Liraglutide Versus Sitagliptin in a 24-week, Multicenter, Open-label, Randomized, Parallel-group Study in Japanese Type 2 Diabetes Mellitus Patients Responding Inadequately to a Sulfonylurea and/or One or Two Other Oral Antidiabetic Drugs (JDDM 33)
PubMed | Kaiseikai Tsutsumi Hospital, HEC Science Clinic, Oishi Clinic, Yagi Medical Clinic and 4 more.
Type: | Journal: Japanese clinical medicine | Year: 2014
Liraglutide (glucagon-like peptide-1 [GLP-1] receptor agonist) and sitagliptin (dipeptidyl peptidase-4 inhibitor) are approved in Japan for treating type 2 diabetes mellitus (T2DM). We compared the efficacy and safety of adding liraglutide or sitagliptin to a sulfonylurea in Japanese T2DM patients.Patients aged 18 to <80 years with hemoglobin A1c (HbA1c; National Glycohemoglobin Standardization Program [NGSP]) of 6.9-9.4%, body mass index 35 kg/m(2), and treatment with a sulfonylurea and/or one or two non-sulfonylurea oral antidiabetic drugs for greater than or equal to eight weeks before enrollment were eligible. Patients were randomized in an open-label manner to either 0.9 mg/day liraglutide (n = 50) or 50-100 mg/day sitagliptin (n = 49) and were treated for 24 weeks. Non-sulfonylureas were discontinued before randomization. Patients using other oral antidiabetic drugs started sulfonylurea treatment. The primary endpoint was the change in HbA1c from baseline to Week 24.HbA1c decreased in both groups, and the reduction was significantly greater throughout in the liraglutide group except for Week 24 (0.59 0.80 vs. 0.24 0.94%; P = 0.0525). Fasting plasma glucose (FPG) decreased significantly in the liraglutide group compared with the sitagliptin group (-21.15 31.22 vs. +0.46 39.39 mg/dL; P = 0.0014). Homeostasis model assessment of cell function and C-peptide increased significantly in the liraglutide group but not in the sitagliptin group. Hypoglycemic symptoms and adverse events occurred in four and nine patients, respectively, in the liraglutide group, and in two and five patients, respectively, in the sitagliptin group.Treatment with liraglutide or sitagliptin together with a sulfonylurea improved HbA1c in Japanese T2DM patients in primary care. Both drugs were associated with low rates of adverse events and hypoglycemia. The improvement in cell function probably contributed to the improvement in glycemic control in the liraglutide group.
Oishi M.,Oishi Clinic |
Yamazaki K.,Kawai Clinic |
Okuguchi F.,Okuguchi Clinic |
Sugimoto H.,Sugimoto Clinic |
And 2 more authors.
Journal of Diabetes Investigation | Year: 2014
Aims/Introduction: Six kinds of oral antidiabetic drugs (OADs), including the new dipeptidyl peptidase 4 (DPP-4) inhibitors, are available. The present study aimed to define trends within the prescribing patterns of OADs, as well as changes in glycemic control in Japan over a 10-year period from 2002 to 2011. Materials and Methods: We carried out a cross-sectional study using data of type 2 diabetes mellitus patients from 24 clinics for 2002, 2005, 2008 and 2011. OAD use was analyzed combined with clinical data. Results: Sulfonylureas (SUs) were the most commonly used OAD, but their use for monotherapy markedly decreased over the study period. Biguanides (BGs) were the second most commonly used OAD, and their prescribing rate increased both for mono- and combination therapy. DPP-4 inhibitors (DPP-4I), released in 2009, were the third most commonly prescribed OAD in 2011 both for mono- and combination therapy. Among combination therapies, two OADs were mostly prescribed, but the use of three OADs and four OADs in 2011 was two- and 14.8-fold those in 2002. These trends were accompanied by an improvement in average glycated hemoglobin from 7.5 ± 1.2% in 2002 to 7.1 ± 0.9% in 2011. Conclusions: The OAD prescribing trend has moved away from monotherapy with SUs and toward combination therapies to achieve better glycemic control. Increased use of BGs and DPP-4I was predominant in 2011. These trends were accompanied by an improvement of the glycated hemoglobin level. © 2013 The Authors.
Satoh-Asahara N.,National Hospital Organization Kyoto Medical Center |
Kotani K.,National Hospital Organization Kyoto Medical Center |
Kotani K.,Jichi Medical University |
Yamakage H.,National Hospital Organization Kyoto Medical Center |
And 6 more authors.
Atherosclerosis | Year: 2015
Objective: The cardio-ankle vascular index (CAVI) is an index of arterial stiffness less dependent on blood pressure and an indicator suitable for assessing the arterial dysfunction. However, it remains unclear whether CAVI can predict the outcome of cardiovascular diseases (CVD) in obese patients. Methods: A total of 425 obese Japanese outpatients (189 men and 236 women, mean age: 51.5 years) were enrolled in a multicenter prospective cohort Japan, the Japan Obesity and Metabolic Syndrome Study (JOMS). Primary analysis regarding measurements of cardiovascular risk factors including CAVI and the occurrence of macrovascular complications was based on following the participants over a 5-year period. Results: Of the eligible patients, 300 (78%) were followed into the fifth year. During the study period, 15 coronary heart disease, 7 stroke, and 6 arteriosclerosis obliterans events occurred. All events occurred in 28 patients, and CVD incidence rate was 15.8 per 1000 person-years. In the analysis of adjusted models for traditional risk factors, CAVI was a significant factor for the incidence of events. In addition, high CAVI and low HDL-cholesterol were significant factors for the incidence of events in Cox stepwise multivariate analysis when age- and sex-adjusted (CAVI [per 1]: HR = 1.44 [1.02-2.02], p = 0.037; HDL-cholesterol [per 1 mmol/L]: HR = 0.20 [0.06-0.69], p = 0.011). In addition, CAVI added value to atherosclerotic cardiovascular disease risk score in predicting the development of CVD. Conclusion: This study demonstrates for the first time that CAVI is an effective predictor of CVD events in obese patients. © 2015 Elsevier Ireland Ltd.
Yokoyama H.,Jiyugaoka Medical Clinic |
Araki S.,Shiga University of Medical Science |
Haneda M.,Asahikawa University |
Matsushima M.,Jikei University School of Medicine |
And 7 more authors.
Diabetologia | Year: 2012
Aims/hypothesis: In type 2 diabetic patients at low risk for cardiovascular disease (CVD), the relationship between the clinical course of nephropathy by stage of chronic kidney disease (CKD) and onset of CVD remains unclear. Clarification of this relationship is important for clinical decision-making for both low-and high-risk diabetic patients. Methods: This 4 year prospective study enrolled 2,954 type 2 diabetic patients with no prevalent CVD, and serum creatinine <176.8 μmol/l. The risk for CVD onset (non-fatal and fatal CVD and stroke, and peripheral arterial disease) was assessed according to CKD stage categorised by urinary albumin-to-creatinine ratio (ACR; mg/mmol) and estimated GFR (eGFR; ml min-1 1.73 m-2). Association of progression from žno CKD' stage (ACR <3.5 mg/mmol and eGFR ≥90 ml min 1.73 m-2) with risk for CVD onset was also evaluated. Results: During follow-up (median 3.8 years), 89 CVD events occurred. Compared with patients with žno CKD' as reference, those with ACR≥35.0 mg/mmol with coexisting eGFR 60-89 ml min-1 1.73 m-2 or <60 ml min-1 1.73 m-2 showed increased risk for CVD onset, whereas those with eGFR ≥90 ml min1- 1.73 m-2 did not. Those with ACR ≤3.5 mg/mmol and eGFR ≤60 ml min-1 1.73 m -2 did not show any increased risk. Among patients with žno CKD' stage at baseline, those who progressed to ACR ≥3.5 mg/mmol during follow-up showed an increased risk compared with those who did not, whereas those who progressed to eGFR ≥90 ml min-1 1.73 m-2 did not have increased risk. Conclusions/interpretation: The risk for CVD was associated with progression of albuminuria stage rather than eGFR stage in type 2 diabetic patients at relatively low risk for CVD. © Springer-Verlag 2012.
Satoh-Asahara N.,National Hospital Organization |
Satoh-Asahara N.,Diabetes Center |
Suganami T.,Tokyo Medical and Dental University |
Majima T.,National Hospital Organization |
And 16 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011
Background and Objectives: Obesity and metabolic syndrome (MS) increase the risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and all-cause mortality. Serum cystatin C (S-CysC), a marker of GFR, has been shown to be associated with CVD and CKD. This study was designed to elucidate the association of urinary CysC (U-CysC), a marker of renal tubular dysfunction, with CVD and CKD risk factors in patients with obesity and MS. Design, setting, participants, & measurements: The U-CysC-creatinine ratio (UCCR) was examined in 343 Japanese obese outpatients enrolled in the multi-centered Japan Obesity and Metabolic Syndrome Study. Results: UCCR was positively correlated with urine albumin-creatinine ratio (UACR) and S-CysC and negatively correlated with estimated GFR (eGFR). Among obese patients, UCCR was significantly higher in MS patients than in non-MS patients. UCCR had significant correlations with the number of components of MS and arterial stiffness, all of which are CVD predictors, similarly to UACR (P < 0.05). Interestingly, diet- and exercise-induced weight reduction for 3 months significantly decreased only UCCR among all of the renal markers examined (P < 0.01), in parallel with the decrease in BMI, HbA1c, and arterial stiffness, suggesting the beneficial effect of weight reduction on renal tubular dysfunction. Conclusions: This study demonstrates that UCCR is significantly associated with renal dysfunction, the severity of MS, arterial stiffness, and weight change in obese patients. The data of this study suggest that UCysC could serve as a CVD and CKD risk factor in patients with obesity and MS. Copyright © 2011 by the American Society of Nephrology.
Observational 6-month open-label study of Japanese type 2 diabetes patients switching from NPH insulin to insulin detemir in basal-bolus regimen: 23rd article of the Japan diabetes clinical data management study group (JDDM23)
Oishi M.,Oishi Clinic |
Abe N.,Abe Diabetes Clinic |
Yokoyama H.,Jiyugaoka Yokoyama Internal Medicine Clinic |
Kuribayashi N.,Misaki Internal Medicine Clinic |
And 3 more authors.
Journal of International Medical Research | Year: 2012
OBJECTIVE: Glycaemic control is critical to prevent diabetic complications and mortality. This 6-month, open-label, observational study assessed the efficacy and safety of switching Japanese patients with type 2 diabetes from neutral protamine Hagedorn (NPH) insulin to insulin detemir. METHODS: Patients with type 2 diabetes (n = 126) receiving basal-bolus insulin therapy with NPH insulin plus rapid-acting insulin analogues were recruited. NPH insulin was replaced with insulin detemir for 6 months. Glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), daily glucose levels and hypoglycaemia were monitored. Nocturnal quality of life was assessed by insulin therapy related quality of life at night questionnaire. RESULTS: HbA1c, FPG and body weight were all significantly reduced after treatment with insulin detemir for 6 months, without increasing severe hypoglycaemia. Insulin dose increased significantly over the same time. There were significant improvements in overall nocturnal quality of life, as well as well-being. CONCLUSIONS: Treatment with insulin detemir for 6 months resulted in substantial benefits, including reduced HbA1c, FPG and body weight, and improvements in nocturnal quality of life, without increasing hypoglycaemia. © 2012 Field House Publishing LLP.
Yokoyama H.,Jiyugaoka Medical Clinic |
Matsushima M.,Jikei University School of Medicine |
Kawai K.,Kawai Clinic |
Hirao K.,HEC Science Clinic |
And 6 more authors.
Diabetic Medicine | Year: 2011
Aims To investigate whether a reduced incidence of cardiovascular disease in Type2 diabetes can be achieved in a newly recruited cohort following the recently advanced concept of multifactorial treatment and followed in primary care settings as compared with earlier cohorts. Methods A prospective study was performed in primary care settings at multiple clinics nationwide in the Japan Diabetes Clinical Data Management (JDDM) study group. Subjects were 2984 patients with Type2 diabetes without prevalent cardiovascular disease. The main outcome measure was the first event of non-fatal or fatal coronary heart disease, ischaemic stroke or peripheral artery disease, and the incidence was compared with other representative cohorts. Results There were 90 cardiovascular events over 10827 person-years of follow-up with a dropout rate of 6%. The incidences (per 1000 person-years, 95% confidence interval) of composite, coronary heart disease, ischaemic stroke and peripheral artery disease in the JDDM study were 8.3 (6.6-10.0), 4.4 (3.2-5.6), 3.1 (2.1-4.2), and 0.7 (0.2-1.2), respectively. Each incidence was lowest in the JDDM study compared with other cohorts (P<0.01 vs. each cohort). In the JDDM study, significant variables predictive of the occurrence of a cardiovascular event were age, duration of diabetes, HbA 1c, HDL cholesterol and urinary albumin. Conclusion The novel finding of low cardiovascular disease occurrence in this study may be conferred by the feasibility at primary care settings for providing patients with Type2 diabetes with favourable control of blood glucose, blood pressure and lipids, coupled with unique ethnicity/country factors. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.
PubMed | HEC Science Clinic, Oishi Clinic, Kurihara Clinic, Shiga University of Medical Science and 5 more.
Type: Journal Article | Journal: BMJ open diabetes research & care | Year: 2016
The fact that population with type 2 diabetes mellitus and bodyweight of patients are increasing but diabetes care is improving makes it important to explore the up-to-date rates of achieving treatment targets and prevalence of complications. We investigated the prevalence of microvascular/macrovascular complications and rates of achieving treatment targets through a large-scale multicenter-based cohort.A cross-sectional nationwide survey was performed on 9956 subjects with type 2 diabetes mellitus who consecutively attended primary care clinics. The prevalence of nephropathy, retinopathy, neuropathy, and macrovascular complications and rates of achieving targets of glycated hemoglobin (HbA1c) <7.0%, blood pressure <130/80mmHg, and lipids of low-density/high-density lipoprotein cholesterol <3.1/1.0mmol/L and non-high-density lipoprotein cholesterol <3.8mmol/L were investigated.The rates of achieving targets for HbA1c, blood pressure, and lipids were 52.9%, 46.8% and 65.5%, respectively. The prevalence of microvascular complications was 28% each, 6.4% of which had all microvascular complications, while that of macrovascular complications was 12.6%. With an increasing duration of diabetes, the rate of achieving target HbA1c decreased and the prevalence of each complication increased despite increased use of diabetes medication. The prevalence of each complication decreased according to the number achieving the 3 treatment targets and was lower in subjects without macrovascular complications than those with. Adjustments for considerable covariates exhibited that each complication was closely inter-related, and the achievement of each target was significantly associated with being free of each complication.Almost half of the subjects examined did not meet the recommended targets. The risk of each complication was significantly affected by 1 on-target treatment (inversely) and the concomitance of another complication (directly). Total diabetes care including one-by-one management of modifiable risk factors and complications may be important for high-quality care. The future studies including more subjects and clinics with precise complication status are needed.
PubMed | HEC Science Clinic, Oishi Clinic, Shiga University of Medical Science, Niigata University and 3 more.
Type: Journal Article | Journal: Diabetes research and clinical practice | Year: 2015
The protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting.A six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed.Baseline use of pioglitazone (n=493) did not show a statistically protective effect on the primary endpoint (n=175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43-1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33-0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare.This observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy.
PubMed | Oishi Clinic, National Hospital Organization Kyoto Medical Center, Jichi Medical University, National Hospital Organization Mie Hospital and 2 more.
Type: Journal Article | Journal: Atherosclerosis | Year: 2015
The cardio-ankle vascular index (CAVI) is an index of arterial stiffness less dependent on blood pressure and an indicator suitable for assessing the arterial dysfunction. However, it remains unclear whether CAVI can predict the outcome of cardiovascular diseases (CVD) in obese patients.A total of 425 obese Japanese outpatients (189 men and 236 women, mean age: 51.5 years) were enrolled in a multicenter prospective cohort Japan, the Japan Obesity and Metabolic Syndrome Study (JOMS). Primary analysis regarding measurements of cardiovascular risk factors including CAVI and the occurrence of macrovascular complications was based on following the participants over a 5-year period.Of the eligible patients, 300 (78%) were followed into the fifth year. During the study period, 15 coronary heart disease, 7 stroke, and 6 arteriosclerosis obliterans events occurred. All events occurred in 28 patients, and CVD incidence rate was 15.8 per 1000 person-years. In the analysis of adjusted models for traditional risk factors, CAVI was a significant factor for the incidence of events. In addition, high CAVI and low HDL-cholesterol were significant factors for the incidence of events in Cox stepwise multivariate analysis when age- and sex-adjusted (CAVI [per 1]: HR = 1.44 [1.02-2.02], p = 0.037; HDL-cholesterol [per 1 mmol/L]: HR = 0.20 [0.06-0.69], p = 0.011). In addition, CAVI added value to atherosclerotic cardiovascular disease risk score in predicting the development of CVD.This study demonstrates for the first time that CAVI is an effective predictor of CVD events in obese patients.