Glycemic Control In Japanese Patients Research Articles

The impact of handgrip strength and waist circumference on glycemic control: Prospective, observational study using outpatient clinical data in Japanese patients with type 2 diabetes mellitus.

Loss of muscle mass and the accumulation of visceral fat are known risk factors for the deterioration of glycemic control in type 2 diabetes mellitus. This study looked at the effects of such factors on glycemic control in Japanese patients with type 2 diabetes mellitus in the form of handgrip strength (HGS) and waist circumference (WC). In this prospective, observational study, 233 patients with type 2 diabetes mellitus and a HbA1c level of ≥7.0% were followed for around 1 year, during which time they were studied for an understanding of the association between handgrip strength, waist circumference, and glycemic control (HbA1c <7.0%). Hazard ratios (HRs) and 95% confidence intervals (CIs) for glycemic control improvement by Cox hazards models were analyzed for handgrip strength and waist circumference. Compared with the low tertile, patients in the middle and high tertiles of handgrip strength when adjustment was carried out for waist circumference were 2.117 (1.142-3.924) and 4.670 (2.526-8.632), respectively. The HRs of patients in the middle and high tertiles of WC when adjustment was made for HGS were 0.442 (0.269-0.725) and 0.339 (0.191-0.604), respectively. Within the low, middle, and high HGS tertiles, the HRs for WC were 0.863 (0.797-0.934), 0.940 (0.899-0.982), and 1.009 (0.984-1.035), respectively, although the HRs for HGS within each WC tertile remained significant. Handgrip strength and waist circumference demonstrated independent associations for glycemic control, but the effect of waist circumference appeared to be at least partially canceled out by increased handgrip strength. The data suggest that handgrip strength might help to mitigate the negative impact of waist circumference on glycemic control.

Prevalence of Metabolic Syndrome in Patients with Type2 Diabetes in Japan: A Retrospective Cross-Sectional Study.

Recent data on the prevalence of metabolic syndrome in Japanese patients with type2 diabetes (T2D) are limited. This retrospective, cross-sectional, observational study investigated the prevalence of metabolic syndrome in patients with T2D using a Japanese administrative claims database. Patients with a T2D diagnosis, prescription of a hypoglycemic agent, and one or more annual health checkups in 2020 were included. Trends in the prevalence of metabolic syndrome by sex and body mass index (BMI) subgroup were assessed. The study cohort consisted of 155,653 patients (men, 81.6%; mean age 54.6 ± 8.5years). Patients with metabolic syndrome had a higher mean BMI (29.1 ± 4.5kg/m2 versus 25.2 ± 4.5kg/m2) and mean waist circumference (98.3 ± 10.0cm versus 87.9 ± 11.2cm) compared to those without metabolic syndrome. Overall, the prevalence of metabolic syndrome was 43.0% in patients with T2D, with prevalence higher in men (46.6%) than women (27.0%). The prevalence increased across BMI subgroups from 17.3% in the < 25kg/m2 subgroup, to 54.6% and 66.1% in the 25 to < 30 and ≥ 30kg/m2 subgroups, respectively. A greater proportion of patients with metabolic syndrome had cardiovascular or renal comorbidities (BMI < 25, 0.3-2.0%; BMI 25 to < 30, 0.7-6.2%; BMI ≥ 30kg/m2, 0.7-6.8%) and cardiovascular drug usage (BMI < 25, 1.3-9.0%; BMI 25 to < 30, 3.8-31.1%; BMI ≥ 30kg/m2, 3.5-37.0%) in the higher BMI subgroups compared to the BMI < 25kg/m2 subgroup. The prevalence of metabolic syndrome in Japanese patients with T2D was 43.0% and increased with higher BMI. In patients with T2D and metabolic syndrome, cardiovascular drug usage and comorbidities increased in patients with a higher BMI. These data highlight the importance of managing metabolic parameters in addition to glycemic control in Japanese patients with T2D, particularly in patients with metabolic syndrome and BMI ≥ 25kg/m2.

Efficacy of treatment with glucagon-like peptide receptor agonists-1 in Asian patients with type 2 diabetes mellitus

The projected 68% increase in patients with type 2 diabetes mellitus (T2D) in the upcoming decades and the specific pathophysiological course of the disease are critical factors for the development of optimal disease management tactics in the Asian population. It is now known that β-cell dysfunction is dominant in the pathogenesis of T2D in Asians. In a number of Asian countries, incretin therapy is the leading therapy. To review literature on glucagon-like peptide-1 (GLP-1) secretion and clinical trial results of GLP-1 receptor agonist class (GLP-1RA) drugs as well as to evaluate their effectiveness in Asian population with T2D. A review of studies on pathophysiological aspects of GLP-1 secretion and evaluation of the efficacy of therapy with GLP-1RA preparations registered and used in clinical practice in Asian regions. Several studies in Asian countries have shown that intact GLP-1 levels were significantly lower in both T2D patients and healthy Japanese volunteers; as well as in patients with impaired glucose tolerance. It is suggested that either impaired secretion of GLP-1 in the gut, accelerated processing by dipeptidyl peptidase-4, or a combination of both are responsible for the decrease in GLP-1. The greater efficacy of GLP-1RA treatment in achieving glycemic control in Asian T2D patients was presented by Kim Y.G. et al. in a meta-analysis of 15 randomised controlled trials, the reduction in HbA1c on GLP-1RA treatment averaged -1.16% in Asian-dominated studies and -0.83% in non-Asian-dominated studies. In the PIONEER 9 clinical programme, similar results were obtained, with oral semaglutide having a more pronounced effect on glycaemic control in Japanese patients. Thus, the mean change in HbA 1c was -1.1%, 7 mg -1.5%, and 14 mg -1.7% at the 3 mg dose; whereas in the PIONEER 1 study in the global population, the mean change in HbA1c was -0.6%, -0.9% and -1.1% for 3, 7, 14 mg semaglutide, respectively. The PIONEER 10 study concluded that oral semaglutide was well tolerated by Japanese patients with T2D. Oral semaglutide reduced HbA1c (14 mg dose) and body weight (7 and 14 mg doses) more significantly compared to dulaglutide at 0.75 mg dose. Results of a pooled analysis of long-acting GLP-1RA showed a more significant reduction in cardiovascular event risk in the Asian subpopulation. The presented review describes benefits in glycemic control as well as in the reduction of relative cardiovascular event risks with GLP-1RA treatment in the Asian population, which requires further in-depth research and implies optimal management tactics in patients with T2DM.

Effects of Sacubitril/Valsartan on Glycemic Control in Japanese Patients With Heart Failure and/or Hypertension.

Background: Post hoc analysis of the PARADIGM-HF trial showed that sacubitril/valsartan (S/V) was more effective than enalapril in lowering HbA1c in patients with heart failure and diabetes. Methods and Results: In the present study, the effect of S/V on glycemic control was retrospectively analyzed in 150 patients (median age 74 years) who were prescribed S/V for the treatment of heart failure and/or hypertension. After a median period of 13 weeks treatment, mean (±SD) HbA1c levels decreased significantly from 6.56±0.68% to 6.49±0.63%. The decrease in HbA1c was evident in patients with (n=111), but not in those without, diabetes. There were no significant changes in renal function after S/V treatment, but systolic blood pressure was significantly reduced from 141±21 to 134±19 mmHg. Ninety patients had N-terminal pro B-type natriuretic peptide (NT-proBNP) tested, and S/V significantly decreased median NT-proBNP concentrations from 1,026 to 618 pg/mL; however, there was no correlation between the degree of decrease in HbA1c and that in NT-proBNP. Multiple regression analysis revealed that being diabetic, rather than having heart failure, was a significant independent variable for a reduction in HbA1c. Conclusions: Treatment with S/V improved glycemic control in patients with heart failure and/or hypertension, especially in those with concomitant diabetes. This favorable effect on glucose metabolism may be mediated by neprilysin inhibition and is desirable in the treatment of heart failure and hypertension in diabetic patients.

Impact of gender differences on lifestyle and glycemic control in Japanese patients with diabetes during COVID-19 lockdowns

AimsThe COVID-19 pandemic has drastically changed global lifestyles. Some reports about lifestyle changes during this pandemic have been published. However, these studies have not assessed gender differences. Thus, we analyzed three lifestyle changes to determine gender differences. MethodsWe analyzed physical activity, snacking habits, and drinking habits in 323 patients with diabetes. Gender differences in lifestyle habits were analyzed using the ꭓ2 test, and comparisons of HbA1c between 2019 and 2020 were analyzed using the paired t-test. The factors that influenced the deterioration of HbA1c were determined using multivariate logistic regression analyses. ResultsOf the 323 patients, 212 were male and 111 were female. When examined by quarter, the HbA1c values increased significantly in 2020 compared with that in 2019 in the July–September period. In terms of gender differences in the changes of lifestyle habits, decreased physical activity was higher in women. The factors that affected deterioration in HbA1c were snacking habits for the overall and the male populations. ConclusionsThe lifestyle changes differed between the genders during the pandemic. A balanced diet is important for all patients with diabetes. Additionally, more attention should be paid to physical inactivity in women.

Effects of barley intake on glycemic control in Japanese patients with type 2 diabetes mellitus undergoing antidiabetic therapy: a prospective study.

Barley reportedly reduces postprandial hyperglycemia in healthy individuals. However, its effects in patients with type 2 diabetes mellitus (T2DM) undergoing antidiabetic therapy remains unclear. This study aimed to clarify the effects of barley intake on postprandial hyperglycemia in T2DM patients who use metformin or acarbose. T2DM patients who were undergoing dietary therapy without medications (naive), with metformin, or with acarbose (n = 10/group) were recruited. They were instructed to eat white rice twice per day for 5 days, followed by barley-mixed rice twice per day for 6 or 7 days. Subsequently, blood glucose fluctuations in the interstitial fluid glucose were measured using a continuous glucose monitoring device. Meal tolerance tests were performed using test diets containing white rice and barley-mixed rice before and after the trial, respectively. Postprandial hyperglycemia was lower in patients taking barley-mixed rice than in those taking white rice in each group. However, the AUC of blood glucose concentration in the acarbose-treated patients showed only a trend. Mean amplitude of glycemic excursions (MAGEs) decreased in patients who consumed barley-mixed rice. Additionally, although MAGEs in the naive decreased, it did not in the metformin- (P = 0.098) and acarbose-treated (P = 0.29) patients. Barley-mixed rice lowers postprandial glucose concentrations in treatment-naive and metformin-treated T2DM patients, and shows a trend in acarbose-treated patients. Therefore, using barley-containing diets as dietary therapy may be useful in improving glycemic control in diabetes patients. UMIN000028623. The online version contains supplementary material available at 10.1007/s13340-021-00552-z.

Combination Therapy of Alpha-Glucosidase Inhibitor, Thiazolidinedione and Sodium Glucose Co-Transporter-2 Inhibitor in Japanese Type 2 Diabetes Patients

Background: We additionally administered selective inhibitor of sodium glucose co-transporter-2 (SGLT2) inhibitor to type 2 diabetic patients on alpha-glucosidase inhibitor (alpha-GI) and/or thiazolidinedione (TZD), to determine whether the multi-drug combination therapy including SGLT2 inhibitor further improved the glycemic control in Japanese patients with diabetes mellitus. Methods: The subjects were divided into four groups. Group I was administered an SGLT2 inhibitor in addition to ongoing treatment using hypoglycemic agents other than alpha-GI and SGLT2 inhibitor. Group II was administered an SGLT2 inhibitor in addition to an alpha-GI. Group III was administered an SGLT2 inhibitor in addition to a TZD. Group IV was administered an SGLT2 inhibitor in addition to an alpha-GI and TZD. The body weight and biochemical parameters were measured before and 1, 2 and 3 years after the start of SGLT2 inhibitor treatment. Results: In patients receiving alpha-GI or TZD, additional administration of an SGLT2 inhibitor resulted in a reduction of the body weight, body mass index (BMI) and serum uric acid level, but had little effect on the glucose or lipid metabolism. On the other hand, additional administration of SGLT2 inhibitor in patients receiving both alpha-GI and TZD (three-drug combination therapy) resulted not only in a reduction of the body weight, BMI and serum uric acid, but also in improvement of the glucose and lipid metabolism, with a reduction of the hemoglobin A1c level and increase of the serum high-density lipoprotein cholesterol level. Conclusion: The results suggest that three-drug combination therapy with alpha-GI, TZD and SGLT2 inhibitor, each of which has different mechanism of action, is beneficial for the treatment of type 2 diabetes mellitus. J Endocrinol Metab. 2020;10(6):167-172 doi: https://doi.org/10.14740/jem708

Efficacy and safety of insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi) in Japanese patients with type 2 diabetes mellitus inadequately controlled on basal insulin and oral antidiabetic drugs: The LixiLan JP-L randomized clinical trial.

To assess efficacy and safety of fixed-ratio (1:1) combination insulin glargine and lixisenatide (iGlarLixi) compared to insulin glargine U100 (iGlar), with metformin, in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on basal insulin and oral antidiabetic drugs (OADs). This 26-week, randomized, open-label study compared iGlarLixi to iGlar, both with metformin in adult Japanese patients with T2DM and hemoglobin (Hb) A1c ≥7.5% to ≤9.5%, treated with basal insulin and 1 or 2 OADs. Five hundred and twelve patients were randomized after a 12-week run-in, when iGlar was introduced and/or further titrated and OADs other than metformin were stopped. The primary endpoint was change in HbA1c from baseline to week 26. iGlarLixi (n = 255) demonstrated significantly greater reductions in HbA1c (-1.27%) than iGlar (n = 257, -0.53%) (LS mean difference: -0.74%, P < .0001) at week 26, confirming the superiority of iGlarLixi. Significantly, more iGlarLixi patients reached target HbA1c <7% at week 26 (51.8% vs 16.0% for iGlar). iGlarLixi patients lost weight in contrast to iGlar patients (-0.51 kg vs +0.55 kg). Documented symptomatic hypoglycemia (plasma glucose ≤ 3.9 mmol/L) was observed in 18.8% of iGlarLixi patients vs 16.7% of iGlar patients. iGlarLixi patients had more gastrointestinal-related adverse events than iGlar patients (33.3% vs 8.6%), primarily nausea (16.9% vs 0.8%). However, the treatment was generally well-tolerated. A once-daily injection of iGlarLixi with metformin is an effective, well-tolerated, and simple therapeutic intervention providing significant improvement in glycemic control in Japanese patients with T2DM inadequately controlled on basal insulin and up to two OADs. Clinical Trial Number: NCT02752412.

Ultra-Rapid Lispro Efficacy and Safety Compared to Humalog® in Japanese Patients with Type1 Diabetes: PRONTO-T1D Subpopulation Analysis.

IntroductionWe evaluated the efficacy and safety of ultra-rapid lispro (URLi) in comparison to lispro in a subgroup analysis of Japanese adults with type 1 diabetes mellitus from the phase 3 PRONTO-T1D trial.MethodsAfter an 8-week lead-in to optimize basal insulin treatment, patients were randomized to 52-week double-blind mealtime URLi or lispro, or 26-week open-label postmeal URLi. The primary endpoint was change in hemoglobin A1c (HbA1c) from baseline (week 0) to week 26 between mealtime URLi and lispro. The multiplicity adjusted objectives were 1- and 2-h postprandial glucose (PPG) excursions after a meal test between mealtime URLi and lispro, and change in HbA1c from baseline to week 26 between postmeal URLi and mealtime lispro.ResultsThis manuscript presents pre-specified exploratory analyses of 26-week data from Japanese patients randomized to double-blind URLi (n = 62) or lispro (n = 59), or open-label URLi (n = 46). Mean baseline HbA1c levels were 7.52% for mealtime URLi, 7.44% for lispro, and 7.51% for postmeal URLi at randomization. At week 26, the least squares mean (LSM) difference compared to lispro was 0.04% (95% confidence interval [CI] − 0.14 to 0.22) for mealtime URLi, and 0.16% (95% CI − 0.04 to 0.35) for postmeal URLi. In comparison to lispro, mealtime URLi resulted in statistically significantly lower 1- and 2-h PPG excursions during the mixed-meal tolerance test. LSM differences were − 40.5 mg/dL, 95% CI − 59.5 to 21.4 (− 2.25 mmol/L, 95% CI − 3.3 to − 1.2) for 1-h PPG excursions and − 51.7 mg/dL, 95% CI − 81.7 to − 21.8 (− 2.87 mmol/L, 95% CI − 4.5 to − 1.2) for 2-h PPG excursions at week 26. There were no significant treatment differences in rates of severe/overall hypoglycemia, or incidence of treatment-emergent adverse events.ConclusionsMealtime and postmeal URLi provide effective and comparable glycemic control in Japanese patients. Mealtime URLi demonstrated more effective PPG control compared to lispro.Trial RegistrationClinicalTrials.gov, NCT03214367.

1993-P: Impact of Laparoscopic Sleeve Gastrectomy on Glycemic Control in Japanese Patients with Obesity and Type 2 Diabetes

Background and Aims: Metabolic surgery has been proven to be effective for improving long-term outcome in patients with obesity and T2DM in Western countries. We aimed to evaluate the effects of this treatment in Japanese patients. Methods: We enrolled Japanese patients with obesity and T2DM who underwent laparoscopic sleeve gastrectomy (LSG) in our hospital from October 2016 to November 2019. We compared changes in body weight, HbA1c, antidiabetic drugs, and various metabolic parameters from preoperative baseline and 6 months after LSG. Results: Fifty-one patients with obesity underwent LSG; 26 had T2DM (age, 46.2±9.2 years; duration of diabetes, 9.5±7.4 years; female sex, 65.0%). Patients’ body weight, BMI and HbA1c decreased significantly (108.1±16.7 to 88.4±15.7 kg, 39.9±5.8 to 32.7±5.9 kg/m2 and 7.4±1.2 to 6.0±0.8%, respectively). The number of antidiabetic drugs significantly decreased postoperatively (2.1±1.2 to 0.6±1.0). Among them, 18 patients completely discontinued antidiabetic drugs. And all of five patients on insulin preoperatively maintained good glycemic control without insulin injections after LSG. The T2DM remission rate (HbA1c &amp;lt; 6.5% and no antidiabetic medications for 6 months) was 76.9%. ROC curve analysis revealed that the remission rates were low in patients with preoperative mABCD score ≤ 5 and DiaRem score ≥ 6. Dyslipidemia, hypertension and liver enzyme elevation improved significantly after LSG as well. There were no serious complications related to LSG; one patient experienced suture failure. Conclusion: LSG for Japanese patients with obesity and T2DM improved both body weight and glycemic control, as well as other various metabolic-related diseases. Six months after LSG, the T2DM remission rate was comparable in Japanese patients to Westerns. In addition, LSG significantly reduced the amount of antidiabetic drugs, suggesting that LSG has some advantage in healthcare costs. Disclosure Y. Oe: None. T. Takase: None. K. Cho: None. A. Nakamura: None. H. Nomoto: None. H. Kameda: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd.

A Real-World Observational Study Evaluating the Probability of Glycemic Control with Basal Insulin or Glucagon-Like Peptide-1 Receptor Agonist in Japanese Patients with Type 2 Diabetes.

IntroductionThe effectiveness of basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in providing glycemic control in patients with type 2 diabetes (T2D) in Japanese routine practice is not well known. This real-world observational study evaluated the probability of achieving glycemic control in Japanese patients with T2D uncontrolled by oral antidiabetic drugs (OADs) who initiated BI or GLP-1 RA therapy.MethodsPatients with T2D aged ≥ 18 years initiating BI or GLP-1 RA therapy following treatment with OADs were selected from real-world data (RWD) retrieved from a large electronic medical record database in Japan, using data from 01 January 2010 to 30 June 2019. Patients were required to have glycated hemoglobin (HbA1c) ≥ 7% within 90 days prior to the first prescription of BI or GLP-1 RA. The probability of reaching first HbA1c < 7% was assessed over a 24-month period in cohorts of patients who initiated BI (n = 3477) or GLP-1 RA (n = 780) and in subcohorts by number of OADs at baseline (1, 2, or ≥ 3), HbA1c at baseline (≥ 7 to < 8%, ≥ 8 to < 9%, or ≥ 9%), and age (< 65 or ≥ 65 years).ResultsMean (standard deviation) baseline HbA1c was 9.4% (1.8%) and 8.8% (1.4%) in patients initiating BI or GLP-1 RA therapy, respectively. The cumulative probability of achieving glycemic control was 50.1% with BI and 60.3% with GLP-1 RA therapy, respectively, at 12 months, and 60.8% and 66.6%, respectively, at 24 months. Quarterly (3-month intervals) conditional probabilities of achieving glycemic control decreased over time and were < 10% after 12 months. Patients with more OADs or higher HbA1c at baseline had a lower probability of achieving glycemic control.ConclusionAmong Japanese patients with T2D who initiated BI or GLP-1 RA therapy after treatment with OADs, the probability of reaching first glycemic control diminished over time. Further therapy intensification is warranted in patients who do not achieve glycemic control within 6–12 months with BI or GLP-1 RA, particularly those with high HbA1c or taking multiple OADs.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00836-8) contains supplementary material, which is available to authorized users.

IDegLira Improves Glycemic Control in Japanese Patients with Uncontrolled Type 2 Diabetes on Premixed Insulin Therapy.

IntroductionDUAL II Japan (NCT02911948) was a 26-week, phase 3a randomized, treat-to-target trial which compared the efficacy and safety of IDegLira with degludec in 210 Japanese patients with type 2 diabetes (T2D) uncontrolled on premixed or basal insulin therapy. The DUAL II Japan trial presented the opportunity for a post hoc analysis to examine the safety and efficacy of switching patients from a premixed regimen (containing both basal and bolus insulin components) to IDegLira.MethodsPatients from DUAL II Japan were stratified according to prior insulin regimen (premixed or basal insulin). The following endpoints were assessed in this post hoc analysis by pre-trial insulin regimen: change in HbA1c, body weight, daily total insulin dose, nine-point self-measured blood glucose, and severe or blood glucose-confirmed hypoglycemia (defined as severe or plasma glucose less than 56 mg/dL).ResultsThis post hoc analysis included 39 patients who switched from premixed insulin to IDegLira. The treatment effect in this population was independent of insulin type at baseline (premixed or basal; interaction test, P = 0.2535). In patients switching from premixed insulin to IDegLira, mean [standard deviation (SD)] HbA1c was 8.26% (0.73) at baseline and 6.68% (0.93) at week 26. Mean (SD) body weight was reduced by 1.5 (2.9) kg. At week 26, daily insulin dose was 34.2 dose steps. After 26 weeks, the mean prandial increment was smaller at all meals with IDegLira irrespective of pre-trial insulin regimen. Rate of hypoglycemic events was 2.59 events/patient-year of exposure over the 26 weeks.ConclusionThis post hoc study is the first to evaluate the switch from premixed insulin to IDegLira in patients with uncontrolled T2D. IDegLira initiation resulted in improved HbA1c and weight loss. This study offers insight into the effectiveness and safety of switching patients from premixed insulin therapy to IDegLira, and provides support for further investigation.Trial RegistrationNCT02911948.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-00730-y) contains supplementary material, which is available to authorized users.

Influence of Timing of Insulin Initiation on Long-term Glycemic Control in Japanese Patients with Type 2 Diabetes: A Retrospective Cohort Study.

Objective Delays in insulin initiation can lead to the development of complications in the management of type 2 diabetes. Methods In this study, the effects of the timing of insulin initiation on glycemic control in patients with type 2 diabetes were evaluated retrospectively. Changes in the HbA1c levels of 237 patients were analyzed after insulin initiation. Results The patients were divided into 4 groups according to the duration of diabetes at the time of insulin initiation: ≤3 years, 4 to 6 years, 7 to 9 years, or ≥10 years. Patients with a diabetes duration of ≤3 years were more frequently hospitalized at the time of insulin initiation, had a higher HbA1c level before insulin initiation and a lower HbA1c level at 1 year after insulin initiation and exhibited significant decreases in HbA1c at 1, 3, or 5 years after insulin initiation than those in the other 3 groups with longer durations of diabetes. In the group receiving 4 insulin injections per day, the reduction in HbA1c after 5 years of treatment was larger in patients with a diabetes duration at the time of insulin initiation of ≤3 years than in those with a duration of 7 to 9 years or ≥10 years. Conclusion Our results suggested that an earlier initiation of insulin therapy was crucial for sustaining glycemic control in Japanese patients with type 2 diabetes, particularly in those with a history of obesity or receiving multiple insulin injections daily.

The Usage of Type 2 Diabetes Medication for Outpatients at the Ministry of Public Security Traditional Medicine Hospital

This study aimes to analyse the usage of type 2 diabetes medication for outpatients at the Ministry of Public Security Traditional Medicine Hospital and to rate their adherence to the treatment. In this study, Type 2 diabetic patients were treated as outpatients and managed for at least 12 months at the clinic of the hospital. The results show that after 12 months of treatment, the average fasting blood glucose value decreased from 7.6 ± 1.76 mmol/l to 7.42 ± 1.81 mmol/l and the percentage of the patients either with blood glucose changes or reached the FPG target, increased from 38.3% to 70.0%, a statistically significant difference with p &lt;0.05. After 6 months of treatment from the time of T-6 to T0, HbA1c index decreased by 7.1 ± 1.0 to 6.4 ± 0.9% and the percentage of the patients either with HbA1C value changes or achieved the target, increased from 50.0% to 75.0%. The percentage of the patients who had good compliance was 60.8%. With an additional drug in the regimen, the adherence reduced by 29% (OR = 0.71; 95% CI 0.56 - 0.89; p = 0.002). The adherence of the 1-year-older patients decreased by 9% (OR = 0.91; 95% CI 0.84 - 0.97; p = 0.03). The study concludes that most of the patients received stable treatment; the regimens promoted maximum therapeutic effect. The two factors affecting the level of compliance of the patients with the drug were the age and the number of diabetes medicines used in the application.&#x0D; Keywords&#x0D; Type 2 diabetes, adherence to treatment, outpatients.&#x0D; References&#x0D; [1] Association. American Diabetes, Standards of medical care in diabetes - 2018, https://diabetesed.net/wp-content/uploads/2017/12/2018-ADA-Standards-of-Care.pdf, 2018 (accessed 25 May 2019).[2] A. Jafarian-Amirkhizi, A. Sarayani, K. Gholami, M. Taghizadeh-Ghehi, K. Heidari, A. Jafarzadeh-Kohneloo, D.E.Morisky, Adherence to medications, self-care activity, and HbA1c status among patients with type 2 diabetes living in an urban area of Iran, J Diabetes Metab Disord. 17(2) (2018) 165-172. https://doi: 10.1007/s40200-018-0356-4.[3] D.E. Morisky, M.R. Di Matteo, Improving the measurement of self-reported medication nonadherence: Response to Authors, J Clin Epidemiol. 64(3) (2011) 255-257; discussion 258-63. https:// doi: 10.1016/j.jclinepi.2010.09.002.[4] Y. Tominaga, T. Aomori, T. Hayakawa, D.E. Morisky, K. Takahashi, M. Mochizuki, Relationship between medication adherence and glycemic control in Japanese patients with type 2 diabetes. Pharmazie. 73(10) (2018) 609-612. https://doi: 10.1691/ph.2018.8587. [5] M.C. Govern Andrew, T. Zayd, Systematic review of adherence rates by medication class in type 2 diabetes: a study protocol, BMJ Open, 6(2) (2016) e010469. https://doi: https://doi: 10.1136/bmjopen-2015-010469.[6] M. Tiktin, S. Celik, Understanding adherence to medications in type 2 diabetes care and clinical trials to overcome barriers: a narrative review, Curr Med Res Opin. 32(2) (2016) 277-287. https:// doi: https:// doi: 10.1185/03007995.2015.1119677.&#x0D; &#x0D; &#x0D;

148-OR: IDegLira Improves Glycemic Control in Japanese Patients with Type 2 Diabetes (T2D) Uncontrolled on Premixed Insulin Therapy

Diabetes management is moving towards choosing therapies that reduce treatment burden, risk of hypoglycemia and weight gain. DUAL VII showed that IDegLira, a fixed-ratio insulin degludec (degludec)/liraglutide combination, had non-inferior A1C lowering, lower hypoglycemia rates, no weight gain and less treatment burden vs. basal-bolus therapy. In contrast, there are no trial data on the efficacy and safety of switching patients (pts) from premixed insulin therapy (with basal and bolus components) to a fixed-ratio combination such as IDegLira. DUAL II Japan (NCT02911948) - a 26 week phase 3a multicenter, randomized, double-blind, treat-to-target trial - compared the efficacy and safety of IDegLira vs. ≤50 U degludec in 210 Japanese pts with uncontrolled T2D (A1C 7.5-11.0%) on 20-50 U basal or premixed insulin therapy + metformin ± an oral antidiabetic drug. Primary analysis confirmed superior change in A1C with IDegLira vs. degludec ≤50, and post hoc analyses found the treatment effect was independent of insulin type at baseline (basal or premixed; interaction test, p=0.5229). This post hoc evaluation describes novel data in a subset of 39 pts who switched from premixed insulin to IDegLira. Mean (standard deviation [SD]) A1C was 8.3% (0.73) at baseline and 6.7% (0.93) at Week 26. Mean (SD) body weight reduced by 1.5 (2.9) kg. Daily insulin dose was 14.1 (3.4) U at baseline and 34.2 (11.5) U at Week 26. Rate of hypoglycemic events (defined as severe or plasma glucose &amp;lt;56 mg/dL) was 2.6 events/patient-year of exposure (52 events in 17 pts). No pts withdrew. This post hoc study is the first to evaluate the switch from premixed insulin to IDegLira, in pts with uncontrolled T2D. IDegLira initiation resulted in improved A1C and weight loss with most pts not experiencing hypoglycemic events. This study offers insight into the effectiveness and safety of switching pts from premixed insulin therapy to IDegLira, and provides a support for further investigation into this transition. Disclosure H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited. B.F. Agner: Employee; Self; Novo Nordisk A/S. A. Doshi: Advisory Panel; Self; Pfizer Inc. Employee; Self; PrimeCare Medical Group. R. Grøn: Employee; Self; Novo Nordisk A/S. M.F. Ranthe: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. L.K. Billings: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S

854-P: Personality, Self-Management Behaviors, and Glycemic Control among Japanese Patients with Type 2 Diabetes Mellitus (T2DM)

Diabetes self-management is an essential part of diabetes care. Although several personality traits were reportedly associated with self-management behaviors or glycemic control in Western countries, clinical evidence of such an association is still sparse, especially among Asian patients with diabetes. Thus, we aimed to clarify the associations among personality, self-management behaviors, and glycemic control in Japanese patients with T2DM. Analyzed were 510 Japanese patients with T2DM (62.2 ± 11.2 y; 57% men) with available information on personality (assessed by NEO Five-Factor Inventory), diabetes self-management activities (assessed by the Japanese version of Summary of Diabetes Self-Care Activities), body mass index (BMI), and HbA1c. Coefficient of correlation indicated that those with high scores for neuroticism, as well as low scores for conscientiousness, had lower levels of diet (neuroticism r = -0.14, P&amp;lt;0.05; conscientiousness r = 0.14, P&amp;lt;0.001) and physical activity (neuroticism r = -0.13, P&amp;lt;0.05; conscientiousness r = 0.15, P&amp;lt;0.001) self-management than those without such scores. There was no significant trend in medication adherence according to personality traits. Structural equation modeling showed that HbA1c was negatively associated with conscientiousness (standardized path coefficients = -0.024, P&amp;lt;0.05). Conscientiousness was significantly associated with higher self-management scores on diet and physical activity and was directly and indirectly (via BMI) related to HbA1c levels. Our results showed that Japanese patients with high conscientiousness levels had better glycemic control via favorable adherence to diet and physical activity but not medication adherence than those with lower conscientiousness levels. Evaluation of personality traits could identify patients likely to exhibit good/poor diabetes self-management care. This might be helpful in providing effective and efficient patient education. Disclosure S.Y. Morikawa: None. K. Fujihara: None. M. Hatta: None. Y. Takeda: None. D. Ishii: None. J. Yachida: None. C. Horikawa: None. M. Kato: None. H. Maegawa: Research Support; Self; Antares Pharma, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kowa Pharmaceutical Europe Co. Ltd., Kyowa Hakko Kirin Co., Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited.

Effects of Long-term Treatment of Linagliptin on Glycemic Control in Japanese Patients with Type 2 Diabetes

Effects of Long-term Treatment of Linagliptin on Glycemic Control in Japanese Patients with Type 2 Diabetes

Impact of age at menarche on obesity and glycemic control in Japanese patients with type 2 diabetes: Fukuoka Diabetes Registry.

Aims/IntroductionA younger age at menarche is associated with obesity and type 2 diabetes in adult life. The impact of early‐onset menarche on obesity and glycemic control in type 2 diabetes has not been investigated. The present study examined the relationship between age at menarche and obesity and glycemic control in type 2 diabetes.Materials and MethodsA total of 2,133 patients with type 2 diabetes aged ≥20 years were divided into groups according to age at menarche (≤11, 12, 13, 14 and ≥15 years). A retrospective cohort study examined the association of menarcheal age with adiposity and hemoglobin A1c.ResultsAge at menarche was inversely associated with body mass index (BMI) and abdominal circumference (P < 0.001). Each 1‐year decrease in age at menarche was associated with a 0.25‐kg/m2 and 0.6‐cm increase in BMI and abdominal circumference, respectively, using a multivariate‐adjusted model. Odds ratios for obesity and abdominal obesity significantly increased in participants with age at menarche ≤11 years after multivariable adjustments when age at menarche of 13 years was used as the reference (odds ratio 1.95, 95% CI 1.33–2.88, odds ratio 1.95, 95% CI 1.32–2.87, respectively). Younger age at menarche was significantly associated with higher hemoglobin A1c (P < 0.001); however, the association was not statistically significant after adjusting for BMI.ConclusionsAge at menarche of ≤11 years was associated with obesity after adjusting for confounding factors, and poor glycemic control associated with high BMI in type 2 diabetes. Age at menarche should be considered during clinical assessments.

N-3 polyunsaturated fatty acids improve lipoprotein particle size and concentration in Japanese patients with type 2 diabetes and hypertriglyceridemia: a pilot study

BackgroundPatients with type 2 diabetes are at high risk for cardiovascular disease. Although hydroxymethylglutaryl-CoA reductase inhibitors (statins) can reduce cardiovascular events, residual risk remains even after target low-density lipoprotein cholesterol (LDL-C) levels have been achieved. Lipoprotein particle size and fraction changes are thought to contribute to such risks. The purpose of this study was to evaluate the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs), predominantly eicosapentaenoic acid and docosahexaenoic acid, on lipoprotein particle size, concentration, and glycemic control in Japanese patients with type 2 diabetes and hypertriglyceridemia.MethodsThis was a multicenter, prospective, open-label, single arm study. We enrolled 14 patients with type 2 diabetes and hypertriglyceridemia treated with statins and dipeptidyl peptidase-4 inhibitors with glycated hemoglobin (HbA1c) < 8.0%, LDL-C < 120 mg/dL, and fasting triglyceride ≥150 mg/dL. After a 12-week observation period, they were treated with 4 g/day n-3 PUFAs for 12 weeks. Lipoprotein particle sizes, concentrations, lipoprotein insulin resistance (LPIR) scores, lipid profiles, HbA1c, and fasting plasma glucose (FPG) were measured before and after treatment. Lipoprotein profiles were measured by nuclear magnetic resonance spectroscopy. Data were analyzed using Wilcoxon signed-rank tests.ResultsConcentrations of total cholesterol (P < 0.001), LDL-C (P = 0.003), and triglyceride (P < 0.001) decreased following n-3 PUFA administration. N-3 PUFAs decreased the size of very low-density lipoprotein (VLDL; P < 0.001) particles, but did not affect LDL or high-density lipoprotein (HDL) particles. The concentration of large LDL increased, whereas small LDL decreased, causing the large to small LDL ratio to increase significantly (P = 0.042). Large VLDL and chylomicron concentrations significantly decreased, as did the large to small VLDL ratio (all P < 0.001). FPG levels unchanged, whereas HbA1c levels slightly increased. LPIR scores improved significantly (P = 0.001).ConclusionsN-3 PUFAs partly improved atherogenic lipoprotein particle size and concentration, and produced less atherogenic lipoprotein subclass ratios in patients that achieved target LDL-C levels and glycemic control. These results suggest that n-3 PUFAs may reduce residual cardiovascular risk factors in statin-treated patients with type 2 diabetes and hypertriglyceridemia.Trial registrationThe study was registered at UMIN-ID: UMIN000013776.

Association between nighttime sleep duration, midday naps, and glycemic levels in Japanese patients with type 2 diabetes

ObjectivesTo clarify the relationship between nighttime sleep duration, midday naps, and glycemic control in Japanese patients diagnosed with type 2 diabetes (n = 355) or impaired glucose tolerance (n = 43). MethodsA total of 398 patients completed a self-administered questionnaire on sleep duration/quality and were divided into five groups according to their self-reported nighttime sleep duration: <5 h, 5–6 h, 6–7 h, 7–8 h, and >8 h. Each group was further divided into two subgroups each according to the presence or absence of midday naps. Poor glycemic control was defined as HbA1c ≥ 7.0%. ResultsShort nighttime sleep (<5 h), poor sleep induction, daytime sleepiness, and low sleep satisfaction were associated with high HbA1c levels. HbA1c was higher in the short nighttime sleep/no nap group than in non-nappers with different nighttime sleep duration, whereas the short nighttime sleep/nap group showed similar HbA1c levels to the other nap subgroups. In multivariate logistic regression models, after adjusting for a number of potential confounders, short (<5 h) nighttime sleep without nap was significantly associated with poor glycemic control compared with 6–7 h nighttime sleep without nap (OR [95% CI]: 7.14 [2.20–23.20]). However, taking naps reduced this risk for poor glycemic control in short sleepers. Other risk factors for poor glycemic control were low sleep satisfaction (1.73 [1.10–2.70]) and poor sleep induction (1.69 [1.14–2.50]). ConclusionsPoor sleep quality and quantity could aggravate glycemic control in type 2 diabetes. Midday naps could mitigate the deleterious effects of short nighttime sleep on glycemic control. Clinical trials registrationUMIN 000017887.