RESUMEN
Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical response as once-daily monotherapy in patients with moderate to severe RA, also in combination with methotrexate (MTX), who had an inadequate response to MTX. The findings from studies of this new JAK inhibitor have shown that, both in monotherapy as well as in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it has efficacy, safety and tolerability in RA patients.
Asunto(s)
Adamantano/análogos & derivados , Artritis Reumatoide/tratamiento farmacológico , Niacinamida/análogos & derivados , Adamantano/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Quinasas Janus/antagonistas & inhibidores , Niacinamida/uso terapéutico , Resultado del TratamientoAsunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Adamantano/análogos & derivados , Adamantano/uso terapéutico , Compuestos de Bencidrilo/uso terapéutico , Glucemia/efectos de los fármacos , Canagliflozina/uso terapéutico , Ensayos Clínicos como Asunto , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Dipéptidos/uso terapéutico , Quimioterapia Combinada , Glucósidos/uso terapéutico , Hemoglobina Glucada/efectos de los fármacos , Glicósidos/uso terapéutico , Humanos , Hipoglucemia/inducido químicamente , Insulina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: This analysis compared the efficacy and safety of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, dapagliflozin, and the dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin, both added on to metformin. MATERIALS AND METHODS: This was a post-hoc analysis from a double-blind, randomized, 24-week clinical trial (NCT01606007) of patients with type 2 diabetes (T2D) inadequately controlled with metformin. We compared the dapagliflozin 10 mg (n = 179) and saxagliptin 5 mg (n = 176) treatment arms. RESULTS: Dapagliflozin showed significantly greater mean reductions versus saxagliptin in HbA1c (difference versus saxagliptin [95% CI]: -0.32% [-0.54, -0.10]; p < 0.005), fasting plasma glucose (-0.98 [-1.42, -0.54] mmol/L; p < 0.0001), body weight (-2.39 [-3.08, -1.71] kg; p < 0.0001) and systolic blood pressure (SBP) (-3.89 [-6.15, -1.63] mmHg; p < 0.001). More dapagliflozintreated than saxagliptin-treated patients achieved the composite endpoint of HbA1c reduction ≥ 0.5%, weight loss ≥ 2 kg, SBP reduction ≥ 2 mmHg and no major/minor hypoglycemia (24% versus 7%). No major events of hypoglycemia were reported. More patients on dapagliflozin (6%) versus saxagliptin (0.6%) experienced genital infections. CONCLUSION: Dapagliflozin demonstrated greater glycemic efficacy than saxagliptin with additional benefits on weight and SBP, and the safety profile was consistent with previous studies.
Asunto(s)
Adamantano/análogos & derivados , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Transportador 2 de Sodio-Glucosa/uso terapéutico , Adamantano/efectos adversos , Adamantano/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Dipéptidos/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Método Doble Ciego , Quimioterapia Combinada/métodos , Femenino , Glucósidos/efectos adversos , Hemoglobina Glucada/efectos de los fármacos , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Infecciones del Sistema Genital/inducido químicamente , Transportador 2 de Sodio-Glucosa/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Resultado del TratamientoRESUMEN
ABSTRACT Objective: This analysis compared the efficacy and safety of the sodium-glucose cotransporter-2 (SGLT2) inhibitor, dapagliflozin, and the dipeptidyl peptidase-4 (DPP4) inhibitor, saxagliptin, both added on to metformin. Materials and methods: This was a post-hoc analysis from a double-blind, randomized, 24-week clinical trial (NCT01606007) of patients with type 2 diabetes (T2D) inadequately controlled with metformin. We compared the dapagliflozin 10 mg (n = 179) and saxagliptin 5 mg (n = 176) treatment arms. Results: Dapagliflozin showed significantly greater mean reductions versus saxagliptin in HbA1c (difference versus saxagliptin [95% CI]: −0.32% [-0.54, −0.10]; p < 0.005), fasting plasma glucose (-0.98 [-1.42, −0.54] mmol/L; p < 0.0001), body weight (-2.39 [-3.08, −1.71] kg; p < 0.0001) and systolic blood pressure (SBP) (-3.89 [-6.15, −1.63] mmHg; p < 0.001). More dapagliflozintreated than saxagliptin-treated patients achieved the composite endpoint of HbA1c reduction ≥ 0.5%, weight loss ≥ 2 kg, SBP reduction ≥ 2 mmHg and no major/minor hypoglycemia (24% versus 7%). No major events of hypoglycemia were reported. More patients on dapagliflozin (6%) versus saxagliptin (0.6%) experienced genital infections. Conclusion: Dapagliflozin demonstrated greater glycemic efficacy than saxagliptin with additional benefits on weight and SBP, and the safety profile was consistent with previous studies.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Compuestos de Bencidrilo/uso terapéutico , Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Glucósidos/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Glucemia/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Adamantano/efectos adversos , Adamantano/uso terapéutico , Método Doble Ciego , Diabetes Mellitus Tipo 2/sangre , Dipéptidos/efectos adversos , Transportador 2 de Sodio-Glucosa/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéuticoRESUMEN
AIMS: To evaluate the glucose variability, oxidative stress, metabolic and cardiovascular responses after an aerobic exercise session in diabetic patients on treatment with metformin plus vildagliptin or glibenclamide. METHODS: Parallel clinical trial including patients with type 2 diabetes treated with metformin plus vildagliptin or glibenclamide for 12â¯weeks. Glucose variability, oxidative stress, metabolic (plasma glucose, insulin and glucagon-like-peptide-1) and cardiovascular responses were evaluated at rest, during and after a 30â¯min aerobic exercise session (70% of the peak heart rate). RESULTS: Thirteen patients were included, seven in vildagliptin group (METV) and six in glibenclamide group (METG), baseline glycated hemoglobin (HbA1c) 8.8⯱â¯0.3%. Treatment reduced HbA1c (1.2% and 1.5% for METV and METG, respectively). The aerobic exercise session did not change glucose variability in both groups. A decrease in glucose during exercise recovery was found, with area under the curve lower in the METG vs. METV (pâ¯=â¯0.04). After the intervention, systolic blood pressure (SBP) decreased in both groups. Patients treated with vildagliptin showed lower SBP variability compared to those treated with glibenclamide. CONCLUSIONS: Besides improvement in glucose control and reduction of SBP obtained by both treatments, lower blood pressure variability was observed in patients receiving vildagliptin. Glucose variability remained unaffected by both interventions and the exercise session.
Asunto(s)
Adamantano/análogos & derivados , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Ejercicio Físico/fisiología , Glucosa/metabolismo , Gliburida/uso terapéutico , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Adamantano/uso terapéutico , Anciano , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , VildagliptinaRESUMEN
OBJECTIVES: To determine whether the drug saxagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor which is utilized for the treatment of Diabetes Mellitus, has neuroprotective effects in the animal model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA) in rats. METHODS: Male Wistar rats (weighing 280-300 g) received a bilateral infusion of 6-OHDA in the substantia nigra. Twenty-four hours later, they were treated with saxagliptin (1 mg/kg, p.o) once daily, for 21 days. The motor function was evaluated using the open field and rotarod (RT) tests. In addition, cognition was assessed with the novel object recognition test (ORT). After the evaluation of the behavioural tests, the animals were transcardially perfused to perform immunohistochemistry staining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc). KEY FINDINGS: Saxagliptin impaired the memory of animals in the sham group. CONCLUSIONS: Saxagliptin treatment did not exhibit neuroprotection and it did not improve the cognitive and motor deficits in the 6-OHDA model of PD. Interestingly, when saxagliptin was administered to the sham animals, a cognitive decline was observed. Therefore, this drug should be investigated as a possible treatment for PTSD.
Asunto(s)
Adamantano/análogos & derivados , Conducta Animal/efectos de los fármacos , Dipéptidos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Adamantano/administración & dosificación , Adamantano/uso terapéutico , Animales , Dipéptidos/administración & dosificación , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Masculino , Memoria/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Oxidopamina , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/patología , Enfermedad de Parkinson Secundaria/fisiopatología , Ratas Wistar , Resultado del TratamientoRESUMEN
INTRODUCTION: Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems. Although guidelines clearly define first-line treatment, there are several other promising treatments. Vildagliptin is one of them, resulting in a mean lifetime increase of 0.31 years compared to metformin alone and 1.19 more life years compared to other metformin combinations. Considering observational data, life years with dual vildagliptin-containing treatments were 0.37 more compared to other dual treatments. However, its high cost versus generic metformin and its unclear safety profile weakens its subsequent cost-effectiveness. Consequently, the incorporation of vildagliptin or its combination with metformin is currently not recommended for the Brazilian Health Care System. This may change as more data becomes available.
Asunto(s)
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Adamantano/economía , Adamantano/farmacología , Adamantano/uso terapéutico , Brasil , Análisis Costo-Beneficio , Diabetes Mellitus Tipo 2/economía , Inhibidores de la Dipeptidil-Peptidasa IV/economía , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Quimioterapia Combinada , Humanos , Hipoglucemiantes/economía , Hipoglucemiantes/farmacología , Metformina/administración & dosificación , Metformina/economía , Metformina/uso terapéutico , Modelos Económicos , Nitrilos/economía , Nitrilos/farmacología , Pirrolidinas/economía , Pirrolidinas/farmacología , VildagliptinaRESUMEN
BACKGROUND: The multinational EDGE (Effectiveness of Diabetes control with vildaGliptin and vildagliptin/mEtformin) study assessed the effectiveness and tolerability of vildagliptin versus other oral antihyperglycemic drugs (OAD) when added to monotherapy in patients in the real-world setting. METHODS: Prospective, real-world observational study. The primary endpoint (PEP) was the proportion of patients achieving a reduction in HbA1c > 0.3% without peripheral edema, hypoglycemia, discontinuation, dueto gastrointestinal event, or weight gain > 5%. The secondary endpoint (SEP) was the proportion of patient achieving HbA1c < 7% (at month 12), without proven hypoglycemia or weight gain (≥ 3%). RESULTS: Of the 3,523 patients enrolled in Mexico, 2,847 were in the vildagliptin and 676 in the comparator cohort. The PEP was reached in 61.8 and 53.2% in the vildagliptin and comparator cohorts, respectively. The unadjusted odds ratio was 1.42 (95% CI: 1.19-1.68) in favor of vildagliptin. A similar advantage for vildagliptin-based therapies was seen for the SEP. The percentage was lower in the vildagliptin (n = 145; 5.0%) than in the comparator group (n = 95; 14.0%). CONCLUSION: Vildagliptin, added to a first-line OAD monotherapy, allows patients to reach target HbA1c without experiencing significant adverse events.
Asunto(s)
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Adamantano/efectos adversos , Adamantano/uso terapéutico , Administración Oral , Adulto , Anciano , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Masculino , México , Persona de Mediana Edad , Nitrilos/efectos adversos , Estudios Prospectivos , Pirrolidinas/efectos adversos , Resultado del Tratamiento , VildagliptinaRESUMEN
Hypertension and type 2 diabetes mellitus (DM) are among the main risk factors for the development of cardiovascular disease. Pharmacotherapy for DM should not only improve blood glucose control, but also provide beneficial glucose-independent cardiovascular effects. The central systolic blood pressure (SBP) has become more important than the brachial SBP in the assessment of cardiovascular risk.This case report describes the effect of vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, on the central SBP in a 54-year-old woman with hypertension and DM. She was submitted to applanation tonometry (AT) before and after vildagliptin association. AT of the radial artery is a non-invasive method that indirectly assesses arterial stiffness by calculating the central SBP and the augmentation index (AIx).After 3 months of follow-up using vildagliptin, central SBP and AIx were improved. Moreover, she presented better glycemic control.This case suggests an effect of DPP-4 inhibitor on arterial stiffness parameter (central SBP) in a hypertensive and diabetic patient, which shows a glucose-independent beneficial cardiovascular effect of this group of drugs.
Asunto(s)
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Adamantano/uso terapéutico , Glucemia/efectos de los fármacos , Presión Sanguínea , Femenino , Humanos , Persona de Mediana Edad , Rigidez Vascular/efectos de los fármacos , VildagliptinaRESUMEN
BACKGROUND: Cardiovascular disease, endothelial dysfunction, and oxidative stress are common complications among patients with type 2 diabetes (T2DM). In addition to the average blood glucose concentration, glycemic variability may be an important factor for the development of chronic diabetes complications. Patients with T2DM are treated with various types of oral glucose-lowering drugs. Exercise is considered to benefit the health of both healthy and unhealthy individuals, which has been confirmed by a number of scientific research studies in which the participants' health improved. Our general aim in this study will be to evaluate glucose variability after submaximal exercise test in patients receiving treatment with either vildagliptin or glibenclamide. The specific aims of this study are to evaluate the oxidative stress, endothelial function, and metabolic and cardiovascular responses to exercise under treatment with vildagliptin or glibenclamide. All these responses are important in patients with T2DM. METHODS/DESIGN: This study is a PROBE (Prospective, Randomized, Open-label, Blinded-Endpoint) design clinical trial. The estimated sample needed is 20 patients with T2DM. In addition to the routine treatment (metformin), patients will receive a second drug orally for 12 weeks: the METV group will receive metformin plus vildagliptin (50 mg twice daily), and the METG group will receive metformin plus glibenclamide (5 to 10 mg twice daily.). Before and after intervention, evaluation of glycemic variability, endothelial function, oxidative stress, and metabolic and cardiovascular response will be performed at rest, during and after a submaximal exercise test (30 minutes, with an intensity based at 10% under the heart rate at the second threshold). DISCUSSION: In addition to drug treatment, exercise is recommended for treatment of glycemic control in patients with T2DM, especially for its beneficial effects on blood glucose and HbA1c. Few studies have determined the effects of the association between exercise and oral glucose-lowering drugs. The study will be conducted to assess the metabolic and cardiovascular responses at rest, and during and after submaximal exercise in patients receiving one of two oral glucose-lowering drugs (vildagliptin or glibenclamide). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01867502 study release date: May-17-2013.
Asunto(s)
Adamantano/análogos & derivados , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Prueba de Esfuerzo , Gliburida/uso terapéutico , Hipoglucemiantes/uso terapéutico , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Proyectos de Investigación , Adamantano/efectos adversos , Adamantano/uso terapéutico , Biomarcadores/sangre , Glucemia/metabolismo , Brasil , Protocolos Clínicos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Gliburida/efectos adversos , Hemoglobina Glucada/metabolismo , Hemodinámica/efectos de los fármacos , Humanos , Hipoglucemiantes/efectos adversos , Nitrilos/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Pirrolidinas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , VildagliptinaRESUMEN
OBJECTIVE: To assess the proportion of patients on vildagliptin add-on dual therapy who respond to treatment over a 12 month follow-up, relative to comparator oral anti-diabetes dual therapy, in a usual care setting. RESEARCH DESIGN AND METHODS: Participants were patients with type 2 diabetes (T2DM) aged 18 years and older from 311 centers in Argentina, Colombia, Ecuador, Mexico and Venezuela. Patients were taking monotherapy with an oral anti-diabetes drug (OAD), and were prescribed a new add-on OAD based on the judgment of their personal physician. According to this choice, patients were assigned to one of the two cohorts: vildagliptin or comparator OADs. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients achieving an A1c drop >0.3% without edema, hypoglycemia, weight gain or discontinuation due to gastrointestinal (GI) events. The secondary endpoint was the proportion of patients with baseline A1c ≥7% who reached the goal of an A1c <7% without hypoglycemia or weight gain. RESULTS: The per-protocol population (a subset of the intention-to-treat population that excluded patients with pre-specified protocol deviations) comprised 3773 patients, 3002 in the vildagliptin cohort and 771 in the comparator cohort. The proportion of patients reaching the primary endpoint was higher in the vildagliptin cohort (60.3%) than the comparator cohort (50.7%), OR 1.48 (95% CI: 1.25-1.73). The same was observed for the secondary endpoint (44.8 versus 33.1%) OR 1.64 (95% CI: 1.37-1.98). The incidence of adverse events was low and similar between treatment cohorts. CONCLUSION: In a usual care setting, patients treated with a vildagliptin combination succeeded in lowering A1c to <7%, without weight gain, hypoglycemia or peripheral edema more often than patients treated with comparator combinations, without increased risk of adverse events. Key limitations are the observational nature of the study and its relatively limited 12 month timeframe.
Asunto(s)
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Adamantano/uso terapéutico , Administración Oral , Adulto , Anciano , Biomarcadores/sangre , Investigación sobre la Eficacia Comparativa , Diabetes Mellitus Tipo 2/sangre , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , América Latina , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , VildagliptinaRESUMEN
BACKGROUND: Currently, it is still unknown whether differences in glycemic control have any effect on glucose and insulin kinetics after vildagliptin administration. The aim of this study was to evaluate the effect of vildagliptin on glucose and insulin concentrations during a 24-h period in type 2 diabetes patients with different ranges of baseline hemoglobin A1c (A1C) levels. PATIENTS AND METHODS: A randomized, double-blind, crossover, placebo-controlled clinical trial was carried out in 12 drug-naive adult volunteers with type 2 diabetes and overweight or obesity. Subjects had fasting glucose values between 7.2 and 13.3 mmol/L. Six patients had A1C between 7.0% and 8.4% (Group A), and the remaining subjects had A1C between 8.5% and 10.0% (Group B). Patients received oral administration of vildagliptin (50 mg twice daily) or placebo in a crossover manner for two consecutive days. Until the second day of the interventions, glucose and insulin concentrations were measured every hour during a 24-h period, and areas under the curve (AUCs) were calculated. Statistical analyses were evaluated with Wilcoxon and Mann-Whitney U tests. RESULTS: There were significant decreases in glucose concentrations after vildagliptin administration in both groups when comparing placebo in all measurements throughout the 24-h period and in the AUC. There were no significant changes in insulin concentration in both groups after vildagliptin administration when comparing placebo in all measurements throughout the 24-h period and in the AUC. CONCLUSIONS: Vildagliptin administration improved glucose control during a 24-h period in type 2 diabetes patients, independent of the basal A1C level, without changes in insulin levels.
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Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Péptido 1 Similar al Glucagón/agonistas , Hemoglobina Glucada/análisis , Hiperglucemia/prevención & control , Insulina/sangre , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Adamantano/efectos adversos , Adamantano/uso terapéutico , Adulto , Glucemia/análisis , Índice de Masa Corporal , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Método Doble Ciego , Femenino , Humanos , Insulina/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Cinética , Masculino , Persona de Mediana Edad , Nitrilos/efectos adversos , Obesidad/complicaciones , Sobrepeso/complicaciones , Pirrolidinas/efectos adversos , VildagliptinaRESUMEN
BACKGROUND AND AIMS: It is believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus. Several strategies have been developed with the objective of minimizing diabetic complications. Among these, inhibitors of dipeptidyl peptidase-IV (DPP-IV), which act by blocking degradation of incretin hormones, glucagon-like peptide hormone (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), have been the focus of many studies. It is known that, among the effects of incretins, we highlight its insulinotropic and cytoprotective effects on pancreatic ß-cells. The objective of this study was to evaluate the possible protective effects of treatment with vildagliptin, a DPP-IV inhibitor, in ß-cells in an experimental model of type 1 diabetes induced by streptozotocin (STZ). METHODS: Rats were treated for 4 weeks with vildagliptin at concentrations of 5 and 10 mg/kg. In order to observe the pancreatic damage and the possible protective effects of vildagliptin treatment, we measured stress markers TBARS and protein carbonyl, antioxidant enzymes SOD and catalase, and analyzed pancreatic histology. RESULTS: The treatment was effective in modulating stress in pancreatic tissue, both by reducing levels of stress markers as well as by increasing activity of SOD and catalase. After analyzing the pancreatic histology, we found that vildagliptin was also able to preserve islets and pancreatic ß-cells, especially at the concentration of 5 mg/kg. CONCLUSION: Thus, our results suggest that vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats. However, to evaluate the real potential of this medication in type 1 diabetes, further studies are needed.
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Adamantano/análogos & derivados , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/patología , Nitrilos/farmacología , Estrés Oxidativo/efectos de los fármacos , Pirrolidinas/farmacología , Adamantano/farmacología , Adamantano/uso terapéutico , Animales , Antioxidantes/metabolismo , Biomarcadores , Glucemia/análisis , Peso Corporal , Catalasa/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Dipeptidil Peptidasa 4/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Femenino , Incretinas/sangre , Insulina/sangre , Células Secretoras de Insulina/metabolismo , Nitrilos/uso terapéutico , Oxidación-Reducción , Pirrolidinas/uso terapéutico , Ratas , Estreptozocina , Superóxido Dismutasa/metabolismo , VildagliptinaRESUMEN
OBJECTIVE: To assess the effect of two hypoglycemic drugs on ischemic preconditioning (IPC) patients with type 2 diabetes and coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: We performed a prospective study of 96 consecutive patients allocated into two groups: 42 to group repaglinide (R) and 54 to group vildagliptin (V). All patients underwent two consecutive exercise tests (ET1 and ET2) in phase 1 without drugs. In phase 2, 1 day after ET1 and -2, 2 mg repaglinide three times daily or 50 mg vildagliptin twice daily was given orally to patients in the respective group for 6 days. On the seventh day, 60 min after 6 mg repaglinide or 100 mg vildagliptin, all patients underwent two consecutive exercise tests (ET3 and ET4). RESULTS: In phase 1, IPC was demonstrated by improvement in the time to 1.0 mm ST-segment depression and rate pressure product (RPP). All patients developed ischemia in ET3; however, 83.3% of patients in group R experienced ischemia earlier in ET4, without significant improvement in RPP, indicating the cessation of IPC (P < 0.0001). In group V, only 28% of patients demonstrated IPC cessation, with 72% still having the protective effect (P < 0.0069). CONCLUSIONS: Repaglinide eliminated myocardial IPC, probably by its effect on the KATP channel. Vildagliptin did not damage this protective mechanism in a relevant way in patients with type 2 diabetes and CAD, suggesting a good alternative treatment in this population.
Asunto(s)
Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Precondicionamiento Isquémico , Adamantano/efectos adversos , Adamantano/análogos & derivados , Adamantano/uso terapéutico , Anciano , Carbamatos/efectos adversos , Carbamatos/uso terapéutico , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Nitrilos/efectos adversos , Nitrilos/uso terapéutico , Piperidinas/efectos adversos , Piperidinas/uso terapéutico , Estudios Prospectivos , Pirrolidinas/efectos adversos , Pirrolidinas/uso terapéutico , VildagliptinaRESUMEN
OBJECTIVE: To evaluate the effectiveness of adding vildagliptin to the treatment of patients with inadequately controlled type 2 diabetes mellitus (T2DM) treated with a combination of metformin and a sulphonylurea. SUBJECTS AND METHODS: 37 T2DM patients with HbA1c ranging from 7.7% to 12.4% (mean of 9.30 ± 1.38), despite the use of metformin in combination with a sulphonylurea, were additionally treated with vildagliptin (100 mg/day) for at least 6 months. RESULTS: During triple oral therapy (TOT) HbA1c levels < 7% were achieved in 11 patients (29.7%), whereas levels of fasting plasma glucose (FPG) < 120 mg/dL were observed in 12 patients (32.4%). Both findings were observed in 10 patients (27.0%). Compared to nonresponsive subjects, lower mean baseline HbA1c and FPG levels were seen in responsive patients, but the difference was only statistically significant for fasting plasma glucose (FPG). Moreover, there was considerable overlap between the two groups. CONCLUSION: Our preliminary results suggest that TOT with metformin, a sulphonylurea and vildagliptin may be useful for some T2DM patients nonresponsive to combination therapy with metformin and sulphonylurea.
Asunto(s)
Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Adamantano/uso terapéutico , Administración Oral , Adulto , Análisis de Varianza , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Quimioterapia Combinada/métodos , Ayuno/sangre , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del Tratamiento , VildagliptinaRESUMEN
OBJECTIVE: To evaluate the effectiveness of adding vildagliptin to the treatment of patients with inadequately controlled type 2 diabetes mellitus (T2DM) treated with a combination of metformin and a sulphonylurea. SUBJECTS AND METHODS: 37 T2DM patients with HbA1c ranging from 7.7 percent to 12.4 percent (mean of 9.30 ± 1.38), despite the use of metformin in combination with a sulphonylurea, were additionally treated with vildagliptin (100 mg/day) for at least 6 months. RESULTS: During triple oral therapy (TOT) HbA1c levels < 7 percent were achieved in 11 patients (29.7 percent), whereas levels of fasting plasma glucose (FPG) < 120 mg/dL were observed in 12 patients (32.4 percent). Both findings were observed in 10 patients (27.0 percent). Compared to nonresponsive subjects, lower mean baseline HbA1c and FPG levels were seen in responsive patients, but the difference was only statistically significant for fasting plasma glucose (FPG). Moreover, there was considerable overlap between the two groups. CONLUSION: Our preliminary results suggest that TOT with metformin, a sulphonylurea and vildagliptin may be useful for some T2DM patients nonresponsive to combination therapy with metformin and sulphonylurea.
OBJETIVO: Avaliar a eficácia da adição de vildagliptina ao tratamento de pacientes com diabetes melito tipo 2 (DM2) inadequadamente controlados com a terapia de combinação com metformina e sulfonilureia. SUJEITOS E MÉTODOS: 37 pacientes com DM2 e HbA1c variando entre 7,7 por cento e 12,4 por cento (média, 9,30 ± 1,38), apesar do uso de metformina associada a uma sulfonilureia, foram adicionalmente tratados com vildagliptina (100 mg/dia) durante, pelo menos, 6 meses. RESULTADOS: Durante a terapia oral tripla TOT), níveis de HbA1c < 7 por cento foram alcançados em 11 pacientes (27,9 por cento), enquanto a glicemia de jejum (GJ) < 120 mg/dL foi observada em 12 pacientes (32,4.1 por cento). Ambos os resultados foram descritos em 10 pacientes (27,0 por cento). Em comparação com indivíduos não responsivos, os pacientes responsivos tinham níveis basais mais baixos de HbA1c e GJ, mas a diferença foi estatisticamente significativa somente para glicemia de jejum. Além disso, houve grande sobre-posição entre os dois grupos. CONSLUSÃO: Nossos resultados preliminares sugerem que a TOT com metformina, uma sulfonilureia e vildagliptina pode ser útil para alguns pacientes com DM2 não responsivos à combinação com metformina e uma sulfonilureia.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adamantano/análogos & derivados , /tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Nitrilos/uso terapéutico , Pirrolidinas/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Administración Oral , Análisis de Varianza , Adamantano/uso terapéutico , Glucemia/metabolismo , /sangre , Quimioterapia Combinada/métodos , Ayuno/sangre , Hemoglobina Glucada/metabolismo , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
This review summarizes the importance and recent discoveries of the use of adamantane derivatives in Medicinal Chemistry. We have organized the article in 4 sections: 1) Absorption, Distribution, Metabolism, or Excretion (ADME) properties 2) Hydrophobic Effects 3) Ion Channels and 4) Rigid scaffold. Within each section, we have provided examples of how the adamantane group changes the properties of known drugs or provides a important pharmacophore for the design of new drugs.
Asunto(s)
Adamantano/uso terapéutico , Antivirales/uso terapéutico , Química Farmacéutica , Adamantano/análogos & derivados , Adamantano/farmacología , Antivirales/farmacología , Humanos , Modelos Biológicos , Orthomyxoviridae/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
AIMS: Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy. METHODS AND PATIENTS: A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to Asunto(s)
Adamantano/análogos & derivados
, Glucemia/efectos de los fármacos
, Diabetes Mellitus Tipo 2/tratamiento farmacológico
, Dipéptidos/uso terapéutico
, Hipoglucemiantes/uso terapéutico
, Compuestos de Sulfonilurea/uso terapéutico
, Adamantano/uso terapéutico
, Adolescente
, Adulto
, Anciano
, Análisis de Varianza
, Método Doble Ciego
, Quimioterapia Combinada
, Humanos
, Persona de Mediana Edad
, Resultado del Tratamiento
, Adulto Joven
RESUMEN
AIM: The study aim was to evaluate the efficacy and safety of initial combination therapy with saxagliptin + metformin vs. saxagliptin or metformin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycaemic control. METHODS: In this multicentre, randomized, double-blind, active-controlled phase 3 trial, 1306 treatment-naïve patients with T2D >or=18 to Asunto(s)
Adamantano/análogos & derivados
, Diabetes Mellitus Tipo 2/tratamiento farmacológico
, Dipéptidos/uso terapéutico
, Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico
, Hipoglucemiantes/uso terapéutico
, Metformina/uso terapéutico
, Adamantano/administración & dosificación
, Adamantano/uso terapéutico
, Adulto
, Glucemia
, Dipéptidos/administración & dosificación
, Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación
, Método Doble Ciego
, Quimioterapia Combinada/métodos
, Ayuno
, Femenino
, Hemoglobina Glucada/metabolismo
, Humanos
, Hipoglucemiantes/administración & dosificación
, Masculino
, Metformina/administración & dosificación
, Persona de Mediana Edad
, Periodo Posprandial
, Resultado del Tratamiento
RESUMEN
BACKGROUND: Recent influenza antiviral resistance studies reveal an alarming increase in both adamantanes and neuraminidase inhibitors (NAIs) resistant viral strains worldwide, particularly in Asia, Europe and the United States. OBJECTIVES: In this study, we have evaluated influenza virus resistance in Central and South America. METHODS: Influenza viruses, isolated from symptomatic patients throughout Central and South America in 2005-2008 were analyzed for inhibitor resistance. The M2 and NA genes of influenza viruses were sequenced and resistance was inferred by comparison with published sequences and known resistant mutations. RESULTS: Our results indicate that: (i) resistance to adamantanes was seen in the majority (95.5%) of the influenza A/H3N2 isolates but only in one isolate of the influenza A/H1N1 viruses; (ii) resistance to NAIs began to be detected in A/H1N1 isolates from Central America in 2008; and (iii) none of the influenza B viruses analyzed were resistant to NAIs. CONCLUSIONS: These findings suggest a limited effectiveness of influenza inhibitors due to the detection of resistance among A/H1 and A/H3 viruses.