RESUMO
BACKGROUND/AIM: Vildagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors that have been shown to improve hyperglycemia in clinical trials among patients with type 2 diabetes. However, few studies have examined the efficacy of vildagliptin in patients with diabetic kidney disease (DKD). PATIENTS AND METHODS: Eight patients with DKD received oral vildagliptin 50-100 mg/day. The duration of diabetes was 6.7±5.9 years and observation period was 23.6±9.8 months. Changes in fasting blood glucose, and hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and urine protein-to-creatinine ratio (UPCR) were studied before and after the administration of vildagliptin. RESULTS: Vildagliptin treatment significantly decreased fasting blood glucose and HbA1c, compared to baseline (132±56 mg/dl, p=0.036, 6.0±0.3, p=0.041, respectively). UPCR tended to be decreased, albeit without statistical significance. However, eGFR was decreased after the administration of vildagliptin. No significant adverse effects were observed in all patients during the study. CONCLUSION: Although the sample size was limited and the observation period was brief, vildagliptin was found to be an effective and reasonably well-tolerated treatment for patients with DKD.
Assuntos
Adamantano , Glicemia , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores da Dipeptidil Peptidase IV , Taxa de Filtração Glomerular , Hemoglobinas Glicadas , Nitrilas , Pirrolidinas , Vildagliptina , Humanos , Vildagliptina/uso terapêutico , Vildagliptina/efeitos adversos , Vildagliptina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Nefropatias Diabéticas/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Taxa de Filtração Glomerular/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/análise , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Adamantano/efeitos adversos , Resultado do Tratamento , Pirrolidinas/uso terapêutico , Pirrolidinas/efeitos adversos , Pirrolidinas/administração & dosagem , Nitrilas/uso terapêutico , Nitrilas/efeitos adversos , Nitrilas/administração & dosagem , Creatinina/sangueRESUMO
AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.
Assuntos
Adamantano , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Dipeptídeos , Quimioterapia Combinada , Glucosídeos , Hemoglobinas Glicadas , Hipoglicemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Metformina/uso terapêutico , Metformina/administração & dosagem , Metformina/efeitos adversos , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Masculino , Feminino , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Pessoa de Meia-Idade , Dipeptídeos/efeitos adversos , Dipeptídeos/administração & dosagem , Dipeptídeos/uso terapêutico , Adamantano/análogos & derivados , Adamantano/administração & dosagem , Adamantano/efeitos adversos , Adamantano/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Idoso , Resultado do Tratamento , Hipoglicemia/induzido quimicamente , Compostos de Sulfonilureia/uso terapêutico , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Adulto , Aumento de Peso/efeitos dos fármacos , Fosfato de Sitagliptina/uso terapêutico , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/efeitos adversosAssuntos
Adamantano , Adamantano/análogos & derivados , Dermatite Alérgica de Contato , Dermatite Ocupacional , Dipeptídeos , Olanzapina , Humanos , Adamantano/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/diagnóstico , Olanzapina/efeitos adversos , Dermatite Ocupacional/etiologia , Dipeptídeos/efeitos adversos , Testes do Emplastro , Masculino , Antipsicóticos/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Pessoa de Meia-Idade , Adulto , FemininoRESUMO
OBJECTIVES: This post hoc analysis of the RAJ2 study assessed long-term safety and effectiveness of peficitinib 100 mg/day for treatment of rheumatoid arthritis. METHODS: Eligible patients previously completed two Phase 3 (RAJ3 and RAJ4) studies of peficitinib in Asia. All patients received peficitinib 100 mg/day at RAJ2 Week (W)0; dose change to 50 mg/day or 150 mg/day was permitted. Safety endpoints included treatment-emergent adverse events and laboratory test results. Effectiveness endpoints included peficitinib exposure pattern, achievement of Clinical Disease Activity Index (CDAI) remission by peficitinib exposure pattern at W0 and W48, and association of demographics/characteristics with CDAI remission at W0 and W48. RESULTS: Overall, no new safety findings were reported at W48, and renal function was unaffected. Of patients included in effectiveness analyses at W48, 70.9% (451/636) had maintained peficitinib 100 mg/day since W0. Of patients who achieved CDAI remission at W0 and maintained peficitinib 100 mg/day to W48, 50.3% (79/157) maintained CDAI remission to W48. Low disease activity and a lower number of prior disease-modifying antirheumatic drugs were significantly associated with CDAI remission at W48. CONCLUSIONS: Long-term peficitinib treatment at a dose of 100 mg/day was generally well tolerated and, following induction therapy, maintained effectiveness through to W48.
Assuntos
Antirreumáticos , Artrite Reumatoide , Niacinamida , Indução de Remissão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Resultado do Tratamento , Adulto , República da Coreia , Taiwan , Idoso , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Niacinamida/efeitos adversos , Niacinamida/administração & dosagem , Japão , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Adamantano/efeitos adversos , Adamantano/administração & dosagemRESUMO
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.