Liraglutide in a real-world setting: Joint modeling of metabolic response, prediction of efficacy, and cardiovascular risk / Liraglutida en vida real: modelización conjunta de la respuesta metabólica, predicción de eficacia y riesgo cardiovascular

Introduction and objectives: The worldwide prevalence of type 2 diabetes mellitus increases in parallel to that of obesity. Liraglutide (LRG), a glucagon-like peptide-1 receptor agonist, can reduce body weight. This study assessed the metabolic efficacy of LRG in real-world clinical practice. Methods: An observational, retrospective cohort study including patients treated with LRG for at least one year (187 patients). Anthropometric and metabolic variables, a composite endpoint, factors predicting response to LRG, and cardiovascular risk over time were assessed. A linear mixed-effects model with a bivariate structure was constructed to investigate the time-dependent relationship between weight and HbA1c values. Results: HbA1c levels and weight significantly decreased in the first 12 weeks, and the decrease persisted at 12 and 24 months in all subgroups studied. Mean weight and HbA1c decreases after 24 months were 8.5kg and 1.7% respectively. HbA1c values <7% were achieved by 42% of patients at 12 months and by 40% at 24 months. Treatment with LRG allowed for reduction in insulin dose. No serious adverse events were noted. Cardiovascular risk decreased from high to moderate-low. Conclusions: Under standard clinical practice conditions, LRG achieved a better metabolic response than seen in clinical trials. Efficacy at 12 weeks of treatment is a good predictor of response. LRG allows for delaying or reducing insulin dose by improving both weight and glucose control. Cardiovascular risk improved

Introducción y objetivos: La prevalencia mundial de diabetes mellitus tipo 2 aumenta junto a la de la obesidad. Liraglutida (LRG), un agonista del receptor del péptido similar al GLP1, es un fármaco antidiabético capaz de reducir peso. Evaluamos en práctica clínica de vida real su eficacia metabólica. Método: Estudio de cohorte observacional retrospectivo. Se incluyeron los pacientes tratados al menos durante un año con LRG (187 pacientes). Evaluamos variables antropométricas, metabólicas, objetivos combinados, factores predictivos de respuesta y evolución del riesgo cardiovascular. Se construyó un modelo de efectos mixtos lineales de estructura bivariante para investigar la relación tiempo-dependiente entre el peso y los valores de HbA1c. Resultados: Descenso significativo de los valores de HbA1c y peso en las primeras 12 semanas de tratamiento, mantenido a los 12 y 24 meses, en todos los subgrupos estudiados. Reducción media de peso y HbA1c tras 24 meses de tratamiento de 8,5 kg y 1,7%. El valor de HbA1c fue <7% en 42% de pacientes a los 12 meses, 40% a los 24 meses. El tratamiento con LRG permitió reducir la dosis de insulina. No registramos eventos adversos graves. El riesgo cardiovascular mejoró. Conclusiones: Bajo condiciones de práctica clínica habitual la respuesta metabólica a LRG resultó mejor que la observada en ensayos clínicos. La eficacia a las 12 semanas de tratamiento es un buen predictor de respuesta. LRG permite retrasar o reducir la insulinoterapia. Los pacientes mejoraron su riesgo cardiovascular

Relationship between glycated hemoglobin and glucose concentrations in the adult Galician population: selection of optimal glycated hemoglobin cut-off points as a diagnostic tool of diabetes mellitus

Aims/hypothesis To analyze the relationship between glucose and glycated hemoglobin (HbA1c) in the adult Galician population, evaluate the use of HbA1c for the screening and diagnosis of diabetes, and calculate the diagnostic threshold required for this purpose. Methods We analyzed data on 2848 subjects (aged 18-85 years) drawn from a study undertaken in 2004 to assess the prevalence of diabetes in Galicia. For study purposes, diabetes was defined using the criteria recommended in 2002. Participants were classified into four glucose-based groups. The relationship between glucose and HbA1c was described using linear regression models, generalized additive models and Spearman's correlation. Diagnostic capacity was assessed, and optimal HbA1c cut-off points were calculated as a diabetes marker using the receiver operating characteristic curve. Results Prevalence of pre-diabetes, unknown diabetes and known diabetes was 20.86, 3.37 and 4.39%, respectively. The correlations between HbA1c and fasting glucose were higher than those obtained for HbA1c and glycemia at 2h of the oral glucose overload (0.344 and 0.270, respectively). Taking glucose levels as the gold standard, a greater discriminatory capacity was obtained for HbA1c (area under de cruve: 0.839, 95% confidence intervals: 0.788-0.890). Based on the study criteria, the optimal minimum and maximum HbA1c values were 5.9% and 6.7%, respectively. Conclusions/interpretationHbA1c did not prove superior to glycemia for diagnosis of diabetes in the adult Galician population, and cannot therefore be used to replace the oral glucose tolerance test for screening and diagnosis purposes. Indeed, determination of glucose is essential to verify the diagnosis in the majority of cases (AU)

Objetivos/hipótesis: Analizar la relación entre la glucosa y la hemoglobina glucosilada (HbA1c)en la población gallega adulta, evaluar el uso de la HbA1c para cribado y diagnóstico de la diabetes y calcular el umbral diagnóstico necesario para este fin. Métodos: Se analizaron datos de 2.848 sujetos (de 18---85 años de edad) procedentes de un estudio emprendido en 2004 para valorar la prevalencia de diabetes en Galicia. A efectos del estudio, se definió la diabetes de acuerdo con los criterios recomendados en 2002. Se clasificó a los participantes en cuatro grupos en función de los valores de glucosa. Se describió la relación entre glucosa y HbA1c mediante modelos de regresión lineal, modelos aditivos generalizados yl a correlación de Spearman. Se valoró la capacidad diagnóstica y se calcularon los puntos de corte óptimos de la HbA1c como marcador de la diabetes empleando la curva de características operativas del receptor. Resultados: Las tasas de prevalencia de prediabetes, diabetes desconocida y diabetes conocidas eran del 10,86, 3,37 y 4,39%, respectivamente. Las correlaciones entre la HbA1c y la glucemia en ayunas eran mayores que las obtenidas entre la HbA1c y la glucemia en ayunas dos horas después de la sobrecarga oral de glucosa (0,344 y 0,270, respectivamente). Tomando los valores de glucosa como referencia, se obtuvo una mayor capacidad discriminatoria para la HbA1c (área bajo la curva: 0,839, intervalos de confianza del 95%: 0,788---0,890). Basándose en los criterios del estudio, los valores óptimos mínimos de la HbA1c eran del 5,9 y el 6,7%, respectivamente. Conclusiones/interpretación: La HbA1c no fue superior a la glucemia para el diagnóstico de la diabetes en la población gallega adulta, por lo que no puede utilizarse en lugar de la prueba de tolerancia oral a la glucosa con fines de cribado y diagnóstico. De hecho, la determinación de la glucosa es esencial para confirmar el diagnóstico en la mayoría de los casos (AU)

Relationship between glycated hemoglobin and glucose concentrations in the adult Galician population: selection of optimal glycated hemoglobin cut-off points as a diagnostic tool of diabetes mellitus.

AIMS/HYPOTHESIS: To analyze the relationship between glucose and glycated hemoglobin (HbA(1c)) in the adult Galician population, evaluate the use of HbA(1c) for the screening and diagnosis of diabetes, and calculate the diagnostic threshold required for this purpose. METHODS: We analyzed data on 2848 subjects (aged 18-85 years) drawn from a study undertaken in 2004 to assess the prevalence of diabetes in Galicia. For study purposes, diabetes was defined using the criteria recommended in 2002. Participants were classified into four glucose-based groups. The relationship between glucose and HbA(1c) was described using linear regression models, generalized additive models and Spearman's correlation. Diagnostic capacity was assessed, and optimal HbA(1c) cut-off points were calculated as a diabetes marker using the receiver operating characteristic curve. RESULTS: Prevalence of pre-diabetes, unknown diabetes and known diabetes was 20.86, 3.37 and 4.39%, respectively. The correlations between HbA(1c) and fasting glucose were higher than those obtained for HbA(1c) and glycemia at 2h of the oral glucose overload (0.344 and 0.270, respectively). Taking glucose levels as the gold standard, a greater discriminatory capacity was obtained for HbA(1c) (area under de cruve: 0.839, 95% confidence intervals: 0.788-0.890). Based on the study criteria, the optimal minimum and maximum HbA(1c) values were 5.9% and 6.7%, respectively. CONCLUSIONS/INTERPRETATION: HbA(1c) did not prove superior to glycemia for diagnosis of diabetes in the adult Galician population, and cannot therefore be used to replace the oral glucose tolerance test for screening and diagnosis purposes. Indeed, determination of glucose is essential to verify the diagnosis in the majority of cases.