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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

Aims/Introduction Glinides are antidiabetic drugs that enhance the early phase of insulin secretion, but have been considered to be less effective at lowering blood glucose than sulfonylureas. However, glinides show a lower risk of hypoglycemia and a greater effect on postprandial hyperglycemia, and are particularly recommended for use in elderly patients with type 2 diabetes. We investigated the efficacy and safety of repaglinide compared with sulfonylurea for the treatment of elderly patients. Materials and Methods In the present multicenter, prospective, randomized, open‐label, controlled trial, 57 elderly lean patients with type 2 diabetes who were being treated with sulfonylureas were studied. They were either switched to repaglinide (Repa group) or continued a sulfonylurea (SU group) for 12 weeks. The primary outcome comprised the change in glycemic control, and among the secondary outcomes was the presence of hypoglycemia and drug compliance. Results Although glycated hemoglobin (HbA1c) was not significantly different between the two groups (SU +0.02% vs Repa −0.07%), greater improvements in the glycated albumin (GA) and GA to HbA1c ratio (GA/HbA1c) were observed in the Repa group (ΔGA, SU +0.12% vs Repa −1.15%; ΔGA/HbA1c, SU +0.01 vs Repa −0.13; each P

Introduction Pemafibrate is a potent selective peroxisome proliferator-activated receptor α (PPARα) modulator that may be safer than conventional PPARα agonists in the treatment of dyslipidemia. This study was designed to investigate the efficacy of low-dose pemafibrate (0.1 mg/day) therapy for hypertriglyceridemia in 31 patients with type 2 diabetes and high triglyceride (TG) levels at the Manda Memorial Hospital. Methods TG, remnant lipoprotein cholesterol (RLP-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI, Apo AII, Apo B, Apo CII, Apo CIII, and Apo E levels were evaluated. Liver, kidney, and muscle toxicity tests were also performed. Pemafibrate (0.1 mg) was administered once daily. Results This treatment significantly decreased TG, RLP-C, Apo CII, Apo CIII, and Apo E levels while significantly increasing HDL-C, Apo AI, and Apo AII levels. No significant changes were observed in LDL-C and Apo B levels. There were no significant liver-, kidney-, or muscle-related adverse events. Conclusions The results of this study show that low-dose pemafibrate administration improves the lipid profile in Japanese patients with hypertriglyceridemia and type 2 diabetes.

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.

We examined the feasibility of ultrasound diagnosis of insulin-derived localized amyloidosis (IDLA). In addition to ultrasound detectability and findings, the insulin absorption rate, insulin dosage and hemoglobin A1c (HbA1c) levels before and after shifting the insulin injection site were investigated for 22 cases of IDLA. The detectability of IDLA on ultrasound was 100%; 59.1% was palpable lumps and 40.9% was not palpable. The palpable type had lower echo intensity and were harder than the non-palpable type. Blood flow decreased in IDLA, especially in the palpable type. IDLA, especially the palpable type, had a low insulin absorption rate. HbA1c level and insulin dosage decreased after shifting the injection site. The palpable type had more insulin reduction than the non-palpable type. Characteristic ultrasound images of IDLA were acquired. As the non-palpable type could be identified by ultrasound, its diagnosis encourages changing the insulin injection site; hence, ultrasound diagnosis of IDLA can enhance insulin treatment.

Background: To explore the efficacy and safety of switching from once-daily basal insulin therapy to once-daily pre-meal injec -tion insulin degludec/insulin aspart (IDegAsp) with respect to the glycemic control of participants with type 2 diabetes mellitus (T2DM). Methods: In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, participants on basal insulin therapy were switched to IDegAsp (IDegAsp group; n=30) or continued basal insulin (Basal group; n=29). The primary end -point was the superiority of IDegAsp in causing changes in the daily blood glucose profile, especially post-prandial blood glucose concentration after 12 weeks. Results: Blood glucose concentrations after dinner and before bedtime were lower in the IDegAsp group, and the improvement in blood glucose before bedtime was significantly greater in the IDegAsp group than in the Basal group at 12 weeks (-1.7±3.0 mmol/L vs. 0.3±2.1 mmol/L, P

Incretin-related drugs, such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, have been clinically available and widely used to treat patients with type 2 diabetes mellitus. Accumulating evidence indicates that these agents exert glycemic control and have various other favorable effects, including prevention of atherosclerosis. It is important to assess and manage early-phase atherosclerosis, but whether diabetic therapeutics including incretin-related drugs improve or maintain vascular endothelial cell function has not been fully determined. We previously published prospective clinical trials focused on flow-mediated dilation in patients with type 2 diabetes, who did not have severe atherosclerosis, using two different incretin-related drugs: a DPP-4 inhibitor and a GLP-1 analogue. These trials showed that these therapeutic agents did not improve endothelial cell function. In this article, we discuss how incretin-related drugs contribute, if at all, to vascular endothelial cell function, atherosclerosis, and beta-cell function, based on our clinical trials and previous evidence.

Aims/Introduction We carried out an observational cohort study to examine the relationship between the efficacy of oral antidiabetic drugs and clinical features in type 2 diabetics. Materials and Methods We analyzed the CoDiC® database of the Japan Diabetes Data Management Study Group across 67 institutions in Japan. In a total of 3,698 drug‐naïve patients who were initiated with metformin, dipeptidyl peptidase‐4 inhibitor (DPP‐4i) or sulfonylurea (SU) from 2007 to 2012, we evaluated body mass index (BMI) and hemoglobin A1c (HbA1c). The patients were stratified according to their clinical features, and matched using a propensity score to adjust for baseline factors. Results HbA1c was reduced with all drugs, with the largest effect elicited by DPP‐4i and the smallest by SU (P = 0.00). HbA1c increased with SU after 6 months in the patients stratified by an age‐of‐onset of 25 (P = 0.00). The reduction in HbA1c was larger in patients with HbA1c of ≥8%, compared with that in patients with HbA1c of

Aims/Introduction We compared treatment satisfaction in type 2 diabetes patients taking daily and weekly glucagon‐like peptide‐1 receptor agonists. Materials and Methods The study was a 12‐week, multicenter, open‐label, prospective, randomized, parallel‐group comparison trial. The participants were Japanese patients with type 2 diabetes being administered with the glucagon‐like peptide‐1 receptor agonist, liraglutide, daily for >3 months. Patients were randomly assigned to either continue taking liraglutide once daily (Lira group) or switch to dulaglutide once weekly (Dula group). The primary outcome was the change in the Diabetes Treatment Satisfaction Questionnaire score from baseline to week 12 in the two groups. The secondary outcomes comprised changes in the Diabetes Therapy‐Related Quality of Life score, body mass and glycemic control. Results A total of 33 participants were initially enrolled in the trial, and 31 participants completed the protocol. The change in the Diabetes Treatment Satisfaction Questionnaire score in the Dula group was significantly greater than that in the Lira group (+0.1 ± 4.7 in the Lira group vs +4.9 ± 5.2 in the Dula group; P = 0.013). The change in Diabetes Therapy‐Related Quality of Life score in the Dula group was significantly greater than that in the Lira group (−3.7 ± 6.9 vs +8.9 ± 15.1; P = 0.007). There were no significant differences between groups in the changes in body mass, plasma glucose or glycated hemoglobin. Conclusions Weekly administration of dulaglutide was superior to liraglutide with regard to treatment satisfaction in patients with type 2 diabetes, in the absence of any negative effect on glycemic control.

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.

Aims We investigated the mechanism underlying body weight (BW) gain after pioglitazone administration in type 2 diabetes in relation to gender differences in abdominal fat distribution and congestive factors.

A 62-year-old man with type 2 diabetes mellitus, who had been on insulin therapy for the past 20 years, was found to have subcutaneous mass formation in the abdomen during a workup of worsened glycemic control. Because of suspected amyloid deposition, he was advised to avoid injections to the mass, which led to improvement of glycemic control. However, he strongly requested mass excision and was hospitalized. After evaluation using ultrasonography and computed tomography, a total mass excision was performed, and a diagnosis of insulin-derived amyloidosis was made. Comparison of the ultrasonographic and histopathological findings demonstrated that the location of the amyloid deposition nearly corresponded to the hypoechoic region. This case highlights that ultrasonography, which is a noninvasive imaging modality, can be useful for detection of insulin-derived amyloidosis.

DPP-4 inhibitors have been used to treat patients with type 2 diabetes mellitus. These agents not only provide glycemic control, but also have other favorable effects, including the prevention of atherosclerosis. However, it has not been determined whether these agents can improve or maintain endothelial cell function. We previously reported the results of two prospective studies assessing the effects of incretin agents on flow-mediated dilation in patients with type 2 diabetes mellitus without severe atherosclerotic diseases. These studies showed that both the DPP-4 inhibitor sitagliptin and the GLP-1 analogue liraglutide did not improve endothelial cell function. This report discusses the effects of sitagliptin on early-stage atherosclerosis and beta-cell function.

【目的】 糖尿病性腎症を基礎疾患とする血液透析患者では消化管運動機能低下により機能性ディスペプシア（functional dyspepsia；FD）が多く認められる．これに対し近年，漢方薬である六君子湯の有効性が報告されている．今回われわれは糖尿病性腎症を基礎疾患とする血液透析患者のFDに対する六君子湯の有効性を検討した．【方法】 対象は糖尿病性腎症を基礎疾患とする血液透析患者でFDと診断されオメプラゾール20 mg/日の6か月以上の投与が無効であった15名．文書同意を得た後，六君子湯投与前と投与4週間後に，FD症状の質問を加えたGSRS（gastrointestinal symptom rating scale），WHOQOL26の質問票を用いて，患者の消化器症状および生活全体のquality of life（QOL）を評価した．【結果・結論】 GSRSによる評価では，FDの症状だけでなく腹痛，酸逆流，消化不良，下痢，便秘全ての症状で有意な改善効果が認められた．WHOQOL26による評価では，心理学的領域および生活全般領域で有意なQOLの改善が認められた．また，血液検査による評価での総蛋白の有意な上昇と，心胸郭比の低下が認められ，栄養状態が改善された可能性があることが示唆された．六君子湯は，糖尿病性腎症を基礎疾患とした血液透析患者の，FDをはじめとする機能性消化管障害に対する安全かつ有効な治療の選択肢となり得ると考えられた．

The effectiveness of BIAsp 30 step-up therapy in achieving glycemic control in Japanese patients with type 2 diabetes mellitus was investigated. Study subjects were 99 patients with type 2 diabetes mellitus aged over 20 years who were judged to require insulin therapy due to poor glucose control (HbA1c level of ≥ 7.5%). BIAsp 30 dosage was determined by the patient's attending physician; coadministration of hypotensive agents and antilipemic agents was permitted, but OAD coadministration was limited to patients already receiving such drugs at the start of the study. Patients who did not achieve HbA1c < 6.5% after 16±5 weeks with QD (Phase 1) were stepped up to BID (Phase 2). If patients still had not achieved HbA1c < 6.5% after 16±5 weeks with BID, they were stepped up to TID (Phase 3). 55 of the 99 enrolled subjects completed the study and the rates of achievement of HbA1c < 6.5% and HbA1c < 7.0% were 45.5% and 74.5% respectively. Of all registered subjects, 5.1% (5/99) achieved HbA1c < 6.5% in QD, 19.5% (16/82) in BID, and 20.6% (7/34) in TID. Statistically significant reductions in HbA1c levels were recorded at the conclusion of each phase, with no incidents requiring intervention, indicating that BIAsp 30 step-up therapy is a safe, simple therapy that can be useful in achieving better glycemic control for Japanese patients with type 2 diabetes mellitus.

Recent studies have shown that posttranslational, nonenzymatic glycation of a variety of serum and structural proteins occur in normal and to a much greater extent in diabetic subjects. The glycation of serum albumin is of noteworthy clinical interest, since the extent of serum albumin glycation provides a useful means for accurately assessing the mean blood glucose level of diabetic subjects over short periods of time [l-3]. Therefore, it may be important to quantitate it accurately. Recently, Curtiss and Witztum [4] reported an elegant method for generating region-specific monoclonal antibodies to reductively glycated proteins, and quantifying glucitollysine residues on the total plasma proteins and isolated lipoproteins of normal and diabetic subjects after reduction of the proteins. In this report, we describe a radioimmunoassay (RIA) for glycated human serum protein using antiserum readily obtained by immunizing guinea pigs with reductively glycated human albumin. The antiserum was also capable of identifying and quantitating glucitollysine residues of human serum albumin after reduction of’ the protein with sodium borohydride (NaBH,).