RESUMEN
Over recent decades, an improved understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) and glucose regulation has led to innovative research and new treatment paradigms. The discovery of the gut peptide glucagon-like peptide-1 (GLP-1) and its role in glucose regulation paved the way for the class of GLP-1 receptor agonist compounds, or GLP-1RAs. The long-acting GLP-1RAs (dulaglutide, exenatide extended-release, liraglutide, semaglutide [injectable and oral]) are classified as such based on a minimum 24-hour duration of clinically relevant effects after administration. In phase 3 clinical trial programs of long-acting GLP-1RAs, A1C typically was reduced in the range of 1% to 1.5%, with reductions close to 2% in some studies. GLP-1RAs when used alone (without sulfonylureas or insulin) have a low risk of hypoglycemia because, like endogenous GLP-1, their insulinotropic effects are glucose-dependent. In addition to local actions in the gastrointestinal (GI) tract, GLP-1RAs stimulate receptors in the central nervous system to increase satiety, resulting in weight loss. All long-acting GLP-1RAs have, at minimum, been shown to be safe and not increase cardiovascular (CV) risk and most (liraglutide, semaglutide injectable, dulaglutide, albiglutide) have been shown in CV outcomes trials (CVOTs) to significantly reduce the risk of major cardiac adverse events. The class has good tolerability overall, with generally transient GI adverse events being most common. The weekly injectable agents offer scheduling convenience and may promote treatment adherence. One long-acting GLP-1RA is available as an oral daily tablet, which may be preferable for some patients and providers.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida/administración & dosificación , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/análogos & derivados , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Liraglutida/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Administración Oral , Preparaciones de Acción Retardada , Exenatida/farmacología , Péptido 1 Similar al Glucagón/fisiología , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/farmacología , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Fragmentos Fc de Inmunoglobulinas/farmacología , Inyecciones , Liraglutida/farmacología , Proteínas Recombinantes de Fusión/farmacología , Respuesta de Saciedad/efectos de los fármacos , Pérdida de Peso/efectos de los fármacosRESUMEN
Over recent decades, an improved understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) and glucose regulation has led to innovative research and new treatment paradigms. The discovery of the gut peptide glucagon-like peptide-1 (GLP-1) and its role in glucose regulation paved the way for the class of GLP-1 receptor agonist compounds, or GLP-1RAs. The long-acting GLP-1RAs (dulaglutide, exenatide extended-release, liraglutide, semaglutide [injectable and oral]) are classified as such based on a minimum 24-hour duration of clinically relevant effects after administration. In phase 3 clinical trial programs of long-acting GLP-1RAs, A1C typically was reduced in the range of 1% to 1.5%, with reductions close to 2% in some studies. GLP-1RAs when used alone (without sulfonylureas or insulin) have a low risk of hypoglycemia because, like endogenous GLP-1, their insulinotropic effects are glucose-dependent. In addition to local actions in the gastrointestinal (GI) tract, GLP-1RAs stimulate receptors in the central nervous system to increase satiety, resulting in weight loss. All long-acting GLP-1RAs have, at minimum, been shown to be safe and not increase cardiovascular (CV) risk and most (liraglutide, semaglutide injectable, dulaglutide, albiglutide) have been shown in CV outcomes trials (CVOTs) to significantly reduce the risk of major cardiac adverse events. The class has good tolerability overall, with generally transient GI adverse events being most common. The weekly injectable agents offer scheduling convenience and may promote treatment adherence. One long-acting GLP-1RA is available as an oral daily tablet, which may be preferable for some patients and providers.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Liraglutida/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Administración Oral , Preparaciones de Acción Retardada , Diabetes Mellitus Tipo 2/metabolismo , Péptido 1 Similar al Glucagón/farmacología , Péptido 1 Similar al Glucagón/fisiología , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Glucosa/metabolismo , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/farmacología , Liraglutida/administración & dosificación , Liraglutida/farmacología , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/farmacología , Seguridad , Resultado del TratamientoRESUMEN
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality for patients with diabetes. The latest guidelines from the American Diabetes Association include new information on hypertension, lipid management, heart failure, and coronary heart disease. This year, for the first time, the cardiovascular disease and risk management section was endorsed by the American College of Cardiology. Primary and secondary prevention of ASCVD is a critical element of the primary care visit for patients with diabetes. This article provides key highlights that are important for busy clinicians.