeted and effective therapies (AU)

SGLT2i in heart failure: can their benefits be expanded across the entire spectrum of ejection fraction?

The publication of the EMPEROR-Preserved trial and data on the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure (HF) with ejection fraction (EF)> 40% represent a significant step forward in the treatment of HF with preserved EF. Given these results, in February 2022 the US Food and Drug Administration approved the use of empaglifozin in adults with HF with reduced or preserved EF. However, more detailed analysis of the EMPEROR-Preserved trial led to doubts about the effect of empagliflozin in patients with an EF of> 60% this patient group is widely heterogeneous and, probably, a single phenotype cannot be considered in treatment goals or the clinical approach. Moreover, EF occurs on a continuum and classifications of HF according to arbitrary cut-points in EF do not appear consistent with recent evidence, which points to a gradual shift and considerable overlap in underlying mechanisms, phenotypes and treatment response over the spectrum of EF. Enhanced knowledge of pathophysiological mechanisms is essential to establish new therapeutic targets, interpret the results of clinical trials, and develop targeted and effective therapies.

Manejo de perfiles de pacientes con diabetes mellitus tipo2 en la práctica clínica de la atención primaria en España: Programa CONTROVERTI2 / Management of patient profiles with type2 diabetes mellitus in Primary Care in Spain: CONTROVERTI2 Program

Objetivo: Identificar controversias existentes en el manejo habitual de los pacientes con diabetes mellitus tipo2 (DM2) y contrastarlas con la última evidencia científica y guías clínicas, con el fin de optimizar y homogeneizar el tratamiento de los pacientes con DM2 en la atención primaria (AP) en España. Material y métodos: 240 médicos de familia respondieron a un cuestionario online sobre el manejo de 6 perfiles de pacientes con DM2 de complejidad creciente. Resultados: Los factores clínicos más influyentes en la elección del tratamiento antihiperglucémico son una HbA1c >10% y la presencia de enfermedad cardiovascular (ECV), aunque en el paciente evolucionado cobran más relevancia la tasa de filtrado glomerular estimada y el riesgo de hipoglucemia. En el paciente recién diagnosticado con HbA1c>9% se sigue iniciando el tratamiento con monoterapia (24%). En el paciente no controlado con metformina suelen añadirse inhibidores de la dipeptidil peptidasa4 (iDPP4, 54%) seguido de inhibidores del cotransportador sodio-glucosa tipo2 (iSGLT2, 39%). Los agonistas del receptor del péptido similar al glucagón tipo1 (arGLP1) se asocian principalmente al paciente con DM2 obeso. En el paciente no controlado con metformina+sulfonilurea (SU) se prefiere sustituir la SU a añadir un tercer agente antihiperglucémico al tratamiento (77% vs. 23%). Conclusiones: Todavía persiste en AP un enfoque del tratamiento de la DM2 centrado en la reducción de la HbA1c y en la seguridad de los tratamientos. Por ello, los iDPP4 son fármacos ampliamente utilizados. Los iSGLT2 se reservan habitualmente para pacientes con DM2 y ECV y los arGLP1 para pacientes con DM2 obesos, siendo su uso muy limitado (AU)

Aim: To identify existing controversies in the routine management of patients with T2D and to contrast them with the latest scientific evidence and clinical guidelines, in order to help optimize and homogenize the treatment of patients with T2D in Primary Care (PC) in Spain. Material and methods: 240 family doctors responded to an online questionnaire about the management of 6 patient profiles with T2D of increasing complexity. Results: The main drivers for the antihyperglycemic treatment choice are an HbA1c>10% and the presence of cardiovascular disease (CVD), although in evolved patients, the estimated glomerular filtration rate and the risk of hypoglycemia become more relevant. In newly diagnosed patients with an HbA1c>9%, treatment is still initiated with monotherapy (24%). In patients not controlled with metformin, dipeptidyl peptidase 4 inhibitors (DPP4-I, 54%) or sodium-glucose cotransporter 2 inhibitors (SGLT2-I, 39%) are usually added. On the other hand, type1 glucagon-like peptide receptor agonists (GLP1-RA) are mainly associated with obese patients with T2D. In patients not controlled with metformin+sulfonylurea (SU), SU replacement is preferred to adding a third antihyperglycemic agent to background therapy (77% vs. 23%). Conclusions: T2D treatment in PC is still focused on HbA1c reduction and treatment safety. Thus, DPP4-I are widely used. SGLT2-I are usually preferred for patients with T2D and CVD and GLP1-RA for patients with T2D and obesity, although their use in PC is low (AU)

[Management of patient profiles with type2 diabetes mellitus in Primary Care in Spain: CONTROVERTI2 Program]. / Manejo de perfiles de pacientes con diabetes mellitus tipo2 en la práctica clínica de la atención primaria en España: Programa CONTROVERTI2.

AIM: To identify existing controversies in the routine management of patients with T2D and to contrast them with the latest scientific evidence and clinical guidelines, in order to help optimize and homogenize the treatment of patients with T2D in Primary Care (PC) in Spain. MATERIAL AND METHODS: 240 family doctors responded to an online questionnaire about the management of 6 patient profiles with T2D of increasing complexity. RESULTS: The main drivers for the antihyperglycemic treatment choice are an HbA1c>10% and the presence of cardiovascular disease (CVD), although in evolved patients, the estimated glomerular filtration rate and the risk of hypoglycemia become more relevant. In newly diagnosed patients with an HbA1c>9%, treatment is still initiated with monotherapy (24%). In patients not controlled with metformin, dipeptidyl peptidase 4 inhibitors (DPP4-I, 54%) or sodium-glucose cotransporter 2 inhibitors (SGLT2-I, 39%) are usually added. On the other hand, type1 glucagon-like peptide receptor agonists (GLP1-RA) are mainly associated with obese patients with T2D. In patients not controlled with metformin+sulfonylurea (SU), SU replacement is preferred to adding a third antihyperglycemic agent to background therapy (77% vs. 23%). CONCLUSIONS: T2D treatment in PC is still focused on HbA1c reduction and treatment safety. Thus, DPP4-I are widely used. SGLT2-I are usually preferred for patients with T2D and CVD and GLP1-RA for patients with T2D and obesity, although their use in PC is low.

Efficacy and safety of metformin and sodium-glucose co-transporter-2 inhibitors in adults with type1 diabetes: A systematic review and network meta-analysis. / Eficacia y seguridad de la metformina y de los inhibidores del cotransportador-2 de sodio-glucosa en adultos con diabetes tipo 1: una revisión sistemática y metaanálisis en red.

AIM: To compare the efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors and metformin in adults with type1 diabetes mellitus (T1DM). METHODS: Randomized clinical trials until February 2019, designed to assess the efficacy and safety of SGLT2 inhibitors/metformin in adults with T1DM, were searched on PubMed, EMBASE, the Cochrane Library, and Web of Science. Safety and efficacy data were synthesized using Bayesian network meta-analyses. RESULTS: Twenty eligible studies with 5868 participants were included in network meta-analysis. SGLT2 inhibitors provided greater reductions in HbA1c than placebo (weighted mean difference [WMD] -0.40; 95% confidence interval [CI] -0.47, -0.32) and metformin (WMD: -0.32; 95%CI: -0.47, -0.14). Both SGLT2 inhibitors and metformin promoted greater reductions in body weight than placebo. SGLT2 inhibitors caused greater reductions in body weight than metformin (WMD: -1.54; 95%CI: -2.93, -0.09). Both SGLT2 inhibitors and metformin provided greater reductions in total insulin dose than placebo, while no difference between metformin and SGLT2 inhibitors was found. No difference in severe hypoglycemia was found between SGLT2 inhibitors and metformin. SGLT2 inhibitors induced a higher risk for diabetic ketoacidosis (DKA) than metformin/placebo. CONCLUSION: SGLT2 inhibitors provided greater reductions in HbA1c and body weight than metformin/placebo. Both SGLT2 inhibitors and metformin induced greater reductions in total insulin dosage than placebo, with no significant differences observed between SGLT2 inhibitors and metformin. SGLT2 inhibitors induced a higher risk for DKA than metformin/placebo.

Positioning of sodium-glucose cotransporter-2 inhibitors in national and international guidelines. / Posicionamiento en guías nacionales e internacionales de los inhibidores del cotransportador sodio-glucosa tipo 2.

Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) selectively and reversibly inhibit sodium-glucose cotransporter-2 (SGLT2), promoting renal glucose excretion and reducing plasma glycaemia. By increasing renal glucose excretion, these drugs favour a negative energy balance, leading to weight loss. Their glucoselowering effect is independent of insulin. Although these drugs have only recently been developed, they have been included in all the main national and international guidelines since 2014. The present review summarises the most important recommendations on the use of SGLT2 in patients with DM2 contained in the most recently published guidelines and consensus statements.