RESUMEN
Henagliflozin proline and metformin hydrochloride sustained-release tablets (HR20033) are a fixed-dose combination of the novel, highly selective, and effective sodium-glucose cotransporter-2 inhibitor henagliflozin, with a metformin sustained-release layer for the treatment of type 2 diabetes mellitus in conjunction with dietary control and exercise. The aims of this study were to investigate the effect of a high-fat diet on the pharmacokinetics of henagliflozin and metformin after a single administration of HR20033 and the effect of repeated oral administration of HR20033 on their pharmacokinetics in healthy volunteers. The food-effect clinical study involved 18 healthy subjects randomized to receive either HR20033 in the fasted condition followed by HR20033 in the fed condition or the reverse schedule, with the two doses separated by a washout period of at least 7 days. The multiple-dose clinical study was conducted on 10 healthy subjects. In the food-effect study, compared with those in the fasted condition, the area under the blood concentration curve (AUC) and peak concentration (Cmax ) of henagliflozin decreased by 12.64% and 40.89%, respectively, while the AUC of metformin increased by 31.13% and Cmax decreased by 7.09% in the fed state. There was no significant accumulation of HR20033 in the body after multiple oral doses. No serious adverse event was observed in either of the two clinical studies. Food did not have a clinically meaningful effect on the absorption of HR20033.
Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Metformina/farmacocinética , Hipoglucemiantes/farmacocinética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Voluntarios Sanos , Preparaciones de Acción Retardada , Pueblos del Este de Asia , Área Bajo la CurvaRESUMEN
Objective: To analyze the efficacy and safety of three novel hypoglycemic agents, glucagon-like peptidyl-1 receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter two inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM) patients with severe chronic kidney disease (CKD) (defined in this study as CKD stage 3 B or above, eGFR< 45 mL/min/1.73 m²) based on important RCTs to date. Methods: We retrieved studies published before April 15, 2022, from EMBASE, PubMed/MEDLINE, Cochrane Library and included randomized controlled trials in which the participants were patients with T2DM and severe CKD. Frequentist methods were used in the network meta-analysis. Results: Nineteen studies of 17 trials involving 6,607 participants met our inclusion criteria. Compared with placebo and DPP-4i, SGLT2i demonstrated a significantly lower incidence of serious renal-related adverse events or renal death, and the odds ratios (OR) were 0.69 (0.58, 0.81) and 0.63 (0.40, 1.00), respectively. Compared with placebo, SGLT2i significantly reduced the incidence of all-cause death and severe AE; the ORs were 0.72 (0.55, 0.94) and 0.65 (0.47, 0.91), respectively. Compared with placebo, DPP-4i significantly reduced the level of HbA1c, and the difference between mean changes from baseline was -0.36 (-0.63, -0.09). Conclusions: Patients with T2DM complicated by severe CKD may benefit from SGLT2i. SGLT2i can reduce the incidence of serious renal-related AEs or renal death, as well as severe side effects, and has a positive effect on the patient's renal function and survival, even for only CKD patients can also be considered. GLP-1 RAs can be used as a supplement if blood sugar control is poor. For dialysis patients, DPP-4i can assist blood glucose control, reduce insulin dosage, and reduce the risk of hypoglycemia. Systematic review registration: INPLASY https://inplasy.com/inplasy-2021-12-0106/, identifier INPLASY2021120106.
Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Inhibidores de la Dipeptidil-Peptidasa IV , Insuficiencia Renal Crónica , Humanos , Hipoglucemiantes/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metaanálisis en Red , Hemoglobina Glucada/análisis , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
OBJECTIVES: To compare the efficacy of transarterial embolization (TAE) with polyvinyl alcohol (PVA) particles alone and lipiodol-bleomycin emulsion (LBE) plus PVA particles for patients with unresectable large symptomatic focal nodular hyperplasia (FNH). METHODS: We performed a retrospective analysis of patients who underwent TAE either with PVA particles alone (group A, n = 46) or LBE plus PVA particles (group B, n = 35) for large (≥ 7 cm) symptomatic FNH between January 2002 and February 2019. Propensity score matching (PSM) (1:1) was performed to adjust for potential baseline confounders. Technical success, adverse events (AEs), symptom relief, and changes in the lesion size after TAE were evaluated. Statistical analysis included Wilcoxon rank sum test and χ2 test. RESULTS: After PSM, no significant differences in baseline characteristics were found between the groups (31 in group A and 31 in group B, with a mean age of 31 years). Technical success was achieved in all patients (100%), without major AEs in both groups. Complete resolution of the abdominal symptoms was reported in 77.4% in group A and 100% in group B (p = 0.037) during a mean follow-up period of 72 months; complete resolution (CR) of the FNH rate was significantly higher in group B than in group A (93.6% vs. 67.7%; p = 0.019). CONCLUSION: Compared with the use PVA particles alone, TAE with LBE plus PVA particles in the treatment of patients with large symptomatic FNH had a significantly higher rates of CR of the FNH and complete relief of the symptoms. KEY POINTS: ⢠Transarterial embolization (TAE) with lipiodol-bleomycin emulsion (LBE) plus PVA particles for the large symptomatic FNH yielded better results than with PVA particles alone, in terms of complete resolution of FNH lesions (93.6% vs 67.7%) and complete relief of the abdominal symptoms (100% vs 77.4%) during a mean follow-up period of 72 months (38-170 months). ⢠No major complications were recorded in both groups, and no significant difference in the incidence of postembolization syndrome were observed between the two groups.
Asunto(s)
Embolización Terapéutica , Hiperplasia Nodular Focal , Neoplasias Hepáticas , Adulto , Bleomicina , Embolización Terapéutica/métodos , Emulsiones , Aceite Etiodizado , Hiperplasia Nodular Focal/patología , Humanos , Neoplasias Hepáticas/terapia , Alcohol Polivinílico , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Hypertension is a long-term medical condition. Mobile health (mHealth) services can help out-of-hospital patients to self-manage. However, not all management is effective, possibly because the behavior mechanism and behavior preferences of patients with various characteristics in hypertension management were unclear. OBJECTIVE: The purpose of this study was to (1) explore patient multibehavior engagement trails in the pathway-based hypertension self-management, (2) discover patient behavior preference patterns, and (3) identify the characteristics of patients with different behavior preferences. METHODS: This study included 863 hypertensive patients who generated 295,855 use records in the mHealth app from December 28, 2016, to July 2, 2020. Markov chain was used to infer the patient multibehavior engagement trails, which contained the type, quantity, time spent, sequence, and transition probability value (TP value) of patient behavior. K-means algorithm was used to group patients by the normalized behavior preference features: the number of behavioral states that a patient performed in each trail. The pages in the app represented the behavior states. Chi-square tests, Z-test, analyses of variance, and Bonferroni multiple comparisons were conducted to characterize the patient behavior preference patterns. RESULTS: Markov chain analysis revealed 3 types of behavior transition (1-way transition, cycle transition, and self-transition) and 4 trails of patient multibehavior engagement. In perform task trail (PT-T), patients preferred to start self-management from the states of task blood pressure (BP), task drug, and task weight (TP value 0.29, 0.18, and 0.20, respectively), and spent more time on the task food state (35.87 s). Some patients entered the states of task BP and task drug (TP value 0.20, 0.25) from the reminder item state. In the result-oriented trail (RO-T), patients spent more energy on the ranking state (19.66 s) compared to the health report state (13.25 s). In the knowledge learning trail (KL-T), there was a high probability of cycle transition (TP value 0.47, 0.31) between the states of knowledge list and knowledge content. In the support acquisition trail (SA-T), there was a high probability of self-transition in the questionnaire (TP value 0.29) state. Cluster analysis discovered 3 patient behavior preference patterns: PT-T cluster, PT-T and KL-T cluster, and PT-T and SA-T cluster. There were statistically significant associations between the behavior preference pattern and gender, education level, and BP. CONCLUSIONS: This study identified the dynamic, longitudinal, and multidimensional characteristics of patient behavior. Patients preferred to focus on BP, medications, and weight conditions and paid attention to BP and medications using reminders. The diet management and questionnaires were complicated and difficult to implement and record. Competitive methods such as ranking were more likely to attract patients to pay attention to their own self-management states. Female patients with lower education level and poorly controlled BP were more likely to be highly involved in hypertension health education.