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Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a randomized controlled trial.Setting & Participants: Participants in the CREDENCE trial.Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (Results: The mean age of the cohort was 63.0 ± 9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.

Aims/Introduction Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long‐term treatments are available. Methods This was an investigator‐initiated multicenter prospective intervention study in which ipragliflozin (50 mg) was administered once daily, and glycemic control, estimated glomerular filtration rate (eGFR) and adverse events were evaluated until 104 weeks after starting research. Results There were 407 patients analyzed. In the eGFR ≥90 group and eGFR ≥60 to 300 group and the eGFR, In the estimated glomerular filtration rate (eGFR) ≥90 group and eGFR ≥60 to

Background: Sodium/glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control and reduce body weight by increasing glycosuria. Although a compensatory increase of food intake has been repo...

Background: There are several reports of seasonal variation in hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2DM), but no reports of seasonal variation in the effect of add-on drugs on blood glucose control in insulin-treated patients. Methods: Using data collected from 630 patients in a multicenter study, we compared the amount of change in HbA1c after 1, 3, 6, 9, and 12 months of add-on administration of sitagliptin in insulin-treated patients divided into four groups based on the month when sitagliptin was started. Results: A significantly larger decrease in HbA1c at 6 months from baseline was observed in the group that started add-on sitagliptin in February to April than in the other three groups. However, the amount of change in HbA1c at 12 months did not differ among the groups. Conclusions: The consideration of seasonal variation enables more accurate evaluation of a drug’s short-term effect on blood glucose control. J Clin Med Res. 2020;12(3):200-208 doi: https://doi.org/10.14740/jocmr4103

Objective To examine the continuation of antibody prevalence and background factors in antibody-positive subjects after asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods A study was carried out to investigate the SARS-CoV-2 antibody (IgG) prevalence. SARS-CoV-2 antibodies (IgG) were measured and analyzed with immunochromatographic tests. Patients Among 1603 subjects, comprising patients, physicians, and nurses at 65 medical institutes in Kanagawa, Japan, 39 antibody-positive subjects received follow-up for 6 months. Results Of the 33 subjects who consented to the follow-up (23 patients and 10 medical professionals), continued positivity of IgG antibodies was confirmed in 11 of 32 cases (34.4%) after 2 months, 8 of 33 (24.2%) after 4 months, and 8 of 33 (24.2%) after 6 months. A significant difference was found in the sleeping time, drinking habits, hypertension, and use of angiotensin-receptor blockers on comparing subject background characteristics among three groups: patients with antibody production that continued for six months after the first detection of positivity, patients in whom antibody production stopped at four months, and patients in whom antibody production stopped at two months. Conclusions The continuation rate of IgG antibody prevalence was 24.2% at 6 months after the first detection of antibody positivity in cases with asymptomatic coronavirus disease 2019 (COVID-19) infections. This percentage is low compared with the antibody continuation rate in patients who have recovered from symptomatic COVID-19 infection.

Aim Long-term changes in body composition associated with SGLT2 inhibitors have not been characterized. Materials and methods In this multicenter, single-arm, open-label study, 107 subjects with type 2 diabetes were treated, as add-on therapy, with canagliflozin at 100 mg for 12 months. Body composition was measured with a body composition analyzer (T-SCAN PLUS) via the impedance method to prospectively analyze changes in body components, including percentage of body fat, body fat mass, total body water, muscle mass, and mineral mass. Estimated plasma volume (ePV) was calculated using the Kaplan formula. Results Body weight showed a significant decrease from 1 month to 12 months of treatment with canagliflozin, with a higher rate of decrease in body fat in body composition. A significant decrease in mineral mass was also observed, but its rate was low. Following treatment with canagliflozin, changes in total body water did not affect intracellular water, and a significant decrease in extracellular water, including plasma components, was observed early and sustained up to 12 months. Protein mass, a component of muscle mass, was not affected, with only a slight decrease in water volume observed. Conclusions Canagliflozin decreased extracellular fluid and plasma volume in addition to decreasing fat in the body due to calorie loss through urinary glucose excretion. This study suggested that SGLT2 inhibitors might reduce body weight by regulating fat mass or water distribution in the body and have cardiac and renal protective effects by resetting the homeostasis of fluid balance. This article is protected by copyright. All rights reserved.

Background: Sitagliptin, the first dipeptidyl peptidase-4 inhibitor, has demonstrated efficacy and safety as monotherapy and as add-on therapy to oral antidiabetic agents or insulin. However, there have been few reports about sitagliptin in elderly patients. The ASSIST-K observational study was performed in patients with type 2 diabetes mellitus (T2DM) receiving sitagliptin as add-on therapy to insulin. Changes of hemoglobin A1c (HbA1c), body weight, and the estimated glomerular filtration rate (eGFR), as well as adverse events, were investigated over 12 months in age-stratified groups. Methods: Among outpatients with T2DM treated at member institutions of Kanagawa Physicians Association, those starting sitagliptin as add-on therapy to insulin were followed for 12 months. HbA1c (National Glycohemoglobin Standardization Program), body weight, and eGFR were the efficacy endpoints, while adverse events were investigated to assess safety. Patients were stratified into three age groups (≤ 64 years, 65 - 74 years, and ≥ 75 years) for comparison of the endpoints. Results: Among 937 patients on insulin before starting sitagliptin, 821 patients were analyzed after excluding those without HbA1c data at baseline and 12 months. The two groups of elderly patients (65 - 74 years and ≥75 years) had more complications and their HbA1c was lower at initiation of sitagliptin therapy. The dose of sitagliptin, daily number of insulin injections, and number of concomitant oral antidiabetic agents were all lower in the elderly patients. HbA1c showed a significant decrease after initiation of sitagliptin in all age groups, and there were no significant intergroup differences in the change of HbA1c at 12 months. Body weight did not change significantly in any group. eGFR decreased significantly in all groups, with no significant intergroup differences at 12 months. Regarding adverse events, there were no significant intergroup differences in the incidence of severe hypoglycemia, gastrointestinal symptoms, or constipation. Conclusions: Despite baseline differences in demographic factors and medications, sitagliptin showed good efficacy and safety in all age groups of patients receiving it as add-on therapy to insulin during routine management of T2DM. Adding sitagliptin to insulin achieves similar efficacy and safety outcomes at 12 months in both elderly and non-elderly T2DM patients. J Clin Med Res. 2019;11(5):311-320 doi: https://doi.org/10.14740/jocmr3677

Background: Ipragliflozin is a selective sodium glucose co-transporter 2 inhibitor. The ASSIGN-K study is investigating the efficacy and safety of ipragliflozin for type 2 diabetes mellitus (T2DM) in the real-world clinical setting. Methods: Japanese T2DM patients with inadequate glycemic control despite diet and exercise with/without pharmacotherapy were enrolled in an investigator-driven, multicenter, prospective, observational study examining the efficacy and safety of ipragliflozin treatment (50 mg/day for 52 weeks). We performed interim analysis after 24 weeks. Results: In 367 patients completing 24-week ipragliflozin therapy, hemoglobin A1c (HbA1c) decreased significantly from 8.07% at baseline to 7.26% in week 24 (P < 0.001). The change in HbA1c from treatment initiation to week 24 was -0.88% in patients < 65 years old versus -0.55% in those ≥ 65 years and -0.92% in men versus -0.70% in women (all P < 0.001). When baseline HbA1c was < 7%, 7% to < 8%, and ≥ 8%, the change was -0.18%, -0.45%, and -1.48%, respectively (P = 0.5352, P < 0.001, and P < 0.001, respectively). When baseline body mass index (BMI) was < 25, 25 to < 30, and ≥ 30, the change was -1.05%, -0.65%, and -0.87%, respectively (all P < 0.001). Multiple regression analysis showed that HbA1c decreased more in patients with a higher baseline HbA1c or shorter duration of diabetes. An HbA1c < 7% was achieved in 33.3% of the patients, and their baseline HbA1c was significantly lower than that of patients failing to achieve it (P < 0.001). Adverse events (AEs) occurred in 106/451 patients (23.5%), including 29.1% of patients aged 65 or older. Common AEs were vulvovaginal candidiasis (3.1%) and genital pruritus (1.8%). Serious AEs included urinary tract infection, unstable angina, and ketosis, which occurred in patients who did not suspend medication during acute illness. Conclusions: Ipragliflozin significantly improved HbA1c in T2DM patients with inadequate glycemic control. Improvement in HbA1c was significant irrespective of age, sex, baseline HbA1c, or BMI, but efficacy was greater with a higher baseline HbA1c and shorter duration of diabetes. For safe continuation of treatment, patients should be advised to suspend medication during acute illness. J Clin Med Res. 2017;9(9):793-801 doi: https://doi.org/10.14740/jocmr3116w

Background: Ipragliflozin, a sodium-glucose transporter 2 inhibitor, was administered to patients with type 2 diabetes mellitus for 24 weeks to evaluate its effect on glycemic control and body composition. Methods: This was an investigator-initiated multicenter prospective intervention study in which ipragliflozin (50 mg) was administered once daily and glycemic control, blood pressure, body weight (BW), body composition (measured by a biological impedance method), the lipid profile, and adverse events were evaluated after 4, 12, and 24 weeks of treatment. Results: Efficacy and safety up to 24 weeks of ipragliflozin therapy were analyzed in 367 patients and 451 patients, respectively. Hemoglobin A1c decreased significantly from 8.07% at the start of ipragliflozin therapy to 7.26% in week 24 (P < 0.001). Fasting and postprandial blood glucose levels were significantly reduced by ipragliflozin. In week 24, there were significant decreases from baseline in BW (-2.6 kg), waist circumference (-2.9 cm), and body fat mass (-1.9 kg) (P < 0.001). The body water mass and mineral mass were decreased significantly by 0.5 and by 0.1 kg, respectively (P < 0.001), whereas the protein mass did not change significantly. Intracellular water mass did not change significantly, whereas extracellular water mass showed a significant decrease of 0.5 kg (P < 0.001). Muscle mass did not change in the upper and lower limbs, but that of the trunk decreased significantly (P < 0.001). There was a significant decrease in the fasting triglyceride level and a significant increase in fasting high-density lipoprotein cholesterol level, while low-density lipoprotein cholesterol was unchanged. Adverse events occurred in 23.5% of the patients, with a high frequency of genital infections, such as vulvovaginal candidiasis (3.1%) and genital pruritus (1.8%). Adverse drug reactions were noted in 13.7% of the patients. Conclusions: Administration of ipragliflozin for 24 weeks improved glycemic control and decreased BW. Reduction of body fat accounted for more than 70% of the total weight loss and reduction of extracellular water accounted for about 20%. J Clin Med Res. 2017;9(7):586-595 doi: https://doi.org/10.14740/jocmr3038w

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to reduce hemoglobin A1c (HbA1c) in patients with type 2 diabetes, but the reduction varies between patients and adequate glycemic control may not be achieved. We evaluated the efficacy and safety of the DPP-4 inhibitor alogliptin in the real clinical setting, and analyzed factors associated with the improvement of HbA1c by alogliptin treatment. Methods: A retrospective observational study was performed in patients with type 2 diabetes attending hospitals or clinics belonging to the Kanagawa Physicians Association who received treatment with alogliptin for 1 year or longer. Patients using insulin were excluded from the study. The efficacy endpoints were HbA1c (National Glycohemoglobin Standardization Program value), blood glucose (fasting/postprandial), body weight, blood pressure (systolic/diastolic), liver function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and γ-glutamyl transpeptidase), kidney function (serum creatinine and estimated glomerular filtration rate), serum lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), and serum amylase. Adverse events were compiled to assess safety. Results: Of 330 patients whose case records were collected, 27 patients were excluded for protocol violations, leaving 303 patients to form the full analysis set. Compared with baseline, HbA1c showed a decrease by 0.54±1.22% (mean ± standard deviation) after 12 months of alogliptin treatment. Factor analysis demonstrated that the change of HbA1c after 12 months was significantly influenced by the baseline HbA1c level, duration of diabetes, concomitant use of sulfonylureas, and compliance with diet therapy. In addition, there was a significant reduction of total cholesterol, low-density lipoprotein cholesterol, and the estimated glomerular filtration rate after 12 months of alogliptin treatment, as well as a significant increase in serum creatinine. No significant changes of body weight, blood pressure, or liver function were observed. Symptoms of hypoglycemia occurred in two patients (0.6%). Conclusions: Alogliptin displayed a significant hypoglycemic effect and excellent safety in routine clinical use. Factors influencing the change of HbA1c with alogliptin therapy may include the HbA1c at the start of treatment, the duration of diabetes, use of sulfonylureas, and compliance with diet therapy. J Clin Med Res. 2016;8(2):130-140 doi: http://dx.doi.org/10.14740/jocmr2418w

Background: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is an effective oral antidiabetic agent as both monotherapy and when combined with insulin. Data from three observational studies performed in patients with type 2 diabetes receiving sitagliptin therapy in the routine clinical setting were integrated to conduct factor analysis of the changes in hemoglobin A1c (HbA1c), body weight, and estimated glomerular filtration rate (eGFR) over 12 months. Methods: Among patients with type 2 diabetes attending medical institutions affiliated with Kanagawa Physicians Association, those using sitagliptin were followed for 1 year. In the ASSET-K and ASSIST-K studies, patients were managed by diabetologists, while they were managed by non-diabetologists in the ATTEST-K study. Patients were not administered insulin in ASSET-K, whereas insulin was administered in ASSIST-K. HbA1c (National Glycohemoglobin Standardization Program), blood glucose (fasting/postprandial), body weight, and renal function (serum creatinine and eGFR) were the efficacy endpoints. Factor analysis was performed by analysis of variance using the magnitude of the change in HbA1c, body weight, and eGFR after 12 months of sitagliptin therapy as response variables, and the study, sex, and age as explanatory variables. Results: Of 1,327 patients registered in ASSET-K (diabetologists/without insulin), 1,167 patients in ASSIST-K (diabetologists/with insulin), and 530 patients in ATTEST-K (non-diabetologists), statistical analysis was carried out on 1,074, 854, and 411 patients, respectively. There were significant inter-study differences in patient characteristics (complications, duration of diabetes, and baseline HbA1c), the sitagliptin dose, and the use of other antidiabetic agents. HbA1c decreased significantly in all three studies. According to factor analysis, the magnitude of the change in HbA1c over 12 months showed significant inter-study differences and was also significantly influenced by the age, duration of diabetes, and baseline HbA1c. Conclusions: Comparison of three observational studies identified differences in patient characteristics, treatment of diabetes (use/non-use of insulin), and the level of specialist care (diabetologist/non-diabetologist). Despite such differences, consistent reduction of HbA1c by sitagliptin was demonstrated in all three studies. The patients showing most improvement in HbA1c with sitagliptin therapy were older patients with a short duration of diabetes and high baseline HbA1c level. J Clin Med Res. 2016;8(6):461-471 doi: http://dx.doi.org/10.14740/jocmr2540w

Objectives Excessively short and long sleep durations are associated with type 2 diabetes, but there is limited information about the association between sleep quality and diabetes. Accordingly, the present study was performed to investigate this relationship. Materials and methods The subjects were 3249 patients with type 2 diabetes aged 20 years or older. Sleep quality was assessed by using the Pittsburgh Sleep Quality Index (PSQI). A higher global PSQI score indicates worse sleep quality, and a global PSQI score >5 differentiates poor sleepers from good sleepers. Results The mean global PSQI score was 5.94 ± 3.33, and 47.6% of the patients had a score of 6 or higher. Regarding the components of the PSQI, the score was highest for sleep duration, followed by subjective sleep quality and then sleep latency in decreasing order. When the patients were assigned to HbA1c quartiles (≤ 6.5%, 6.6–7.0%, 7.1–7.8%, and ≥ 7.9%), the top quartile had a significantly higher global PSQI score than the other quartiles. The top HbA1c quartile had a sleep duration of only 6.23 ± 1.42 hours, which was significantly shorter than in the other quartiles. Also, sleep latency was 25.3 ± 31.8 minutes in the top quartile, which was significantly longer (by approximately 20 minutes) than in the other quartiles. When analysis was performed with adjustment for age, gender, BMI, smoking, and other confounders, the global PSQI score was still significantly higher and sleep duration was shorter in the top HbA1c quartile (HbA1c ≥ 7.9%). Conclusions Japanese patients with type 2 diabetes were found to have poor subjective sleep quality independently of potential confounders, especially those with inadequate glycemic control. Impairment of sleep quality was associated with both increased sleep latency and a shorter duration of sleep.

Background: Ipragliflozin is a sodium-glucose co-transporter 2 inhibitor that can improve glycemic control and reduce body weight and blood pressure in patients with type 2 diabetes mellitus (T2DM). We evaluated the efficacy and safety of ipragliflozin in the real-world clinical setting, with a focus on the changes of body composition up to 3 months of treatment. Methods: This was a prospective multicenter interventional trial. We investigated changes of the blood pressure, body composition, blood glucose, hemoglobin A1c (HbA1c), ketone bodies, lipids, and insulin after treatment with ipragliflozin (50 - 100 mg/day) for 12 weeks in Japanese patients with T2DM who showed poor glycemic control despite receiving diet and exercise therapy with or without oral antidiabetic drugs for more than 12 weeks. Results: Two hundred and fifty-seven subjects were included in the efficacy analysis up to 12 weeks of treatment and 301 subjects were included in the safety analysis. From baseline to 12 weeks, HbA1c showed a change of -0.68% (95% confidence interval (CI): -0.83, -0.53) and fasting blood glucose showed a change of -23.9 mg/dL (95% CI: -30.5, -17.2), with both parameters displaying a significant reduction (P < 0.001). The difference of body weight from baseline was -1.82 kg (95% CI: -2.14, -1.50), and it also showed significant reduction (P < 0.001). Analysis of body composition revealed that body fat changed by -1.46 kg (95% CI: -1.79, -1.14, P < 0.001) and body water changed by -0.37 kg (95% CI: -0.60, -0.14, P < 0.01). Laboratory tests demonstrated improvement of liver function and the lipid profile. Adverse events (AEs) occurred in 22.6% of the subjects, with frequent events being vulvovaginal candidiasis in 2.7% and cystitis in 2.0%. Serious AEs occurred in three subjects. Conclusions: In patients with T2DM, ipragliflozin improved glycemic control after 1 month of treatment and caused weight loss by reducing body fat more than body water. J Clin Med Res. 2016;8(2):116-125 doi: http://dx.doi.org/10.14740/jocmr2417w Correction in J Clin Med Res. 2016;8(3):267-267, doi: http://dx.doi.org/10.14740/jocmr2417wc1

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

Background: It is unclear whether dipeptidyl peptidase-4 inhibitors decrease hemoglobin A 1c (HbA 1c ) in a glucose-dependent manner in patients on insulin therapy who have impaired insulin secretion. This study investigated factors influencing the efficacy of sitagliptin when used concomitantly with insulin to treat type 2 diabetes mellitus (T2DM) in the real-world setting. Methods: A retrospective study was conducted of 1,004 T2DM patients at 36 Japanese clinics associated with the Diabetes Task Force of the Kanagawa Physicians Association. Eligible patients had been on insulin for at least 6 months, with a baseline HbA 1c of 7.0% (53 mmol/mol) or higher. Baseline characteristics and laboratory data from 495 patients were subjected to multiple regression analysis to identify factors influencing the change of HbA 1c . Results: Most patients (n = 809) received sitagliptin at a dose of 50 mg. In the 1,004 patients, HbA 1c decreased by 0.74% (6 mmol/mol) and body weight increased by 0.1 kg after 6 months of combination therapy. Multiple regression analysis showed that a higher baseline HbA 1c , older age, and lower body mass index influenced the change of HbA 1c after 6 months. Hypoglycemic symptoms occurred in 7.4%, but none were severe. Conclusions: These results emphasize the importance of a higher HbA 1c at the commencement of sitagliptin therapy in patients on insulin. Glucose-dependent suppression of glucagon secretion by sitagliptin may be useful in patients with impaired insulin secretion. Sitagliptin can be used concomitantly with insulin irrespective of the insulin regimen, duration of insulin treatment, and concomitant medications. J Clin Med Res. 2015;7(8):607-612 doi: http://dx.doi.org/10.14740/jocmr2149w

Our goal was to evaluate liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in monotherapy and combination therapy for Japanese type 2 diabetes patients. Patients with type 2 diabetes (111 men, 83 women; mean age 57.6 ± 12.6 years) were treated with liraglutide and divided into liraglutide monotherapy (n = 147 patients, group A) and liraglutide–sulfonylurea (SU) combination therapy (n = 47, group B) groups. Changes in clinical parameters after liraglutide administration were evaluated. In both groups, significant decreases in glycosylated hemoglobin (HbA1c) were seen after 12 (group A, 7.01 ± 1.38 vs. 7.72 ± 1.57 %, p

Background: Ipragliflozin is a selective sodium glucose co-transporter 2 (SGLT2) inhibitor that blocks glucose reabsorption in the proximal tubules. SGLT2 inhibitors are expected to be effective in patients with insulin resistance and obesity, but it is important to select treatment according to patient background factors that minimizes the risk of adverse events. There have been a limited number of investigations into the relationship between the clinical efficacy (reducing hemoglobin A1c (HbA1c) and body weight (BW)) or safety of SGLT2 inhibitors and patient characteristics. Methods: ASSIGN-K is an investigator-initiated, multicenter, prospective observational study examining the efficacy and safety of ipragliflozin (50 - 100 mg/day for 52 weeks) in Japanese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with HbA1c ≥ 6.0% (National Glycohemoglobin Standardization Program) despite diet and exercise therapy or diet and exercise plus antidiabetic drug therapy. We conducted an interim analysis of the relationship between changes in HbA1c or BW and characteristics in patients who had been on treatment for more than 12 weeks. Results: In 257 patients completing 12 weeks of treatment, HbA1c decreased significantly from 8.23% to 7.55% (-0.68%, P < 0.01). The change in HbA1c after 12 weeks was -0.17%, -0.33%, and -1.16% when baseline HbA1c was < 7%, 7% to < 8%, and ≥ 8%, respectively (P < 0.05, P < 0.01, and P < 0.01, respectively), and -1.30%, -0.62%, and -0.62% when baseline body mass index (BMI) was < 25, 25 to < 30, and ≥ 30, respectively (all P < 0.01). Stratified analysis showed that age, gender, or BMI did not have a significant influence on the improvement in HbA1c. Multiple regression analysis showed that reduction in HbA1c was greater as baseline HbA1c increased and the duration of diabetes decreased. A higher baseline HbA1c was associated with less weight loss. Conclusions: Ipragliflozin significantly improved HbA1c in patients with T2DM. HbA1c improved more when baseline HbA1c was higher and the duration of diabetes was shorter, suggesting that current treatment policies for diabetes could be re-examined. J Clin Med Res. 2016;8(5):373-378 doi: http://dx.doi.org/10.14740/jocmr2492w

OBJECTIVE To investigate the relationship between fasting insulin levels and metabolic risk factors (MRFs) in type 2 diabetic patients at the first clinic/hospital visit in Japan over the years 2000 to 2009. RESEARCH DESIGN AND METHODS In total, 4,798 drug-naive Japanese patients with type 2 diabetes were registered on their first clinic/hospital visits. Conventional clinical factors and fasting insulin levels were observed at baseline within the Japan Diabetes Clinical Data Management (JDDM) study between consecutive 2-year groups. Multiple linear regression analysis was performed using a model in which the dependent variable was fasting insulin values using various clinical explanatory variables. RESULTS Fasting insulin levels were found to be decreasing from 2000 to 2009. Multiple linear regression analysis with the fasting insulin levels as the dependent variable showed that waist circumference (WC), BMI, mean blood pressure, triglycerides, and HDL cholesterol were significant, with WC and BMI as the main factors. ANCOVA after adjustment for age and fasting plasma glucose clearly shows the decreasing trend in fasting insulin levels and the increasing trend in BMI. CONCLUSIONS During the 10-year observation period, the decreasing trend in fasting insulin was related to the slight increase in WC/BMI in type 2 diabetes. Low pancreatic β-cell reserve on top of a lifestyle background might be dependent on an increase in MRFs.

(J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00221.x, 2012) Aims/Introduction: To determine the efficacy and safety of sitagliptin monotherapy and combination therapy in Japanese type 2 diabetes patients after 3 months’ therapy. Materials and Methods: A retrospective, observational study of 741 type 2 diabetes patients was carried out; 110 received sitagliptin monotherapy, and 631 received combination therapy with sitagliptin when other oral medications were insufficient. The primary outcome measure was glycated hemoglobin (HbA1c) measured at 0, 4 and 12 weeks of sitagliptin therapy. Results: In the monotherapy and combination therapy groups, HbA1c decreased significantly after 12 weeks. Target HbA1c (

Aims/Introduction: Insulin therapy is often required to achieve good glycemic control in patients with type 2 diabetes mellitus. However, some providers, particularly general practitioners (GPs), are reluctant to prescribe insulin to their patients. The aim of the present study was to clarify any differences in, as well as any problems associated with, insulin therapy in patients with type 2 diabetes being treated by either a GP or a diabetes specialist in Japan. Materials and Methods: Of 15,652 patients across 721 clinics and hospitals, 15,350 were diagnosed with type 2 diabetes (14,312 by GPs and 1038 by specialists). Data regarding glycated hemoglobin (HbA1c) levels, age, height, bodyweight and treatment modality were collected for each patient. Results: Of the patients with type 2 diabetes, 9.1 and 22.9% had been prescribed insulin monotherapy, and 38.8 and 37.0% were also receiving insulin with an oral antidiabetic (OAD) by GPs or specialists, respectively. Diabetes specialists prescribed analog insulin more frequently than did GPs. GPs chose premixed insulin more frequently than did specialists, and this factor correlated with higher HbA1c levels. A younger age and daily insulin dose in groups being treated by both providers were correlated with high HbA1c levels on insulin monotherapy. Neither type of insulin nor OAD was correlated with HbA1c on insulin plus OAD therapy. Conclusions: To achieve better glycemic control with insulin therapy, sufficient insulin dose and intensive treatment regimen, in addition to lifestyle interventions, might be necessary. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00198.x, 2012)

Aims/Introduction: The prevalence of diabetes mellitus is increasing rapidly in Japan, and diabetic neuropathy is a major factor decreasing diabetic patients’ quality of life, as well as a risk factor for sudden death. The present study aimed to determine the prevalence of diabetic neuropathy and raise awareness about it among patients and their physicians. Materials and Methods: Diabetic outpatients (N = 5077) at 249 medical institutions within Kanagawa Prefecture, Japan, were surveyed by questionnaire and underwent foot examinations. The questionnaire included 10 questions about sensory abnormalities of both feet, muscle cramps and autonomic symptoms. Foot examinations included testing for vibratory perception of the medial malleolus, Achilles tendon reflexes and touch sensation of the bottom of the great toe using tissue paper. Results: Of the 5077 patients surveyed, 70.4% reported symptoms. Overall, 75.4% of the patients underwent vibratory perception testing, of whom 44.9% had abnormal thresholds (≤10 s). On the tissue paper touch test, performed in 94.6% of patients, 11.9% had no touch sensation. Of the 2803 type 2 diabetic patients with known background factors who underwent foot examinations, 49.4% had diabetic neuropathy. There was a high prevalence of diabetic neuropathy (36.1%) in patients with

Sulfonylureas are commonly used for the treatment of patients with type 2 diabetes mellitus (T2DM). However, some clinical concerns regarding their use have grown over the past decade. Thus, results of a previous Japan-wide cross-sectional survey of patients with type 2 diabetes mellitus (T2DM) were analyzed to determine the present status and problems associated with the use of sulfonylureas in the treatment of T2DM by general practitioners (GPs) and diabetes specialists. Of 15,652 patients across 721 clinics and hospitals from the previous survey, 15,350 were diagnosed as T2DM (14,312 by GPs and 1,038 by specialists). For each patient, data were collected for HbA1c levels, age, height, body weight, and treatment modality. Of T2DM patients being treated by GPs, 35.4% and 60.0% received sulfonylureas in entire oral drugs or as monotherapy, respectively, compared with 29.2% and 61.2% of patients, respectively, treated by specialists. Of the patients treated with sulfonylurea monotherapy, 1335 patients (35.2%) achieved HbA1c

To determine the status of diabetes care by general practitioners and diabetes specialists in Japan, we conducted a nation-wide cross-sectional survey. We asked 8112 clinics and hospitals randomly, from throughout Japan, to participate in this study and 721 facilities agreed. A total of 15,652 patients aged from 15 to 97 with type 1 and type 2 diabetes were enrolled. Of these, 14,560 (93.0%) and 1092 (7.0%) patients were cared for by general practitioners and diabetes specialists, respectively. HbA1c levels were measured by a latex agglutination method, and age, height, body weight, type of diabetes and treatment modality were obtained from each patient. Mean HbA1c level for all patients treated by general practitioners was significantly lower than for those treated by the diabetes specialists (6.8±1.2% vs. 7.0±1.2%, p =0.0002). Mean HbA1c level for patients without insulin therapy was lower than for those treated with insulin, irrespective of caring physician. The proportion of patients treated with insulin therapy by diabetes specialists was higher (17.7%) than that by general practitioners (6.5%). This study showed that average HbA1c levels in Japanese patients treated by either general practitioners or specialists was acceptable, regardless of study limitations or bias.

Background There have only been a few reports about use of dipeptidyl peptidase 4 (DPP-4) inhibitors in elderly patients with type 2 diabetes mellitus (T2DM), suggesting that the safety of these agents has not been sufficiently demonstrated. We performed a comparative review of the efficacy and safety of sitagliptin for Japanese patients with T2DM managed in the real-world clinical setting. Methods An age-stratified analysis was performed of 831 patients who were treated with sitagliptin for 2 years. Parameters assessed included the hemoglobin A1c (HbA1c), body weight, serum creatinine, and adverse events. HbA1c and the incidence of hypoglycemia were also evaluated in patients treated with sitagliptin and a sulfonylurea (SU), who were divided into three age groups (

Aims/Introduction: Insulin therapy is often required to achieve good glycemic control in patients with type 2 diabetes mellitus. However, some providers, particularly general practitioners (GPs), are reluctant to prescribe insulin to their patients. The aim of the present study was to clarify any differences in, as well as any problems associated with, insulin therapy in patients with type 2 diabetes being treated by either a GP or a diabetes specialist in Japan. Materials and Methods: Of 15,652 patients across 721 clinics and hospitals, 15,350 were diagnosed with type 2 diabetes (14,312 by GPs and 1038 by specialists). Data regarding glycated hemoglobin (HbA1c) levels, age, height, bodyweight and treatment modality were collected for each patient. Results: Of the patients with type 2 diabetes, 9.1 and 22.9% had been prescribed insulin monotherapy, and 38.8 and 37.0% were also receiving insulin with an oral antidiabetic (OAD) by GPs or specialists, respectively. Diabetes specialists prescribed analog insulin more frequently than did GPs. GPs chose premixed insulin more frequently than did specialists, and this factor correlated with higher HbA1c levels. A younger age and daily insulin dose in groups being treated by both providers were correlated with high HbA1c levels on insulin monotherapy. Neither type of insulin nor OAD was correlated with HbA1c on insulin plus OAD therapy. Conclusions: To achieve better glycemic control with insulin therapy, sufficient insulin dose and intensive treatment regimen, in addition to lifestyle interventions, might be necessary. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00198.x, 2012)

Aims/Introduction: The prevalence of diabetes mellitus is increasing rapidly in Japan, and diabetic neuropathy is a major factor decreasing diabetic patients’ quality of life, as well as a risk factor for sudden death. The present study aimed to determine the prevalence of diabetic neuropathy and raise awareness about it among patients and their physicians. Materials and Methods: Diabetic outpatients (N = 5077) at 249 medical institutions within Kanagawa Prefecture, Japan, were surveyed by questionnaire and underwent foot examinations. The questionnaire included 10 questions about sensory abnormalities of both feet, muscle cramps and autonomic symptoms. Foot examinations included testing for vibratory perception of the medial malleolus, Achilles tendon reflexes and touch sensation of the bottom of the great toe using tissue paper. Results: Of the 5077 patients surveyed, 70.4% reported symptoms. Overall, 75.4% of the patients underwent vibratory perception testing, of whom 44.9% had abnormal thresholds (≤10 s). On the tissue paper touch test, performed in 94.6% of patients, 11.9% had no touch sensation. Of the 2803 type 2 diabetic patients with known background factors who underwent foot examinations, 49.4% had diabetic neuropathy. There was a high prevalence of diabetic neuropathy (36.1%) in patients with

Background : To evaluate the efficacy of switching from insulin to the GLP-1 receptor agonist liraglutide in type 2 diabetes mellitus patients. Methods : The subjects were 231 outpatients with type 2 diabetes mellitus being treated with liraglutide for the first time. For 161 patients, liraglutide was continued for 24 weeks (continuation group), and for 70 patients, liraglutide was discontinued before 24 weeks (discontinuation group). Fasting and postprandial blood glucose levels, HbA1c, body weight, and insulin dose were evaluated before the switch to liraglutide (baseline) and at 12 and 24 weeks of administration. Trends in HbA1c and weight were compared at 12 and 24 weeks of administration. Multiple regression analyses were conducted to identify clinical factors predicting a successful switch to liraglutide. Results : Multiple regression analysis with Δ HbA1c as the dependent variable in the continuation group indicated that HbA1c at 12 weeks of administration decreased with higher baseline HbA1c and increased with higher baseline daily insulin doses. Multiple regression analysis with Δ weight as the dependent variable indicated that Δ weight at 24 weeks of liraglutide administration was higher with higher baseline daily insulin doses and longer duration of diabetes. Based on the area under the receiver operating characteristic curve, cut-off values of 19 units for daily insulin dose and nine years for duration of diabetes were identified. Conclusions : Switching from insulin to liraglutide therapy is possible for carefully selected patients. Daily insulin dosage and duration of insulin therapy appear to be clinically useful indicators for the efficacy of liraglutide therapy. J Clin Med Res. 2014;6(2):138-144 doi: http://dx.doi.org/10.14740/jocmr1719w

Background: Sitagliptin is a DPP-4 inhibitor that became available for use in Japan three years ago. This study was conducted to identify the pleiotropic effects of sitagliptin other than blood glucose lowering in Japanese type 2 diabetes mellitus patients. Methods: A retrospective, observational study of 940 type 2 diabetes mellitus patients was conducted. The primary outcome measures were HbA1c, blood pressure, and lipid profiles measured at 0, 4, and 12 weeks of sitagliptin therapy. Results: After 12 weeks of sitagliptin treatment, compared with baseline, HbA1c decreased 0.64% ± 0.86% ; systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly ; and s erum creatinine (Cr) and uric acid (UA) levels were mildly but significantly elevated. A correlation analysis of the changes in systolic blood pressure, diastolic blood pressure, creatinine , and uric acid ( Δ SBP, Δ DBP, Δ Cr, Δ UA) from baseline to 12 weeks showed significant negative correlations between Δ SBP and Δ Cr, Δ SBP and Δ UA, and Δ DBP and Δ Cr. T otal cholesterol and p ostprandial tr i glycerides w ere significantly decreased at both 4 and 12 weeks . Alkaline phosphatase (ALP) decreased significantly, and there was a significant positive correlation between changes in ALP and HbA1c. Conclusions: S itagliptin seems to be effective not only in lowering blood glucose but also in lowering blood pressure , lipid , and ALP levels . S itagliptin appears to contribute to a Na-diuretic action due to GLP-1. d oi: http://dx.doi.org/10.4021/jocmr1061w