RESUMEN
This study evaluates the cardiovascular risk and safety of a dual peroxisome proliferator-activated receptor alpha and gamma (PPARα&γ), aleglitazar, for the management of type 2 diabetes mellitus. Studies were identified after a literature search in electronic databases and included in the meta-analysis according to eligibility criteria. Meta-analyses of mean differences in the changes from the baseline or odds ratios of selected indices between the aleglitazar- and the placebo/comparator-treated participants were performed. Seven studies {11,832 individuals; age 59.3 years [95% confidence interval (CI) 56.4-61.9]; body mass index 30.8 kg/m [95% CI 30.1-31.7]; sex, 54% males [44-64]} were included. In comparison with the placebo or pioglitazone, the aleglitazar treatment significantly improved %HbA1c, high-density lipoprotein-cholesterol (HDL-chol), and triglycerides. Aleglitazar also significantly decreased fasting plasma glucose and apolipoprotein B compared with the placebo. However, compared with the placebo or pioglitazone, aleglitazar significantly increased serum creatinine levels and significantly decreased the estimated glomerular filtration rate. In addition, the aleglitazar treatment was associated with a significantly increased body weight. Incidence of hypoglycemia, gastrointestinal hemorrhage, bone fractures, heart failure, cardiovascular death, and malignancy was higher in the aleglitazar group. Despite efficacy in glycemic and lipidic control, the aleglitazar treatment was associated with a poor safety profile.
Asunto(s)
Glucemia/efectos de los fármacos , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Oxazoles/uso terapéutico , PPAR alfa/agonistas , PPAR gamma/agonistas , Tiofenos/uso terapéutico , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Incidencia , Lípidos/sangre , Masculino , Persona de Mediana Edad , Oxazoles/efectos adversos , Medición de Riesgo , Factores de Riesgo , Tiofenos/efectos adversos , Resultado del Tratamiento , Aumento de Peso/efectos de los fármacosRESUMEN
The peptide apelin is expressed in the pulmonary vasculature and is involved in the pathogenesis of many cardiovascular diseases. It has a biphasic role in the regulation of vasomotor tone related to the vascular endothelium. In this study, we induced acute pulmonary embolism (APE) in dogs with autologous blood clots to assess the effect of apelin on pulmonary and systemic circulation in the acute phase of APE. The expression of apelin mRNA was found to be upregulated in the lung tissue in the early several hours after APE induction and decreased at 24 h. The expression of apelin protein in the pulmonary arteries did not change within 24 h after APE, but significantly increased in the bronchial epithelial cells as early as 1h and decreased at 24 h. In normal anesthetized dogs, intravenous bolus administration of apelin significantly reduced the mean arterial pressure (MAP), but did not significantly affect the mean pulmonary arterial pressure (MPAP). In the dogs with APE, apelin decreased MPAP, whereas its impact on MAP was not significantly different from that in the control group. Taken together, the level of endogenous apelin did not change significantly in the pulmonary arterial wall, whereas its expression in the bronchial epithelium was upregulated in the early stage of APE. The effect of exogenous apelin on vasomotor tone was complicated: it resulted in differential changes in the pulmonary and systemic arterial pressures under different physiological and pathological conditions.