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AIM: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) continuation, in people with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-label, prospective, randomized, parallel-group comparison study, participants receiving DPP-4is were either switched to oral semaglutide (3-14 mg/day) or continued on DPP-4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored. RESULTS: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP-4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP-4i continuation [-0.65 (95% confidence interval: -0.79, -0.51) vs. +0.05 (95% confidence interval: -0.07, 0.16) (p < .001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP-4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2-R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms. CONCLUSIONS: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP-4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Hemoglobina Glucada , Control Glucémico , Estudios Prospectivos , Hipoglucemiantes/efectos adversos , Péptidos Similares al Glucagón/efectos adversos , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/uso terapéuticoRESUMEN
AIM: To investigate the effects of switching from liraglutide or dulaglutide to once-weekly semaglutide on glycaemic control and treatment satisfaction in patients with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-labelled, prospective, randomized, parallel-group comparison study, patients treated with liraglutide 0.9-1.8 mg/day (plan A) or dulaglutide 0.75 mg/week (plan B) were either switched to semaglutide or continued current therapy. The primary endpoint was the mean change in glycated haemoglobin over 24 weeks. The secondary endpoints included the changes of Diabetes Treatment Satisfaction Questionnaire scores, body weight and metabolic indices. RESULTS: In total, 110 patients were enrolled, and 10 were excluded; therefore, 37 patients in plan A and 63 patients in plan B completed the study. Glycated haemoglobin levels were significantly reduced in the semaglutide group in both plans [plan A, 7.8% ± 1.0% to 7.8% ± 0.7% (liraglutide) vs. 7.9% ± 0.7% to 7.3% ± 0.7% (semaglutide), p < .01; plan B, 7.8% ± 1.0% to 7.9% ± 1.2% (dulaglutide) vs. 7.8% ± 0.8% to 7.1% ± 0.6% (semaglutide), p < .01]. Semaglutide also improved Diabetes Treatment Satisfaction Questionnaire scores in both groups (plan A, +0.1 vs. +8.3, p < .01; plan B, -1.2 vs. +3.5, p < .01). Switching from dulaglutide yielded greater reductions in body weight and improved metabolic parameters. CONCLUSIONS: Once-weekly semaglutide administration improved glycaemic control and treatment satisfaction after switching from liraglutide or dulaglutide. These results highlighted a useful treatment option for patients with metabolic abnormalities despite glucagon-like receptor-1 receptor agonist treatment.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Liraglutida/efectos adversos , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada , Estudios Prospectivos , Control Glucémico , Satisfacción del Paciente , Péptidos Similares al Glucagón/efectos adversos , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Proteínas Recombinantes de Fusión/efectos adversos , Peso Corporal , Satisfacción PersonalRESUMEN
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are well-established means of improving glycemia and preventing cardio-renal events in patients with type 2 diabetes. However, their efficacy and safety have yet to be fully characterized in patients with type 1 diabetes (T1D). We studied patients with T1D who regularly attended one of five diabetes centers and treated with an SGLT2i (ipragliflozin or dapagliflozin) for >52 weeks, and the changes in HbA1c, body mass, insulin dose, and laboratory data were retrospectively evaluated and adverse events (AEs) recorded during December 2018 to April 2021. A total of 216 patients with T1D were enrolled during the period. Of these, 42 were excluded owing to short treatment periods and 15 discontinued their SGLT2i. The mean changes in glycated hemoglobin (HbA1c), body mass, and insulin dose were -0.4%, -2.1 kg, and -9.0%, respectively. The change in HbA1c was closely associated with the baseline HbA1c (p < 0.001), but not with the baseline body mass or renal function. The basal and bolus insulin doses decreased by 18.2% and 12.6%, respectively, in participants with a baseline HbA1c <8%. The most frequent AE was genital infection (2.8%), followed by diabetic ketoacidosis (DKA; 1.4%). None of the participants experienced severe hypoglycemic events. In conclusion, the administration of an SGLT2i in addition to intensive insulin treatment in patients with T1D improves glycemic control and body mass, without increasing the incidence of hypoglycemia or DKA.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Glucemia , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Cetoacidosis Diabética/inducido químicamente , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/prevención & control , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/efectos adversos , Insulina/uso terapéutico , Estudios Retrospectivos , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversosRESUMEN
This multicentre, prospective, randomized, open-label, blinded-endpoint, parallel-group, short-term (4-5 weeks) controlled trial was conducted to investigate the superiority of the effect of reducing mean amplitude of glycaemic excursions (MAGE) during meal tolerance tests (MTTs) for the combination of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter-2 (SGLT2) inhibitor compared with SGLT2 inhibitor monotherapy. Ninety-nine patients with type 2 diabetes who were taking teneligliptin (20 mg/d) were randomized to one of the following two groups: those who switched to 100 mg/d of canagliflozin (SWITCH group) or those who added 100 mg/d of canagliflozin (COMB group). MAGE in the COMB group was significantly decreased compared with that in the SWITCH group (COMB 117.5 ± 39.8 to 92.2 ± 28.0 mg/dL vs SWITCH 110.7 ± 29.8 to 104.2 ± 27.6 mg/dL; P<0.01). Mean blood glucose decreased significantly during MTTs in both groups, although the extent of the reduction was significantly greater in the COMB group (COMB 142.3 ± 28.7 to 119.5 ± 25.1 mg/dL vs SWITCH 146.4 ± 25.5 to 135.5 ± 22.4 mg/dL; P < 0.01). SGLT2 inhibitor combined with DPP-4 inhibitor therapy strongly reduced glycaemic fluctuation compared with SGLT2 inhibitor monotherapy.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Simportadores , Glucemia , Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/uso terapéutico , Quimioterapia Combinada , Humanos , Hipoglucemiantes/uso terapéutico , Estudios Prospectivos , Pirazoles , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , TiazolidinasRESUMEN
The effects of dapagliflozin (DAP) and pioglitazone (PIO) on body weight and glycaemic control were compared in patients with type 2 diabetes mellitus. Seventy-one patients on PIO were either switched to DAP (n = 36) at 5 mg per day or continued on PIO (n = 35). Primary endpoints were superiority of body weight loss and non-inferiority of HbA1c level after 24 weeks with DAP. Body weight decrease was greater with DAP than with PIO (75.3 ± 14.9 to 71.3 ± 15.1 kg vs. 74.7 ± 13.8 to 75.2 ± 13.9 kg; P < 0.01). Change in the HbA1c level was comparable (P = 0.64). The level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and urinary albumin : creatinine ratio (ACR) decreased only with DAP (NT-proBNP, P < 0.01; ACR, P = 0.02), and the change in NT-proBNP correlated negatively with baseline NT-proBNP level (ρ = -0.68, P < 0.01) and log-converted ACR (ρ = -0.35, P < 0.05). DAP promotes body weight loss in type 2 diabetes mellitus and may decrease fluid retention, thus reducing the occurrence of cardiovascular events.
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Compuestos de Bencidrilo/uso terapéutico , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Sustitución de Medicamentos , Metabolismo Energético/efectos de los fármacos , Glucósidos/uso terapéutico , Pioglitazona/uso terapéutico , Anciano , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
We compared treatment satisfaction between daily dipeptidyl peptidase-4 (DPP-4) inhibitors and a weekly DPP-4 inhibitor in patients with type 2 diabetes. The study was a 12-week, open-label, randomized, multicenter, controlled trial. Participants were Japanese patients with type 2 diabetes who had received daily DPP-4 inhibitors for more than 3 months. Patients were randomly assigned to a treatment cohort: (1) a group that continued taking daily DPP-4 inhibitors (daily group); or (2) a group that switched from daily DPP-4 inhibitors to a weekly DPP-4 inhibitor, trelagliptin (weekly group). The primary outcome was the change in treatment satisfaction levels from baseline to 12 weeks between the two groups, according to Diabetes Treatment Satisfaction Questionnaire (DTSQ) and Diabetes Therapy-Related Quality of Life (DTR-QOL) questionnaire scores. The changes in glycemic control and body weight were also assessed. Of 49 patients initially enrolled in the study, 47 completed the study. The change in DTSQ scores in the weekly group was not significantly different from that in the daily group. However, the improvements in total score and subscale domains 1 and 2 in the DTR-QOL analysis, which relate to burden on social/daily activities and anxiety/dissatisfaction with treatment, were significantly greater in the weekly group than the daily group (p = 0.048, 0.013 and 0.045, respectively). Mean changes in glycated hemoglobin levels and body weight were comparable between the groups. Switching from daily DPP-4 inhibitors to a weekly DPP-4 inhibitor, trelagliptin, could partially improve treatment satisfaction levels in patients with type 2 diabetes without affecting glycemic control.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Sustitución de Medicamentos , Hipoglucemiantes/administración & dosificación , Satisfacción del Paciente , Uracilo/análogos & derivados , Adulto , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Esquema de Medicación , Sustitución de Medicamentos/psicología , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/efectos adversosRESUMEN
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin. METHODS: In this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500-750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed. RESULTS: Ninety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m2; HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (- 0.80 ± 0.38% vs. - 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (- 0.51 [- 1.08-0.06]% vs. - 0.58 [- 1.20-0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66-0.62; p < 0.01), the change did not differ significantly between the two groups (- 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 µg/mL vs. 0.01 µg/mL; p < 0.01). CONCLUSIONS: Regardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis.
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Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Endotelio Vascular/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Nitrilos/administración & dosificación , Pirrolidinas/administración & dosificación , Adamantano/administración & dosificación , Adulto , Anciano , Diabetes Mellitus Tipo 2/metabolismo , Quimioterapia Combinada , Endotelio Vascular/fisiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , VildagliptinaRESUMEN
CONTEXT: Whether continuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) or switching to oral semaglutide is more beneficial for ß-cell function is unclear. OBJECTIVE: To assess the efficacy of switching from DPP-4is to oral semaglutide for ß-cell function compared with DPP-4i continuation. METHODS: Post hoc analysis of SWITCH-SEMA 2, a multicenter prospective randomized controlled trial on the switch to oral semaglutide vs DPP-4i continuation without dose adjustment for 24 weeks in subjects with type 2 diabetes treated with DPP-4is, was conducted. Changes in markers for glucose metabolism, including homeostatic model assessment (HOMA2) scores and disposition index (DI), were compared between the groups. RESULTS: A total of 146 subjects (semaglutide group, 69; DPP-4i group, 77) were analyzed. In the semaglutide group, glycemic control, liver enzyme deviations, and lipid profiles improved after 24 weeks. Regarding indices for ß-cell function, changes in HOMA2-ß as well as DI, reflecting the ability of ß-cells to compensate for insulin resistance, were significantly higher in the semaglutide group compared with the DPP-4i group (mean change, +10.4 vs +0.6 in HOMA2-ß [P = .001] and +0.09 vs 0.0 in DI [P < .001]). Improvement in DI in the semaglutide group was correlated significantly to changes in body mass index (BMI), HbA1c, and fatty liver index reflecting liver steatosis. Multiple linear regression analysis revealed that dose of semaglutide (≥â¯7â mg/day), reduction in fatty liver index, and metformin nonuse were independently associated with improvement of DI. CONCLUSION: Switching to oral semaglutide ameliorated ß-cell function compared with DPP-4is, presumably via tissue-to-tissue crosstalk between liver and ß-cells.
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AIMS/INTRODUCTION: Few studies have investigated the renoprotective effect of glucagon-like peptide-1 (GLP-1) receptor in patients with chronic kidney disease (CKD). This study evaluated the effect of dulaglutide 0.75 mg on renal function in Japanese patients with type 2 diabetes and CKD stage 3 to 4. MATERIALS AND METHODS: Dulaglutide (group A) and non-dulaglutide (group B) were compared using data collected from a computerized diabetes care database. For group B, propensity score weighting based on propensity scores was performed. Evaluation items were a change from baseline in hemoglobin A1c (HbA1c), body weight, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), for 3 years. RESULTS: In total, the data obtained from 255 patients (125 and 130 patients for group A and B, respectively) were analyzed. Propensity score-adjusted patient background characteristics (group A vs B) were age 70.8 vs 69.4 years, body weight 70.2 vs 72.9 kg, body mass index 27.3 vs 28.1 kg/m2 , HbA1c 8.4 vs 8.5%, eGFR 47.9 vs 47.7 mL/min/1.73 m2 , and UACR 218 vs 251 mg/gCr. Although there were no statistically significant differences in the change from baseline between groups A and B at most time points in eGFR, a statistically significant eGFR decline in group B was observed in slope analysis for 3 years. This renoprotective effect was marked in patients with macro-albuminuria and/or concomitant SGLT2 inhibitor use. CONCLUSIONS: Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hemoglobina Glucada , Japón , Hipoglucemiantes/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Peso CorporalRESUMEN
Introduction: The use of a simple diagnostic system for nonalcoholic fatty liver disease (NAFLD) instead of a biopsy is expected. We investigated a positive pattern recognition system for the evaluation of nonalcoholic fatty liver (NAFL) and the stages of nonalcoholic steatohepatitis (NASH). Methods: A total of 68 Japanese patients with biopsy-confirmed NAFLD were enrolled. Serological biomarkers and medical imaging markers were investigated to determine candidate markers. The markers were statistically evaluated, and the patients were distributed to pattern combinations. Results: We selected three markers based on natural history and set the critical values: alanine aminotransferase/ALT (persistent ⧠44 IU/L) as a marker for hepatitis, type IV collagen 7S (â§5.1 ng/mL) for fibrosis, and E value (â§5.5 kPa) for stiffness. After evaluation of statistical accuracies, every patient was classified into their combination patterns. Comparing the relationships between histological classifications and positive patterns, the patients with NAFL were mainly distributed in pattern (ALT, type IV collagen, E value: -, -, -), those with NASH stage 0-1 in (+, -, +), those with NASH stage 2-3 in (+, +, +), and those with NASH stage 4 in (-, +, +). Conclusions: The positive patters changed with the NAFL and NASH conditions. Our results indicated a correlation between the positive patterns using three markers and the histological results. The positive pattern recognition system based on natural history is useful for the differential diagnosis of NAFLD and for the evaluation of the severity of fibrosis in patients with NASH.
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We aimed to analyze the association between dietary iron intake and obesity assessed by BMI after adjustment for nutrient intake (macronutrients and fiber) and food groups. The study design was cross-sectional. Patients with type-2 diabetes (n = 1567; 63.1% males; mean age 62.3 ± 11.6 years) were included in the study. To assess diet, consumption of typical food groups was determined by a food frequency questionnaire. Obesity was defined as BMI ≥ 25 kg/m2. We performed a binary regression analysis between quartiles of iron intake and obesity by quartiles of age group. A direct linear association was found for the highest quartile of iron intake and obesity in the younger age group of 30 to 54 years (OR = 3.641, 95% CI = 1.020-12.990; p trend = 0.011). Multivariate analysis using food groups as opposed to nutrients revealed a positive trend for obesity in the younger age group after adjusting for lifestyle factors, energy intake and bean and vegetable intake (p trend = 0.023). In all participants, an inverse association was observed before adjustment by vegetable intake (OR = 0.453, 95% CI = 0.300-0.684; p trend = 0.001). Higher iron intake was associated with obesity independent of macronutrient and fiber intake but only in the youngest quartile of age group examined.
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Diabetes Mellitus Tipo 2/complicaciones , Hierro de la Dieta/administración & dosificación , Obesidad/epidemiología , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Estudios Transversales , Dieta , Fibras de la Dieta/administración & dosificación , Ingestión de Alimentos , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Incretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on glycaemic and weight control, but little evidence has been published for the superiority of semaglutide for glycaemic control in patients after switching from a dipeptidyl peptidase-4 (DPP-4) inhibitor. Therefore, we aim to verify the efficacy of oral semaglutide in patients with T2D being treated with a DPP-4 inhibitor. METHODS AND ANALYSIS: This study is a multicentre, prospective, randomised, open-label, parallel-group trial. In total, 172 participants with T2D who have been treated with a DPP-4 inhibitor for more than 12 weeks and who have a glycated haemoglobin (HbA1c) level of 7.0%-9.9% will be randomised to continue using their existing DPP-4 inhibitor or switch to oral semaglutide for 24 weeks. Biochemical analyses and physical assessment will be performed, and adverse events will be recorded at baseline and at the end of the study. The primary endpoint will be the effect of oral semaglutide on the change in HbA1c. The secondary endpoints will be the mean changes in body weight, abdominal circumference, systolic and diastolic blood pressure (BP), pulse rate, the relationship between improvement of metabolic parameters including HbA1c and patient background characteristics, side effects and other laboratory parameters. ETHICS AND DISSEMINATION: This will be the first study to compare the effects of switching from a DPP-4 inhibitor to oral semaglutide on glycaemic control in patients with T2D. The results will be disseminated in peer-reviewed journals and at scientific conferences. Hokkaido University Certified Review Board (CRB no.1180001) has approved the protocol (no. 020-013). TRIAL REGISTRATION NUMBER: UMIN000045270 in the University Hospital Medical Information Network; jRCT1011210032 in the Japan Registry of Clinical Trials.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/uso terapéutico , Péptidos Similares al Glucagón , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
AIMS: Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, was shown to ameliorate lipid abnormalities in a phase III clinical trial of patients with type 2 diabetes mellitus (T2DM). However, its efficacy has not been demonstrated in real-world clinical practice in patients with T2DM. METHODS: We performed a multi-center prospective observational study of the use of pemafibrate in patients with T2DM and hypertriglyceridemia versus conventional therapy, with or without a fibrate. The primary outcomes were the changes from baseline in fasting serum triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations at week 52. RESULTS: We recruited 650 patients, and data from 504 (252 per group) were analyzed after propensity score matching. In the pemafibrate group, both TG and HDL-C showed significant improvements (p < 0.001), and several indices reflecting TG-rich lipoproteins, low-density lipoprotein-cholesterol particle size, and liver enzyme elevations were significantly ameliorated compared with the control group, but there was no difference in glycemic control markers. One of the key secondary endpoints showed that switching from conventional fibrates to pemafibrate improved eGFR but increased uric acid concentration. CONCLUSIONS: In patients with T2DM, pemafibrate has superior effects on lipid profile as well as liver and renal dysfunction to conventional fibrates.
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Diabetes Mellitus Tipo 2 , Hiperlipidemias , Hipertrigliceridemia , Humanos , Metabolismo de los Lípidos , Diabetes Mellitus Tipo 2/complicaciones , PPAR alfa/uso terapéutico , Butiratos/uso terapéutico , Butiratos/farmacología , Hipertrigliceridemia/tratamiento farmacológico , Hipertrigliceridemia/inducido químicamente , Hipertrigliceridemia/complicaciones , Triglicéridos , HDL-Colesterol , Ácidos Fíbricos/uso terapéuticoRESUMEN
BACKGROUND: We investigated the association between various food groups and obesity in Japanese patients with type 2 diabetes. METHODS: 2070 patients with type 2 diabetes who attended 26 diabetes clinics throughout Japan were analyzed and were divided into obese and non-obese groups. Intakes of food groups determined by a food frequency questionnaire were compared. Odds ratios for obesity for quartiles of individual food groups were calculated using a logistic regression model. RESULTS: Non-obese patients consumed a larger variety of food groups than obese patients, with the diets of non-obese individuals closer to the traditional Japanese diet characterized by fish, seaweed, and soybeans/soy products. Among 21 food groups, low vegetable intake and high sweets intake were the most strongly associated with obesity in both men and women. Low intake of both fruits and vegetables and the combination of high intake of sweets and low intake of fruits were associated with obesity. CONCLUSIONS: Food groups and their combinations that were strongly associated with obesity in Japanese patients with type 2 diabetes were identified. Our findings also suggested an inverse association between the traditional Japanese diet and obesity.
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Diabetes Mellitus Tipo 2 , Manejo de Datos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Dieta , Femenino , Frutas , Humanos , Japón/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Encuestas y Cuestionarios , VerdurasRESUMEN
AIMS: Sodium-glucose cotransporter-2 inhibitor (SGLT2i) reduces clinic blood pressure (BP), but the effects on BP circadian rhythm remain unclear. The present study aimed to determine the nighttime antihypertensive effect of SGLT2i compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) in patients with type 2 diabetes and hypertension. MATERIALS AND METHODS: In this randomized, open-label, parallel-group trial, patients treated with DPP-4i were either switched to luseogliflozin 2.5 mg/day (Luseo group;n = 30) or continued DPP-4i (DPP-4i group;n = 26). The patients undertook 24-h ambulatory BP monitoring before and 8 weeks after the group allocation. The primary endpoint was mean change in nighttime systolic BP (SBP). RESULTS: Nighttime SBP, as well as daytime SBP, was significantly reduced in the Luseo group compared with the DPP-4i group (nighttime, -4.0 ± 11.4 vs. 3.6 ± 10.7 mmHg,P = 0.01; daytime, -4.4 ± 10.9 vs. 3.7 ± 11.9 mmHg,P = 0.01). Similarly, nighttimepulse rate(PR) was significantly reduced in the Luseo group (-2.0 ± 4.8 vs. 0.9 ± 4.8 bpm,P = 0.03). The proportion of patients with abnormal BP circadian rhythms (non-dipper pattern plus riser pattern) was significantly lower in the Luseo group (36.6% vs. 56.7%,P < 0.05). CONCLUSIONS: Switching from DPP-4i to luseogliflozin decreased nighttime SBP and PR; moreover, BP circadian rhythm was improved.
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Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Hipertensión , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Ritmo Circadiano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Frecuencia Cardíaca , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Estudios Prospectivos , Sorbitol/análogos & derivadosRESUMEN
To investigate the association between dietary energy density (DED) and obesity in people with type 2 diabetes mellitus. Moreover, we compared the strength of the associations of DED with intake of energy and macronutrients in terms of obesity as well as nutritional factors that have long been used for medical nutritional therapy. Cross-sectionally investigated were 1615 outpatients with type 2 diabetes who attended 26 clinics nationwide with diabetes specialists. Odds ratios (ORs) were calculated for the association between obesity and DED, energy, and macronutrients by quintile categories and a 1 SD increment with adjustment for potential confounders. ß coefficients were calculated for the association between body mass index (BMI) and each nutritional factor by 1 SD increments in nutritional values. Multi-adjusted OR for obesity between extreme quintiles of DED was 2.99 (95% confidence interval (95% CI): 2.01-3.12). Conversely, the ORs did not differ significantly according to the quintiles of other nutrient factors. Multi-adjusted ß coefficient of BMI per 1 SD according to DED was far higher than those of other nutrient factors (ß coefficient 0.65, 95% CI: 0.41-0.88). These findings indicated that DED in persons with type 2 diabetes was positively associated with BMI and the prevalence of obesity. DED was also much more potently associated with obesity and BMI than nutritional indicators such as intake of energy or macronutrients.
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Diabetes Mellitus Tipo 2/fisiopatología , Ingestión de Alimentos , Ingestión de Energía , Valor Nutritivo , Obesidad/fisiopatología , Anciano , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Dieta/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nutrientes/análisis , Obesidad/complicaciones , Obesidad/epidemiología , Oportunidad Relativa , PrevalenciaRESUMEN
INTRODUCTION: Glucagon-like peptide (GLP)-1 receptor agonists exert potent hypoglycemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent manner. Once-weekly subcutaneous administration of the GLP-1 receptor agonist semaglutide has beneficial effects on glycemic and body weight control, but it is currently unclear if semaglutide provides superior glycemic control compared to conventional GLP-1 receptor agonists in the Japanese population. We aim to compare the effects of once-weekly subcutaneous semaglutide with those of liraglutide or dulaglutide administration in Japanese patients with T2D. METHODS: This study is a multicenter, prospective, randomized, open-label, blinded-endpoint, parallel-group trial. In total, 100 participants with T2D who have been treated with liraglutide (0.9-1.8 mg/day in plan A) or dulaglutide (0.75 mg/week in plan B) for more than 12 weeks and have a glycated hemoglobin (HbA1c) level of 6.0-9.9% and a body mass index (BMI) of ≥ 22 kg/m2 will be randomized to either continue using their existing GLP-1 receptor agonist or switch to subcutaneous semaglutide once weekly for 24 weeks. Biochemical analysis, physical assessment, and a quality-of-life questionnaire (DTSQ) will be completed at baseline and at the end of the study. The primary endpoint is the effect of semaglutide on the change in HbA1c. The secondary endpoints are the mean changes in total DTSQ score, body mass, abdominal circumference, systolic and diastolic blood pressure, pulse rate, factors associated with improvement in HbA1c and secondary endpoints, side effects, and other laboratory parameters. PLANNED OUTCOMES: The results of the study will provide useful information regarding the effects of switching to semaglutide from other GLP-1 receptor agonists on glycemic control in patients with T2D. ETHICS AND DISSEMINATION: The Hokkaido University Certified Review Board (CRB no. 1180001) has approved the protocol (no. 018-005). The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION: UMIN000042369 in the University Hospital Medical Information Network (UMIN); jRCT1011200008 in the Japan Registry of Clinical Trials (jRCT); pre-results.
RESUMEN
AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors, as well as thiazolidines, suppress nonalcoholic fatty liver disease (NAFLD); however, few comparative studies have been reported. Dapagliflozin has shown non-inferiority compared with pioglitazone for glycemic control, and superiority regarding weight reduction in patients with type 2 diabetes. We carried out a secondary analysis for the favorable effects of sodium-glucose cotransporter inhibitors for NAFLD. MATERIALS AND METHODS: In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, patients taking pioglitazone for ≥12 weeks were randomly switched to dapagliflozin or continued pioglitazone for a further 24 weeks. The fatty liver index (FLI), consisting of body mass index, triglycerides, waist circumference and γ-glutamyl transpeptidase, was used for the evaluation of NAFLD. RESULTS: A total of 53 participants with NAFLD (27 dapagliflozin; 26 pioglitazone) were included in this analysis. FLI decreased significantly in the dapagliflozin group (48.7 ± 23.4 to 42.1 ± 23.9) compared with the pioglitazone group (49.0 ± 26.1 to 51.1 ± 25.8; P < 0.01). Multiple linear regression analysis showed that the changes in FLI had a significantly positive correlation with changes in glycated hemoglobin (P = 0.03) and insulin level (P < 0.01) in the dapagliflozin group. CONCLUSION: Dapagliflozin might be more beneficial than pioglitazone in patients with NAFLD. Improvements in FLI would be closely related to glycemic control.
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Compuestos de Bencidrilo/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/farmacología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Pioglitazona/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Anciano , Glucemia/efectos de los fármacos , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Hemoglobina Glucada/efectos de los fármacos , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/etiología , Estudios Prospectivos , Resultado del Tratamiento , Triglicéridos/sangre , Circunferencia de la Cintura/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos , gamma-Glutamiltransferasa/sangreRESUMEN
AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are used worldwide because of their multiple benefits for patients with type 2 diabetes. The purpose of this study was to determine the efficacy and safety of SGLT2i in patients with type 1 diabetes. MATERIALS AND METHODS: Patients with type 1 diabetes who had been treated with SGLT2i for >12 weeks were included in this retrospective observation study. We recorded the changes in body mass, insulin dose, blood and urine test data, and adverse events. The changes in day-to-day glucose variability, as the primary end-point, was evaluated using the interquartile range (P25/P75) of the ambulatory glucose data obtained using continuous glucose monitoring. RESULTS: A total of 51 patients (37 women; mean age 52.7 years) were included. Glycated hemoglobin and body mass significantly decreased by 0.4% and 1.6 kg, respectively. The total required insulin dose decreased by 9.4% (42.7 ± 26.6-38.7 ± 24.3 units/day). Continuous glucose monitoring data were obtained from 30 patients. P25/P75 decreased by 17.6 ± 20.7% during SGLT2i treatment (P < 0.001). The percentage of time per day within the target glucose range of 70-180 mg/dL significantly increased (from 42.2 to 55.5%, P < 0.001), without an increase in the percentage of time spent in the hypoglycemic range (<70 mg/dL). Urinary ketone bodies were detected in four patients (7.8%), but none developed ketoacidosis. CONCLUSIONS: SGLT2i improved day-to-day glucose variability and time in the target glucose range, without increasing frequency of hypoglycemia, in patients with type 1 diabetes, and reduced glycated hemoglobin, body mass and the required insulin dose.
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Biomarcadores/metabolismo , Glucemia/análisis , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
AIMS/INTRODUCTION: To identify the effect of combination therapy with a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter 2 inhibitor compared with switching from a dipeptidyl peptidase-4 inhibitor to a sodium-glucose cotransporter 2 inhibitor on improving the glucose variability in patients with or without impaired endogenous insulin secretion. MATERIALS AND METHODS: A secondary analysis regarding the relationship between endogenous insulin secretion and the change in mean amplitude of glycemic excursions (ΔMAGE) was carried out in a multicenter, prospective, randomized, parallel-group comparison trial that enrolled patients with type 2 diabetes who had been taking teneligliptin and were treated by switching to canagliflozin (SWITCH) or adding canagliflozin (COMB). Participants were categorized into the following four subgroups: SWITCH or COMB and high or low fasting C-peptide (CPR) divided at baseline by the median. RESULTS: ΔMAGE in the COMB group was greatly improved independent of a high or low CPR (-29.2 ± 28.3 vs -20.0 ± 24.6, respectively; P = 0.60). However, ΔMAGE was not ameliorated in the low CPR SWITCH group, and the ΔMAGE was significantly smaller than that in the high CPR COMB group (P < 0.01). CONCLUSIONS: COMB would be a better protocol rather than switching teneligliptin to canagliflozin to improve daily glucose variability in patients with impaired endogenous insulin secretion.