Rupa Ahluwalia

Emerging role of insulin with incretin therapies for management of type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a progressive disease warranting intensification of treatment, as beta-cell function declines over time. Current treatment algorithms recommend metformin as the first-line agent, while advocating the addition of either basal-bolus or premixed insulin as the final level of intervention. Incretin therapy, including incretin mimetics or enhancers, are the latest group of drugs available for treatment of T2DM. These agents act through the incretin axis, are currently recommended as add-on agents either as second-or third-line treatment, without concurrent use of insulin. Given the novel role of incretin therapy in terms of reducing postprandial hyperglycemia, and favorable effects on weight with reduced incidence of hypoglycemia, we explore alternative options for incretin therapy in T2DM management. Furthermore, as some evidence alludes to incretins potentially increasing betacell mass and altering disease progression, we propose introducing these agents earlier in the treatment algorithm. In addition, we suggest the concurrent use of incretins with insulin, given the favorable effects especially in relation to weight gain.

Safety and tolerability of glucagon-like peptide-1 receptor agonists in the treatment of type 2 diabetes

Conventional pharmacotherapies for type 2 diabetes effectively lower blood glucose levels but are associated with side effects that preclude their optimal use or raise safety concerns. Novel treatments based on the endogenous hormone glucagon-like peptide-1 (GLP-1) may overcome some of these obstacles. The GLP-1 receptor agonists, exenatide and liraglutide, have a lower risk of hypoglycaemia than some conventional agents and can provide significant weight loss. Although they can cause gastrointestinal symptoms, effects are transient and can be reduced by gradual dose escalation. No cardiac safety issues have been reported and animal studies suggest that they may confer cardiovascular benefits. Pancreatitis has occurred among patients receiving GLP-1 receptor agonists, but it is unclear whether this is drug-related or due to the increased risk of pancreatitis in type 2 diabetes. Despite findings in rodents that GLP-1 receptor activation of thyroid C-cells results in calcitonin release and C-cell pathology, such effects have not been seen with longterm exposure in humans. Immunogenicity does not appear to be a safety concern. In summary, currently available data indicate that GLP-1 receptor agonists provide an effective and generally well tolerated therapeutic option for the management of type 2 diabetes. Br J Diabetes Vasc Dis 2012;12:6-16

Tratamiento de la diabetes mellitus tipo 2 a partir de las directrices de práctica clínica

Resumen En la epoca actual, estamos asistiendo a un aumento sin precedentes de la incidencia de la diabetes tipo 2 relacionado con un incremento de los grados de adiposidad. Ademas, la naturaleza compleja de la enfermedad con pacientes mucho mas jovenes que antano hace que la prescripcion del tratamiento sea una tarea dificil para los medicos contemporaneos. El advenimiento de farmacos basados en las incretinas ha convertido el tratamiento en una actividad fascinante, pero tambien es necesario el uso prudente de estos preparados debido a los costes mas altos de prescripcion y al perfil limitado de datos de tolerabilidad. Al mismo tiempo, un numero de pruebas cada vez mayor no solo respalda una estrategia de tratamiento precoz, sino que tambien aconseja precaucion en la obtencion de un control glucemico estricto con excesiva celeridad en determinados grupos de pacientes. En este laberinto terapeutico, las guias clinicas son utiles porque acercan las mejores evidencias disponibles a la practica clinica. En este capitulo, abordamos las guias clinicas mas recientes para el tratamiento de la diabetes tipo 2 basadas en las recomendaciones de la American Diabetes Association, European Association for the Study of Diabetes y National Institute of Clinical Excellence (Reino Unido). Al mismo tiempo, destacamos las limitaciones de estas guias porque no proporcionan opciones para todos los ambitos de la “vida real”. Aunque son utiles para acercar las evidencias a la practica clinica, en ultimo termino, es responsabilidad del medico racionalizar el tratamiento en funcion de las necesidades del paciente individual. A la vez, en particular en la epoca actual de la cultura de las “retribuciones por rendimiento” en asistencia sanitaria, tambien es decisivo obtener resultados significativos en salud que repercutan en la vida del paciente, con el objetivo de proporcionar unos cuidados estandarizados para cada uno de los pacientes con diabetes.