Type 2 Diabetes Mellitus In Japan Research Articles

Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data.

Diabetic retinopathy (DR), a microvascular complication of type 2 diabetes mellitus (T2DM), is a leading cause of blindness and has detrimental effects on patients' quality of life. We compared the risk of DR diagnosis with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with T2DM in Japan. This Japanese retrospective cohort study used the JMDC Claims Database (data collected from January 2015 to September 2022). Patients with T2DM and no record of microvascular or macrovascular diseases who were newly treated with an SGLT2i (23,061 patients) or a DPP-4i (53,986 patients) were matched 1:1 using propensity score (10,166 per matched group). Incidence rates (IRs) and cumulative IRs of DR diagnosis were calculated for each treatment group; hazard ratio (HR) and its 95% confidence interval (CI) were calculated using Cox proportional hazard models to compare the risk between the groups. The IR of DR diagnosis was 46.23 and 57.12 per 1000 person-years in the SGLT2i and DPP-4i groups, respectively, with a significantly lower risk in the SGLT2i group than in the DPP-4i group (HR 0.83, 95% CI 0.75-0.92, P = 0.0003). In this study, the risk of DR diagnosis was lower with SGLT2i compared with DPP-4i in patients with T2DM without microvascular and macrovascular diseases in Japan. Findings suggest that early SGLT2i treatment may be beneficial in preventing DR development in early-stage T2DM. Graphical abstract available for this article.

The combination of body mass index and fasting plasma glucose is associated with type 2 diabetes mellitus in Japan: a secondary retrospective analysis.

Body mass index (BMI) and fasting plasma glucose (FPG) are known risk factors for type 2 diabetes mellitus (T2DM), but data on the prospective association of the combination of BMI and FPG with T2DM are limited. This study sought to characterize the association of the combination of BMI and FPG (ByG) with T2DM. The current study used the NAGALA database. We categorized participants by tertiles of ByG. The association of ByG with T2DM was expressed with hazard ratios (HRs) with 95% confidence intervals (CIs) after adjustment for potential risk factors. During a median follow-up of 6.19 years in the normoglycemia cohort and 5.58 years in the prediabetes cohort, the incidence of T2DM was 0.75% and 7.79%, respectively. Following multivariable adjustments, there were stepwise increases in T2DM with increasing tertiles of ByG. After a similar multivariable adjustment, the risk of T2DM was 2.57 (95% CI 2.26 - 2.92), 1.97 (95% CI 1.53 - 2.54) and 1.50 (95% CI 1.30 - 1.74) for a per-SD change in ByG in all populations, the normoglycemia cohort and the prediabetes cohort, respectively. ByG was associated with an increased risk of T2DM in Japan. The result reinforced the importance of the combination of BMI and FPG in assessing T2DM risk.

Nutritional Risk Factors in Albuminuria and Retinopathy in Patients Newly Diagnosed With Type 2 Diabetes: A Cross-sectional Case Series Study.

Although nutritional risk factors for developing complications in type 2 diabetes mellitus (T2DM) have been examined, the effect of protein intake on nephropathy is debated, and there is little research on retinopathy. This cross-sectional case-series study aimed to examine the risk factors, including nutritional status, for complications in patients newly diagnosed with T2DM. Fifty-four patients were recruited, based on the results of examinations of blood glucose and/or glycated hemoglobin level for T2DM. To evaluate nutritional status, blood and urine examinations were performed and the Food Frequency Questionnaire was administered. Two-way analysis of variance, Fisher's exact test and logistic regression analyses were performed. The patients were categorized into four groups: 24 without albuminuria and without retinopathy, four without albuminuria with retinopathy, 21 with albuminuria without retinopathy, and five with albuminuria with retinopathy. Logistic analysis of albuminuria revealed that estimated sodium intake was significantly independent as the explanatory factors of age, sex, and body mass index. Patients with retinopathy had significantly higher blood urea nitrogen, and significantly lower plasma total protein levels than patients without retinopathy, suggesting that retinopathy is related to a higher catabolic state. Through a questionnaire on food intake, patients with retinopathy had a significantly lower intake of fat and monounsaturated fatty acids and a significantly higher intake of iodine based on intake of seaweed, corrected for energy intake, than patients without retinopathy. The present study may lead to planning a large cohort study for examining nutritional risk factors related to complications in patients newly diagnosed with T2DM in Japan.

Waist circumference glucose, a novel and effective predictor of type 2 diabetes: a prospective cohort study.

Waist circumference (WC) and fasting plasma glucose (FPG) have been demonstrated as risk factors for type 2 diabetes mellitus (T2DM). Evidence is limited regarding the association of the combination of WC and FPG (WyG) with the risk of T2DM. The primary aim of the study was to investigate the relationship between WyG and T2DM. The current study was a population-based cohort study using data from the NAGALA database. Participants were divided into tertiles based on WyG. Cox proportional hazard regression model was applied to identify the association of WyG with T2DM. During a median follow-up of 6.19 years in the normoglycemia group and 5.58 years in the prediabetes group, respectively, 88 and 285 individuals in the two groups received a diagnosis of T2DM. After full adjustment, risk of T2DM increased in step-wise fashion with increasing tertiles of WyG. For a per-SD increase in WyG, the hazard ratios for T2DM were 3.05 (95% CI 2.64 - 3.51) in all populations, 1.94 (95% CI 1.46 - 2.58) in the normoglycemia group and 1.63 (95% CI 1.40 - 1.90) in the prediabetes group. The interaction between WyG and fatty liver on T2DM was statistically significant in the prediabetes group (P for interaction = 0.034). Elevated WyG was independently associated with incident T2DM in Japan. Baseline WyG help identify individuals at high risk of T2DM and implement effective preventive measures.

1713-P: Dietary Manganese (Mn) Intake Is Independently Associated with a Lower BMI in Younger Japanese with Type 2 Diabetes Mellitus (T2DM)

We analyzed the association between dietary Mn intake and obesity measured by BMI after adjustment for intake of nutrients and food groups in people with T2DM in Japan. Participants were 1567 people, 63% male, aged 30 to 89 y who were in the Japan Diabetes Clinical Data Management Study Group (JDDM), one of the largest cohorts of Japanese with diabetes. Intake of food groups was determined by a validated self-administered food frequency questionnaire based on food groups. Obesity was defined as BMI ≥25 kg/m2. Multivariate logistic regression analysis assessed the relationship between quartiles of dietary Mn intake and obesity stratified by age. Participants aged 30 to 89 y were grouped according to the following quartiles for age: 30-54 y, 55-63 y, 64-71 y, and 72-89 y. Compared to the lowest quartile (Q1) for Mn, a significant negative association between Mn and BMI was found in males for all quartiles of Mn (OR [95%CI] of Q2= 0.643 [0.424 - 0.973], Q3= 0.607 [0.374 - 0.986], Q4= 0.398 [0.218 - 0.728], p trend = 0.028) with adjustment for characteristics such as age, sex, current smoking, drinking, insulin, oral hypoglycemic agents treatment, activity, energy intake and macronutrients intake. However, statistical significance disappeared after adding total fiber as a covariate. Compared to the lowest quartile for Mn, the highest quartile of Mn was inversely associated with BMI in the younger age group (30-54 y [OR= 0.296 [0.088 - 0.996]]) even after total fiber adjustment. Multivariate analysis of food groups (rice, vegetables, soy products) that were highly correlated with Mn as covariates showed that the relationships between Mn intake and obesity were maintained (p trend for rice, vegetables, soy = <0.001, 0.187, 0.010) in all participants. In summary, higher dietary Mn intake was independently associated with a lower BMI, especially in the younger group and males. Future prospective or intervention studies are expected to confirm this result. Disclosure L.Khin: None. H.Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kyowa Kirin Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd. Jddm study group: n/a. K.Fujihara: None. M.Hatta: None. Y.Takeda: None. S.Y.Morikawa: None. C.Horikawa: None. N.Kato: None. M.Kato: None. H.Maegawa: None.

Prescription Trends for the Antidiabetic Agents Used to Treat Type 2 Diabetes Mellitus in Japan from 2012-2020: a Time-Series Analysis.

In April 2014, sodium-glucose cotransporter 2 inhibitor (SGLT-2i) was introduced in Japan. In May 2015, the prescription limitation for SGLT-2i was lifted. Subsequently, SGLT-2i was shown to reduce cardiovascular events in patients with type 2 diabetes mellitus (T2DM). SGLT-2i prescription is expected to increase and consequently affect the prescription trends for other antidiabetic agents. Therefore, we evaluated the trends for antidiabetic agent prescriptions in Japan from April 2012 to March 2020. In this study, a dynamic cohort consisting of patients with T2DM derived from the Japan Medical Data Center health insurance database and with at least one antidiabetic agent prescription was investigated. The prescription rates were calculated monthly (/1000 person-months) for each class of antidiabetic agent. The eligible cohort comprised 34333 patients. The prescription rate for dipeptidyl peptidase-4 inhibitor increased from 424.0 in April 2012 to 656.3 in May 2015, and slightly decreased to 635.4 in March 2020. The prescription rate for biguanide consistently increased from 347.2 in April 2012 to 500.1 in March 2020. The prescription rate for sulfonylurea consistently decreased from 393.8 in April 2012 to 172.5 in March 2020. The prescription rate for SGLT-2i consistently increased from 4.1 in April 2014 to 363.1 in March 2020. SGLT-2i prescription increased and may affect the prescription trends for dipeptidyl peptidase-4 inhibitor and sulfonylurea after May 2015, when the prescription limitation for SGLT-2i was lifted. Biguanide prescriptions increased regardless of the introduction of SGLT-2i. The treatment of T2DM in Japan is clearly changing, with a focus on SGLT-2i and biguanide.

Combined association of oral and skeletal muscle health with type 2 diabetes mellitus among community-dwelling older adults in Japan: a cross-sectional study.

Objective: Although oral health and skeletal muscle status are known to be risk factors for type 2 diabetes mellitus (T2DM), there is limited information on their combined effects among community-dwelling older adults. The purpose of this study was to investigate the association between oral health and skeletal muscle status among older adults with T2DM in Japan.Participants and Methods: This cross-sectional study included data from individuals aged ≥60 years. T2DM was defined as a glycosylated hemoglobin A1c level ≥48 mmol/mol (≥6.5%) or the use of hypoglycemic agents. For oral health status, dental hygienists assessed the number of teeth (NT) and masticatory function (MF). Skeletal muscle status was assessed using skeletal muscle mass index (SMI) and handgrip strength (HGS). Logistic regression analysis examined T2DM in nine-category combinations of oral health status (each of the three categories in NT and MF) and skeletal status (each of the three categories in SMI and HGS).Results: T2DM was prevalent in 83 participants (16.4%) and was significantly associated with low NT and SMI (odds ratio [OR] = 5.93, 95% confidence interval [CI]: 1.37–25.73) and low MF and SMI (OR = 4.48, 95% CI: 1.23–16.35) compared to high NT and SMI and high MF and SMI, respectively.Conclusion: Our findings indicate that low muscle mass with tooth loss or masticatory dysfunction is associated with T2DM among community-dwelling older adults. This suggests that maintaining oral health and muscle mass may be an effective strategy for the prevention of T2DM.

Empagliflozin confers reno-protection in acute myocardial infarction and type 2 diabetes mellitus.

AimsAlthough the reno‐protective effects of sodium–glucose cotransporter 2 inhibitors are known in patients with heart failure or type 2 diabetes mellitus (T2DM), this effect has not been confirmed in patients with acute myocardial infarction (AMI).Methods and resultsThe prospective, multicentre, randomized, double‐blind, placebo‐controlled EMBODY trial investigated patients with AMI and T2DM in Japan. The eligible patients included adults aged 20 years or older, diagnosed with AMI and T2DM, and who could be discharged within 2–12 weeks after the onset of AMI. One hundred and five patients were randomized (1:1) to receive once daily 10 mg empagliflozin or placebo within 2 weeks of AMI onset. In this sub‐analysis, we investigated the time course of renal functional parameters such as serum creatinine levels and estimated glomerular filtration rate (eGFR) from baseline to Weeks 4, 12, and 24. Ninety‐six patients (64 ± 11 years, 78 male) were included in the full analysis (n = 46 and 50 in the empagliflozin and placebo groups, respectively). We used serum creatinine and eGFR as indicators of renal function. In the placebo group, eGFR decreased from 66.14 mL/min/1.73 m2 at baseline to 62.77 mL/min/1.73 m2 by Week 24 (P = 0.023) but remained unchanged in the empagliflozin group (from 64.60 to 64.36 mL/min/1.73 m2, P = 0.843). In the latter group, uric acid improved from 5.8 mg/dL at baseline to 4.9 mg/dL at Week 24 (P < 0.001). In the earlier analysis of 56 patients with eGFR ≥ 60 mL/min/1.73 m2, the eGFR decreased and the serum creatinine increased from baseline to 24 weeks in the placebo group, significantly different to the empagliflozin group (−6.61 vs. +0.22 mL/min/1.73 m2, P = 0.008 and +0.063 vs. −0.001 mg/dL, P = 0.030, respectively). The changes in serum creatinine and eGFR from baseline to Week 24 were significantly correlated with those in uric acid in the placebo group (r = 0.664, P < 0.001 and r = −0.675, P < 0.001, respectively) but not in the empagliflozin group.ConclusionsEmpagliflozin prevented the kidney functional decline in patients with AMI and T2DM, especially those with baseline eGFR ≥ 60 mL/min/1.73 m2. Early administration of sodium–glucose cotransporter 2 inhibitors in these patients is considered desirable for renal protection.

Determinants and impact of physical impairment in patient-reported outcomes among older patients with type 2 diabetes mellitus in Japan

Objective To investigate the predictive factors associated with physical impairment among older patients with type 2 diabetes mellitus (T2DM) in Japan and to examine the potential impact of physical impairment on patient-reported health outcomes in this population. Methods A cross-sectional analysis was conducted using patient-reported data from the 2012–2014 Japan National Health and Wellness Survey. Physical impairment was measured using the Physical Component Summary (PCS) score of the Short-Form 36-Item Health Survey (SF-36) three-component model (using Japanese norms). Older T2DM patients (≥65 years old; n = 1511) were dichotomized into physically impaired (PCS ≤ 25th percentile; n = 378) and non-physically impaired (PCS > 25th percentile; n = 1133). Work productivity (absenteeism, presenteeism and overall work impairment), activity impairment and healthcare resource utilization were compared between these groups. Results Age, female sex, low and high body mass index (BMI), diabetes-related complications, cardiovascular events, unawareness of having hypoglycemic events in the past 3 months, and lack of regular exercise were significant factors associated with physical impairment in multivariable analysis. The physically impaired group reported significantly more regular outpatient visits (13.48 vs. 10.16, respectively, p < .001), 1% or greater absenteeism (16.7% vs. 4.1%, p = .005), greater presenteeism (27.8% vs. 12.2%, p = .001), overall work impairment (30.0% vs. 13.0%, p = .001) and overall activity impairment (39.5% vs. 17.2%, p < .001) than the non-physically-impaired group after adjusting for covariates. Conclusions This study identified age, BMI, diabetes-related comorbidities, history of cardiovascular events and lack of exercise as key predictors associated with physical impairment in older patients with T2DM in Japan, which predicted low work productivity as well as activity impairment. This study provides support that physical impairment in patients with T2DM may lead to low work productivity and activity impairment. Supplemental data for this article is available online at https://doi.org/10.1080/03007995.2020.1846170.

Abstract 13363: Renoprotective Effects of Empagliflozin in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus; Subgroup Analysis of the Embody Trial

Introduction: Although renoprotective effect of sodium glucose co-transporter-2 (SGLT2) inhibitors has been recognized in the patients with heart failure or type 2 diabetes mellitus (T2DM), this protection has not been fully examined in patients with acute myocardial infarction (AMI). We therefore examined renoprotection of the SGLT2 inhibitor empagliflozin in patients with AMI and T2DM. Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT inhibitor on cardiac sympathetic hyperactivity in patients with AMI and T2DM in Japan. One hundred and five patients were randomized (1:1) to receive once-daily 10-mg empagliflozin, or placebo 2 weeks after the onset of AMI. In this sub-analysis, we specifically focused on the time-course of renal function on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients (64±11 y, 78 male) were included in the full analysis set (n = 46 and 50 in empagliflozin and placebo groups, respectively). In the placebo group, estimated glomerular filtration rate (eGFR) decreased from 66.1 at baseline to 62.8 mL/min/1.73m 2 on week 24, (P = 0.02). On the other hand, the empagliflozin group did not worsen it (from 64.6 to 64.4 mL/min/1.73m 2 , P = 0.84). The empagliflozin group exhibited the significant reduction in systolic blood pressure and uric acid level from baseline to week 24 (129.7 mmHg to 123.1 mmHg, P = 0.004, and 5.8 mg/dL to 4.9 mg/dL, P &lt; 0.0001, respectively), whereas the reduction was not significant in the placebo group (123.1 mmHg to 126.2 mmHg, P = 0.19, and 5.7 mg/dL to 5.8 mg/dL, P = 0.82, respectively). The change in eGFR from baseline to 24 weeks was negatively correlated with the changes in uric acid in the placebo group (r=0.685, P&lt;0.001), but not in the empagliflozin group. In stratified analysis among the patients with eGFR 60-90 mL/min/1.73m 2 , the empagliflozin group showed the significant increase in eGFR compared with the placebo group (+1.15 mL/min/1.73m 2 vs, - 6.43 mL/min/1.73m 2 , P=0.008), but not among the other population. Conclusions: Empagliflozin seemed to prevent the progression of renal dysfunction compared with placebo in the patients with AMI and T2DM. This tendency was remarkable when eGFR was 60-90 mL/min/1.73m 2 .

Quality-of-Life Comparison of Dapagliflozin Versus Dipeptidyl Peptidase4 Inhibitors in Patients with Type2 Diabetes Mellitus: A Randomized Controlled Trial (J-BOND Study).

IntroductionNo study has compared the effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP4is) on patients’ quality-of-life (QOL).MethodsWe enrolled 253 drug-naïve Japanese patients with type 2 diabetes mellitus (T2DM), randomly assigned them into a dapagliflozin (SGLT2i) group or DPP4i group in approximately 1:1 ratio, and monitored them for 24 weeks. The primary endpoint was the proportion of subjects indicating improvement in the “overall quality of life” domain of SHIELD-WQ-9 at week 24. Secondary endpoints included other domains of SHIELD-WQ-9, DTR-QOL, EQ-5D-5L, medication preference, medication adherence, diet therapy adherence, body weight, body mass index (BMI), abdominal circumference, HbA1c, and frequency of adverse events.ResultsThe proportion of subjects indicating improvement in the “overall quality of life” domain of SHIELD-WQ-9 at week 24 was higher in the dapagliflozin group (28.4%) than in the DPP4i group (18.6%) (p = 0.08). The proportion of subjects indicating improvement in the “physical health” domain of SHIELD-WQ-9 at week 24 was significantly higher in the dapagliflozin group (42.2%) than in the DPP4i group (23.7%) (p = 0.004). Total scores and domain 1 scores of DTR-QOL showed greater improvement in the dapagliflozin group (14.3 ± 15.6 and 15.5 ± 20.8, respectively) than in the DPP4i group (10.2 ± 15.6 and 10.3 ± 19.5, respectively) (both p = 0.05). EQ-5D-5L scores had significantly improved in the DPP4i group (0.023 ± 0.088) (p = 0.005); the intergroup difference was not significant (p = 0.14). Body weight (p < 0.001), BMI (p < 0.001), and abdominal circumference (p = 0.019) had significantly decreased in the dapagliflozin group compared with the corresponding values in the DPP4i group.ConclusionDapagliflozin showed a comparable or more favorable benefit on Japanese patients’ QOL compared with DPP4is. Dapagliflozin was well tolerated. It significantly reduced body weight, which was significantly correlated with improvement in the patients’ QOL. This study demonstrates that dapagliflozin can be used as a first-line drug for T2DM in Japan with a beneficial impact on patients’ QOL.Trial RegistrationUniversity Hospital Medical Information Network Clinical Trial Registry (UMIN000030514); Japan Registry of Clinical Trials (jRCTs051180165).Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-020-00941-8) contains supplementary material, which is available to authorized users.

Quality of Life and Utility Values for Cost-Effectiveness Modeling in Japanese Patients with Type2 Diabetes.

IntroductionReliable quality of life (QoL) measures and utility values are needed for patients with type 2 diabetes mellitus (T2DM) with a variety of comorbid conditions to help facilitate cost-effectiveness modeling. This study aimed to evaluate the Diabetes Treatment-Related Quality of Life (DTR-QOL) and EuroQol 5-dimension 5-level (EQ-5D-5L) questionnaires in patients with T2DM with and without diabetes complications and comorbidities in Japan.MethodsThis was an observational survey study involving 1000 patients with T2DM, at least 20 years old, receiving treatment at Nara University Hospital or Takamura Internal Medicine Clinic in Japan. Patients completed the DTR-QOL and EQ-5D-5L questionnaires and clinicians completed an accompanying case report form. The DTR-QOL and EQ-5D-5L are scored on a scale of 0–100 and 0–1, with 100 and 1 representing the best possible scores, respectively.ResultsOut of 1000 recruited patients, 978 were included in the final analysis. Patients reported an average EQ-5D-5L value of 0.92 ± 0.11. Utility values corresponded to the degree of severity of health conditions while few differences were observed when stratified by the HbA1c 7% threshold, age, or BMI level, nor did the values correspond to the degree of clinical risk factors. Patients reported an average total DTR-QOL score of 79.26 ± 13.26. The DTR-QOL was sensitive to detect differences in patients with T2DM with a variety of complications and comorbidities, risk factors, and treatments.ConclusionThis is the largest study to report QOL values for patients with diabetes in Japan and the first to include a variety of comorbid diabetic conditions. These findings may be useful for cost-effectiveness modeling of patients with T2DM in Japan.

Long-Term Safety and Efficacy of Sitagliptin for Type2 Diabetes Mellitus in Japan: Results of a Multicentre, Open-Label, Observational Post-Marketing Surveillance Study.

IntroductionA post-marketing surveillance (PMS) study was conducted to confirm the long-term risk–benefit profile of sitagliptin administered to Japanese patients with type 2 diabetes mellitus (T2DM) under real-world conditions.MethodsThis prospective, multicentre, open-label PMS collected data from 3326 patients receiving sitagliptin according to the approved indication during the case registration period (July 2010–June 2012; observation period, 3 years). Safety was assessed via collection of data on adverse drug reactions (ADRs), estimated glomerular filtration rate (eGFR) and cardiovascular events whereas efficacy was assessed via changes in glycated hemoglobin (HbA1c).ResultsIn 3265 patients evaluated for safety, 270 ADRs occurred in 207 (6.3%) patients overall. Metabolism and nutrition disorders were the most common class of ADRs, occurring in 58 patients overall (53 non-serious, 5 serious) with hypoglycaemia (17 patients, 0.52%) the most common ADR. In patients with eGFR > 90 mL/min/1.73 m2 at baseline (mean ± SD, 106.42 ± 18.11 mL/min/1.73 m2, n = 584), eGFR declined by 11.83 ± 17.53 mL/min/1.73 m2 (P < 0.0001; n = 360) over the observation period whereas eGFR appeared to be relatively maintained in patients with lower baseline eGFR levels. Cardiovascular events were infrequent [occurring in 4 of 84 (4.76%) patients at high cardiovascular risk] with no distinct features in this Japanese population and the cumulative incidence [8.42% (3.12–21.70) at 36 months; n = 32] was similar to that noted in previous studies involving sitagliptin. In patients evaluated for efficacy, the overall change in HbA1c from baseline to final evaluation was mean ± SD − 0.68 ± 1.34% (P < 0.0001, n = 2070). Reductions in HbA1c tended to be greater in younger patients and patients with higher body mass index (BMI) and HbA1c values at the start of administration.ConclusionLong-term sitagliptin administration in the routine clinical practice setting is associated with good efficacy, including as monotherapy, with no additional safety concerns.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01293-2) contains supplementary material, which is available to authorized users.

AD3 - Comparison of Persistence and Adherence Between Fixed-Dose Combination Therapy and Two-Pill Combination Therapy in Japanese Patients with Type 2 Diabetes Mellitus Using Two Administrative Databases

Real world evidence describing persistence and adherence of type 2 diabetes mellitus (T2DM) therapy focusing on combination drugs is limited in Japan. The aim of this study was to compare the treatment persistence and adherence of oral antidiabetic drugs (OADs) between fixed-dose combinations (FDC) and two-pill combination (TPC) therapy in adults with T2DM in Japan. Retrospective analyses of adults with T2DM initiating an OAD combination therapy between Jan. 1, 2011 and Dec. 31, 2015 were conducted using the Japan Medical Data Center (JMDC) and Medical Data Vision (MDV) databases. Patients initiating FDC therapy were matched (1:1) with those initiating TPC therapy (two OADs administered together) by propensity score to account for potential confounding factors. Persistence rates at 12 month were measured using the time from initiation until first discontinuation of the FDC or at least one of the drug class given concomitantly. Adjusted Cox proportional Hazard model (CPHM) was used to compare time to discontinuation between groups. Adherence was measured using the proportions of days covered (PDC) and non-adherence was defined as a PDC≤80%. After matching, 4,502 and 3,022 individuals were selected from JMDC and MDV, respectively (male: 78.0%/63.8%; mean age: 53.4/67.3). The major OAD combinations evaluated was dipeptidyl peptidase-4 inhibitor (DPP-4i) + thiazolidinedione (TZD) (64.1% [JMDC] and 70.5% [MDV]). Overall, persistent rates were higher in patients receiving FDC compared with TPC therapy (70.4% vs 66.2% [JMDC], 75.6% vs 55.7% [MDV]). In the JMDC population, persistent rates were highest with DPP-4i schedules (67.5–83.5%). Time to discontinuation was significantly longer with biguanide + TZD and DPP-4i + TZD FDC schedules (p<0.05) and adherence rates were ≥80% across all combinations in both databases. In this study, adults with T2DM treated with combination therapy were more persistent with FDC therapy than with TPC therapy given concomitantly.

The cost-effectiveness of dulaglutide versus insulin glargine for the treatment of type 2 diabetes mellitus in Japan

Aims: Dulaglutide is a new once weekly glucagon-like peptide-1 (GLP-1) receptor agonist administered via a disposable auto-injection pen for the management of type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the cost-effectiveness of dulaglutide vs insulin glargine for the management of T2DM from a Japanese healthcare perspective, in accordance with recently approved Japanese Cost-Effectiveness Guidelines.Methods: The IQVIA CORE Diabetes Model (version 9) was used to estimate the long-term costs and effects of treatment with dulaglutide and insulin glargine. Direct comparative data from the Araki 2015 trial (NCT01584232) was used to inform the analysis. Costs associated with treatment and complications were derived from Japanese sources wherever possible and inflated to 2015 Japanese Yen (JPY). Utilities were based upon a European systematic review of diabetes utilities and adjusted for use in a Japanese population. One-way and probabilistic sensitivity analyses (OWSA and PSA) were conducted on all inputs and key modeling assumptions.Results: Dulaglutide 0.75 mg was associated with higher quality-adjusted life years (QALYs), life years (LYs), and total costs, compared to insulin glargine, resulting in an incremental cost-effectiveness ratio (ICER) of 416,280 JPY/QALY gained. Treatment with dulaglutide increased the time alive and free from diabetes-related complications by 4 months. OWSA and PSA indicated that results were robust to plausible variations in input parameters and modeling assumptions.Limitations: Key limitations of this study are similar to other cost-utility analyses of diabetes, including the extrapolation of short-term clinical trial data into lifelong durations. In addition, due to the lack of robust published Japanese data, some values were derived from non-Japanese sources.Conclusions: This analysis suggests that dulaglutide 0.75 mg may be a cost-effective treatment alternative to insulin glargine for patients with T2DM in Japan.

Rationale and Design for the J-DISCOVER Study: DISCOVERing the Treatment Reality of Type 2 Diabetes in a Real-World Setting in Japan-A Protocol.

IntroductionIt is estimated that 642 million adults worldwide will have diabetes by 2040, with 80–90% of these having type 2 diabetes mellitus (T2DM). While many new antidiabetic agents have been introduced in recent years, approximately 40% of T2DM patients still fail to achieve the recommended target HbA1c of < 7.0%. Furthermore, many patients with T2DM in Japan are treated by practitioners other than diabetes specialists; therefore, the exact treatment patterns of T2DM in Japan are difficult to quantify.AimsJ-DISCOVER aims to address the lack of data on the management of T2DM by providing real-world data on disease management patterns and associated outcomes in a large number of Japanese T2DM patients who are initiating second-line therapy.Design and SettingPart of the global DISCOVER study program, J-DISCOVER will follow 2000 T2DM patients recruited from 141 sites across Japan who are aged ≥ 20 years. Recruitment began in September 2014 and follow-up will end in December 2018. The primary objective is to describe the long-term disease management patterns and clinical evolution of patients with T2DM inadequately controlled with a first-line antidiabetic therapy who initiate a second-line antidiabetic treatment. We will assess the associations between treatment patterns, including the line of antidiabetic medication used, as well as clinical and patient-reported outcomes. The primary endpoint is the mean change in HbA1c between baseline and at 6, 12, 24, and 36 months in the overall population and for patients receiving each class of second-line antidiabetic treatment.Planned OutputsA peer-reviewed publication reporting real-world results and implications for clinical practice.ConclusionBy enrolling and following a large number of patients with T2DM across Japan, J-DISCOVER is expected to provide important real-world clinical data for the development of future T2DM treatment guidelines.FundingAstraZeneca K.K. and Ono Pharmaceutical Co., Ltd., Osaka Japan.Clinical Trial RegistrationNCT02226822.Electronic supplementary materialThe online version of this article (10.1007/s13300-017-0351-7) contains supplementary material, which is available to authorized users.

Smoking and the risk of type 2 diabetes in Japan: A systematic review and meta-analysis.

Cigarette smoking is the leading avoidable cause of disease burden. Observational studies have suggested an association between smoking and risk of type 2 diabetes mellitus (T2DM). We conducted a meta-analysis of prospective observational studies to investigate the association of smoking status, smoking intensity, and smoking cessation with the risk of T2DM in Japan, where the prevalence of smoking has been decreasing but remains high. We systematically searched MEDLINE and the Ichushi database to December 2015 and identified 22 eligible articles, representing 343,573 subjects and 16,383 patients with T2DM. We estimated pooled relative risks (RRs) using a random-effects model and conducted subgroup analyses by participant and study characteristics. Compared with nonsmoking, the pooled RR of T2DM was 1.38 (95% confidence interval [CI], 1.28–1.49) for current smoking (19 studies) and 1.19 (95% CI, 1.09–1.31) for former smoking (15 studies). These associations persisted in all subgroup and sensitivity analyses. We found a linear dose-response relationship between cigarette consumption and T2DM risk; the risk of T2DM increased by 16% for each increment of 10 cigarettes smoked per day. The risk of T2DM remained high among those who quit during the preceding 5 years but decreased steadily with increasing duration of cessation, reaching a risk level comparable to that of never smokers after 10 years of smoking cessation. We estimated that 18.8% of T2DM cases in men and 5.4% of T2DM cases in women were attributable to smoking. The present findings suggest that cigarette smoking is associated with an increased risk of T2DM, so tobacco control programs to reduce smoking could have a substantial effect to decrease the burden of T2DM in Japan.

Basal Insulin Persistence, Associated Factors, and Outcomes After Treatment Initiation: A Retrospective Database Study Among People with Type 2 Diabetes Mellitus in Japan.

IntroductionThe objective of this study was to assess basal insulin persistence, associated factors, and economic outcomes for insulin-naïve people with type 2 diabetes mellitus (T2DM) in Japan.MethodsPeople aged at least 18 years with T2DM with first claim for basal insulin between May 2006 and April 2013 (index date), no insulin use before index date, and continuous insurance coverage for 6 months before (baseline) and 12 months after index date were selected from the Japan Medical Center Database. On the basis of whether there were at least 30-day gaps in basal insulin treatment, patients were classified as continuers (no gap), interrupters (at least one prescription after gap), and discontinuers (no prescription after gap). A multinomial logistic regression model identified factors associated with persistence. Annual healthcare resource use and costs in the year after initiation were compared between continuers and interrupters and between continuers and discontinuers using propensity score-based inverse probability weighting to adjust for baseline differences.ResultsOf the 827 people included (mean age 50 years, ca. 71% male), 36% continued, 42% interrupted, and 22% discontinued basal insulin therapy in the year after initiation. Having at least one inpatient visit and using fewer classes of non-insulin antihyperglycemic medications during baseline were associated with lower likelihoods of continuing therapy. Relative to interrupters and discontinuers, continuers had lower hospitalization rates [continuers, 12.7%; interrupters, 25.4% (p < 0.001); discontinuers, 28.4% (p < 0.001)] and lower inpatient costs [continuers, ¥132,013; interrupters, ¥225,745 (p = 0.054); discontinuers, ¥320,582 (p = 0.036)], but higher pharmacy costs [continuers, ¥158,403; interrupters, ¥134,301 (p = 0.039); discontinuers, ¥121,593 (p = 0.002)] in the year after insulin initiation. Total healthcare costs were similar for the three cohorts.ConclusionsSubstantial proportions of people with T2DM in Japan interrupt or discontinue basal insulin within the year after initiation, and they have higher rates and costs of hospitalizations than patients who continue with their insulin therapy. Further research is needed to understand reasons behind basal insulin persistence and the implications thereof to help clinicians manage T2DM more effectively.FundingEli Lilly and Company, Boehringer Ingelheim.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-016-0215-6) contains supplementary material, which is available to authorized users.

Patient Preference for Once-Weekly Dosing in Type 2 Diabetes Mellitus in Japan.

Background: Among several factors that impair adherence to available therapies in type 2 diabetes mellitus (T2DM) is the complexity of the dosing regimen. Moreover, the value of a once-weekly (QW) administration of oral medications for T2DM compared to once, twice, or thrice daily (QD, BID, TID) regimens is unclear. This study aims to identify subgroups and patient characteristics correlated with a preference for QW dosing compared to daily dosing using survey-based methods. Methods: This was a cross-sectional online survey study among patients with T2DM in Japan. Patients with T2DM were categorized into one of the three groups: (1) patients on treatment with oral hypoglycemic agent(s) only, (2) patients on combination treatment with oral hypoglycemic agent(s) and insulin, and (3) patients diagnosed with or suspected to have T2DM with no current or past experience with T2DM drug treatment (treatment naïve). Preliminary logistic regressions and classification and regression tree analysis (QW/QD dosing preferences as the dependent variable) were conducted to identify key predictors of dosing preference, followed by an evaluation of frequencies and trends in dosing preferences by the identified factors (subgroups). Results: Current treatment regimen, age, and work status were identified as the major demographic factors that were most predictive of QW preference. While, overall, 55.5% preferred QD and 33.3% preferred QW, the preference toward QW is higher in a specific cohort of patients that is treatment naïve (i.e., patients diagnosed with T2DM and/on diet/exercise therapy with no current or past experience with T2DM drug treatment) than who are on treatment, younger (age ≤64 years old), working full-time than part-time, and/or currently taking 0 or 1 drugs or more than 6 drugs (68.67% versus 30.12%). The most commonly cited reasons for QW preference were (1) "less burdensome because they didn't have to take it every day" (47.8%), (2) "less psychological burden" (14.6%), and (3) "forget to take it less often"(12.5%). Conclusion: Patients with T2DM vary in terms of preference for dosing regimens. Daily dosing was preferred over QW dosing in the overall population, however, preference for QW was higher in younger, full-time working, treatment naïve subjects, who are/or currently taking 0 or 1 drugs or more than 6 drugs.

Short duration of diabetes and disuse of sulfonylurea have any association with insulin cessation of the patients with type 2 diabetes in a clinical setting in Japan (JDDM 30)

Insulin therapy is often required to achieve good glycemic control for the patients with type 2 diabetes mellitus (T2DM), while protraction of glycemic control without insulin therapy may be preferable for patients. To determine the characteristics of and therapeutic regimen in outpatients with T2DM who were able to stop insulin therapy with satisfactory glycemic control in a real clinical practice setting in Japan by a case-control study. The present study was performed on 928 patients with T2DM who started insulin therapy in 2007. Data regarding age, sex, body mass index, duration of diabetes, HbA1c, postprandial plasma glucose, plasma fasting C-peptide immunoreactivity and treatment modality were compared between patients who were able to stop insulin therapy and those who continued with insulin. Of the 928 patients, 37 had stopped insulin therapy within 1 year. In the patients who stopped insulin therapy, the duration of diabetes was significantly shorter and the daily insulin dosage at initiation and the prevalence of sulfonylurea pretreatment significantly lower compared with patients who continued on insulin. In conclusion, almost 4% of T2DM patients were able to stop insulin therapy with satisfactory glycemic control in a real clinical practice setting in Japan. Shorter duration of diabetes and disuse of sulfonylureas prior to insulin may associate with stopping insulin therapy as a near-normoglycemic remission in outpatients with T2DM in Japan.