Glycemic Control In Japanese Patients Research Articles

Satisfaction of switching to combination therapy with lixisenatide and basal insulin in patients with type 2 diabetes receiving multiple daily insulin injection therapy: A randomized controlled trial.

Aims/IntroductionWe compared the satisfaction levels of patients with type 2 diabetes undergoing combination therapy with lixisenatide (LIX) and basal insulin with that of patients undergoing multiple daily insulin injection (MDI) therapy.Materials and MethodsThe study was a 12‐week open‐label, randomized, multicenter, controlled trial. Participants were Japanese patients with type 2 diabetes receiving MDI for >3 months. Patients were randomly assigned to each treatment cohort: (i) a group that continued MDI (MDI group); and (ii) a group that switched from MDI to combination therapy with LIX and basal insulin (LIX group). The primary outcome was change in Diabetes Treatment Satisfaction Questionnaire scores from baseline to 12 weeks between these two groups. Key secondary outcomes were glycated hemoglobin and body weight changes.ResultsA total of 31 patients were initially enrolled in the study, and 26 of them completed the study. The change in Diabetes Treatment Satisfaction Questionnaire scores in the LIX group was significantly greater compared with that in the MDI group. Mean changes in glycated hemoglobin levels were −0.05 ± 0.37% in the MDI group and 0.04 ± 0.38% in the LIX group (P = 0.36). Mean changes in body weight were +0.6 ± 1.8 kg in the MDI group and −2.5 ± 1.8 kg in the LIX group (P < 0.01).ConclusionsSwitching from MDI to combination therapy with LIX and basal insulin improved satisfaction levels while maintaining glycemic control in Japanese patients with type 2 diabetes.

Eating glutinous brown rice twice a day for 8 weeks improves glycemic control in Japanese patients with diabetes mellitus

Objective:We recently reported that eating glutinous brown rice (GBR) for 1 day improved the whole-day glucose profile and postprandial plasma glucose level compared with eating white rice (WR) or standard brown rice. However, it was unknown whether eating GBR could maintain improvement of glycemic control for a longer period. Therefore, we evaluated the effect of GBR intake for 8 weeks on glycemic control in outpatients with diabetes mellitus.Methods:This was an open-label randomized crossover study in outpatients with type 2 diabetes. Among the 18 subjects registered in this study, 2 were excluded from analysis. After a 1-week observation period while eating WR twice a day, the patients were randomly assigned to two groups. One group ate GBR as a staple food twice a day for 8 weeks and then switched to WR for the next 8 weeks, while the other group ate WR first and then switched to GBR. A mixed meal tolerance test was performed at baseline and after 8 and 16 weeks of dietary intervention to evaluate plasma glucose and serum C-peptide.Results:None of the subjects failed to complete the study because of disliking the taste of GBR. Hemoglobin A1c (7.5–7.2%, P=0.014) and glycoalbumin (20.4–19.4%, P=0.029) both decreased significantly when the patients were eating GBR. Additionally, the 30-min postprandial plasma glucose level (194–172 mg dl−1, P=0.031) and the incremental area under the concentration vs time curve of serum C-peptide (31.3–22.1 ng min ml−1, P=0.023) during the mixed meal tolerance test were also decreased significantly by intake of GBR. In contrast, there were no changes of glycemic control during the WR period.Conclusions:We confirmed that GBR was well tolerated for 8 weeks and improved glycemic control in patients with type 2 diabetes.

Unique hemoglobin A1c level distribution and its relationship with mortality in diabetic hemodialysis patients

Diabetic hemodialysis patients with hemoglobin A1c (HbA1c) levels below 6.5% and over 8.0% face a higher mortality risk. To determine the optimal glycemic control in Japanese patients, we examined the association between HbA1c and mortality in 2,300 Japanese diabetic patients on maintenance hemodialysis with HbA1c levels determined at enrollment in the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS) phases 2-5, using Cox regression analysis with adjustment for baseline age, sex, dialysis vintage, 12 general comorbidities, hemoglobin, albumin and creatinine levels, and insulin use; stratification by JDOPPS phase; and facility clustering taken into account. Overall, 54% of patients had HbA1c levels under 6.0, including 14% with HbA1c levels under 5.0. Insulin or oral diabetes medications were used less frequently in patients with higher HbA1c levels. The dependence of mortality on HbA1c level was U shaped. When the group with the lowest mortality (HbA1c 6.0-7.0) was used as a reference, the hazard ratios for HbA1c categories under 5.0, 5.0-6.0, 7.0 to under 8.0, and 8.0 and greater were, respectively, 1.56 (95% confidence interval, 1.05-2.33), 1.26 (0.92-1.71), 1.23 (0.79-1.89), and 2.10 (1.32-3.33) in the adjusted model. The HbA1c level was not associated with self-reported hypoglycemic episodes in JDOPPS phase 5. The HbA1c levels in diabetic hemodialysis patients differ considerably between Japan and those reported from Western countries. Thus, our findings highlight the importance of domestic guidelines for glycemic control by race and country.

Long-Term Effect of Alogliptin on Glycemic Control in Japanese Patients With Type 2 Diabetes: A 3.5-Year Observational Study.

BackgroundThe goal of the current study was to investigate the long-term effects (after 3 years or more) of alogliptin on glycemic control in Japanese patients with type 2 diabetes.MethodsWe retrospectively studied the effect of alogliptin on glycemic control in the patients with type 2 diabetes who had participated in our previous 3-month study and who continued to take alogliptin for at least 36 months.ResultsThe mean duration of alogliptin treatment was 42.8 ± 2.2 months. In all 39 patients, a significant reduction in hemoglobin A1c (HbA1c) levels was noted between the baseline and final visit: 7.8±0.6% to 7.2±1.0% (P = 0.0001). A significant reduction in HbA1c levels was found in a subgroup of patients who did not change their anti-diabetic drugs or did decrease the dose of their sulfonylureas (SUs) or did change to a lower strength repaglinide (n = 32): 7.7±0.6% to 7.2±1.0% (P = 0.0005). A significant decrease in low-density lipoprotein cholesterol (LDL-C) levels was observed in all of the patients that had LDL-C levels determined (P = 0.0406) (n = 37), and in a subgroup of patients who had not taken either statins, fibrates, or pioglitazone, or who had taken one or more of these drugs but the doses were not changed during the observation period (P = 0.0250) (n = 27).ConclusionThe current study found that alogliptin performed well for glycemic control when evaluated by HbA1c levels in a long-term observation period exceeding 3 years in Japanese patients with type 2 diabetes. Alogliptin may also decrease circulating LDL-C levels with long-term use.

Effect of Switching From an Anti-Diabetic Loose Dose Combination to a Fixed Dose Combination Regimen at Equivalent Dosage for 6 Months on Glycemic Control in Japanese Patients With Type 2 Diabetes: A Pilot Study.

BackgroundPatients with type 2 diabetes mellitus often take multiple anti-diabetic drugs for a long period. Fixed dose combination (FDC) therapy is expected to improve drug adherence for patients with diabetes. The effect of switching from a loose dose combination (LDC) regimen to an FDC regimen at equivalent dosage on glycemic control has not been evaluated fully. Therefore, we investigated the effect of switching from LDC to FDC at equivalent dosage for 6 months on glycemic control in Japanese patients with type 2 diabetes.MethodsThirty-eight Japanese patients with type 2 diabetes who were taking anti-diabetic drugs including pioglitazone + metformin, pioglitazone + alogliptin, or pioglitazone + glimepiride were enrolled. These drugs were switched to an FDC of Metact®, Liobel® or Sonias®, respectively, at equivalent dosage. Other anti-diabetic drugs and units of insulin were not changed during the study if possible. HbA1c and body weight were measured 0, 2, 4 and 6 months after switching from an LDC to FDC. We also conducted a questionnaire survey 2 months after the start of the FDC regimen.ResultsHbA1c levels at 2, 4, and 6 months were not significantly changed compared with prior to switching from an LDC to FDC regimen. Moreover, 74.2% of patients considered decreasing the number of drugs to be “very good” or “good”.ConclusionHbA1c levels did not differ between patients receiving LDC and FDC therapy at equivalent dosage in this study.

Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin on Atherosclerosis, β-Cell Function, and Glycemic Control in Japanese Patients with Type 2 Diabetes Mellitus Who are Treatment Naïve or Poorly Responsive to Antidiabetes Agents: A Multicenter, Prospective Observational, Uncontrolled Study

BackgroundSitagliptin, a dipeptidyl peptidase-4 inhibitor, is widely used in patients with type 2 diabetes. However, the pleiotropic effects of sitagliptin is not well understood. ObjectiveTo assess the clinical efficacy and safety of sitagliptin on atherosclerosis, β-cell function, and glycemic control in Japanese patients with type 2 diabetes. MethodsA prospective observational study of 270 patients with type 2 diabetes mellitus was carried out. Patients (aged 64.3 [12.4] years, body mas index 25.2 [4.3]) with glycated hemoglobin >6.9% (52 mmol/mol) or fasting plasma glucose >130 mg/dL were treated with sitagliptin for 12 months. The primary end point was glycated hemoglobin level changes from baseline to 3 months. The secondary end points included changes in several biomarkers related to inflammation and β-cell function from baseline to 3 months, as well as changes in glycated hemoglobin level from baseline to 12 months. ResultsGlycated hemoglobin levels were significantly lower in patients treated with sitagliptin for 3 months than at baseline (8.1% [1.4%]–7.3% [1.2%]) (65 [16.9]–56 [13.1] mmol/mol]) (P < 0.0001), which continued after 12 months (7.4% [1.3%]) (56 [15.2] mmol/mol) (P < 0.0001). In addition, a marker of vascular-specific inflammation, pentraxin-3, and a marker of β-cell function (proinsulin/insulin ratio), respectively, were lower after treatment with sitagliptin for 3 months than at baseline (1.88 [0.78]–1.65 [0.63] ng/mL [P = 0.0038] and 0.20 [0.14]–0.17 [0.11] [P = 0.01], respectively). On the other hand, a biomarker reflecting whole body inflammation; that is, high-sensitivity C-reactive protein level, was unchanged. Adverse events occurred in 14 patients (5.18%). ConclusionsSitagliptin may have beneficial effects on vascular inflammation and β-cell function in Japanese patients with type 2 diabetes. Pentraxin-3 may be an early predictive marker for detecting the antiatherosclerotic effects of dipeptidyl peptidase-4.

Effects of GLP-1 Receptor Agonists on Glycemic Control in Japanese Patients With Type 2 Diabetes Mellitus

Effects of GLP-1 Receptor Agonists on Glycemic Control in Japanese Patients With Type 2 Diabetes Mellitus

Combination of liraglutide and sitagliptin therapy improves glycemic control in Japanese patients with type 2 diabetes mellitus

Combination of liraglutide and sitagliptin therapy improves glycemic control in Japanese patients with type 2 diabetes mellitus

Efficacy of switching from insulin glargine to insulin degludec in patients with type 1 diabetes: a 16-week retrospective study.

We retrospectively investigated the effect of switching from insulin glargine (IGlar) to insulin degludec (IDeg) on glycemic control in Japanese patients with type 1 diabetes mellitus. We also evaluated the dose of IDeg, and assessed weight gain and the risk of hypoglycemia after switching. Forty-five patients with type 1 diabetes were switched from IGlar (once daily or twice daily) to IDeg (once daily) during routine medical care. Data were collected for 16weeks after switching from IGlar to IDeg. The mean HbA1c (%) in weeks 4, 8, 12, and 16 was lower than it was in week 0 (8.0±1.0, 8.0±1.4, 7.9±1.1, 7.6±1.0 vs. 8.3±1.3%, p<0.01). The total basal insulin dose (TBD) was significantly lower after 16weeks of IDeg as compared to IGlar treatment (0.30±0.12 vs. 0.24±0.11U/kg/day, p=0.001). In the twice-daily IGlar group, TBD showed a significant decrease from 0.33±0.12 to 0.26±0.11U/kg/day (p<0.001) after switching to IDeg. In the once-daily IGlar group, TBD showed a slight but not significant decrease from 0.23±0.08 to 0.20±0.09U/kg/day (p=0.97). Hypoglycemic episodes were transiently increased, but the change was not significant. The blood glucose fluctuation was evaluated from self-monitoring data and the coefficient of variation (CV) was calculated. The CV showed only a minimal change from 48.3±17.1 to 48.6±14.2% at 12weeks after switching to IDeg (p=0.73). In conclusion, once-daily IDeg improved glycemic control in patients with type 1 diabetes compared to the control achieved with IGlar, without increasing the risk of hypoglycemia. When switching from IGlar (especially twice daily), it is recommended that the initial dose of IDeg should be reduced in order to decrease the risk of hypoglycemia.

Eating glutinous brown rice for one day improves glycemic control in Japanese patients with type 2 diabetes assessed by continuous glucose monitoring.

We investigated whether intake of non-glutinous brown rice (BR) or glutinous brown rice (GBR) for 1 day had an influence on the daily glucose profile measured by continuous glucose monitoring (CGM) when compared with intake of non-glutinous white rice (WR). A total of 37 inpatients with type 2 diabetes mellitus (T2DM) were recruited for a 3-day randomized triple cross-over trial in which they ate WR, BR, or GBR for 1 day each. One of the three types of rice was eaten at breakfast, lunch, and dinner on the first day, before switching to the other types on the second and third days. Each meal had the same energy content and the same side dishes. The main outcome measures were the blood glucose profile determined by continuous glucose monitoring (CGM) and the profile of serum C-peptide (CPR) for 3 hours after breakfast. A self-administered questionnaire was used to assess the palatability of each type of rice. According to the CGM data, the mean 24-hour glucose concentration was lowest with GBR (p<0.01). Serum Cpeptide showed no significant differences among the three diets. Regarding palatability, BR was assigned significantly lower scores than WR and GBR (p<0.05), while there was no difference between WR and GBR. GBR intake suppressed the whole-day glucose profile of patients with T2DM, mainly by reducing postprandial glucose excursion, and GBR was preferred over BR with respect to palatability. GBR may be worth adding to the diet of patients with T2DM.

Effect of Switching from Sulphonylurea to Repaglinide Twice or Three Times Daily for 4 Months on Glycemic Control in Japanese Patients with Type 2 Diabetes.

Objective Switching from sulfonylureas to repaglinide in patients with type 2 diabetes improves glycemic control; however, the optimal dosage has not been fully evaluated. We designed to show that repaglinide was equivalent to sulfonylurea in Japanese patients with type 2 diabetes. We herein evaluated whether we could switch from sulfonylureas to repaglinide twice or thrice daily in Japanese adult patients who had been treated with anti-diabetic drugs, including sulfonylureas, and whose conditions were moderately well-controlled. Methods A total of 78 patients taking less than half the Japanese maximum dose of sulfonylurea were randomized into three groups: 26 in group A (switching from sulfonylureas to taking 0.25 or 0.5 mg of repaglinide just before breakfast and dinner twice daily), 27 in group B (switching from sulfonylureas to taking 0.25 or 0.5 mg of repaglinide just before meals thrice daily), and 25 in group C (continuing to take sulfonylurea). Blood samples were collected at 0, 1, 2, 3, and 4 months following the initiation of the maintenance period. Results The HbA1c and glycoalbumin levels did not significantly differ among the three groups after 4 months of treatment. Conclusion With the assumption that 1 mg of glimepiride is equivalent to 1.25 mg of glibenclamide or 40 mg of gliclazide, the administration of repaglinide (0.44 mg/meal) twice and thrice daily is similar to the efficacy of sulfonylurea (glimepiride 1.63-1.98 mg/day) after four months of treatment in Japanese patients with moderately well-controlled type 2 diabetes (HbA1c, 7-7.5%).

Predictors for achieving target glycemic control in Japanese patients with type 2 diabetes after initiation of basal supported oral therapy using insulin glargine: sub-analysis of the ALOHA2 study, drug use surveillance in Japan.

We aimed to identify diabetes-related factors associated with achieving HbA1c <7.0% after the initiation of basal supported oral therapy (BOT) in insulin-naïve type 2 diabetes patients with an HbA1c value of ≥6.5% during the previous 4weeks, using data from Add-on Lantus® to Oral Hypoglycemic Agents 2 (ALOHA2) study, a 24-week observational study on Japanese type 2 diabetes patients. Patients were categorized into two groups: HbA1c <7.0% at the final evaluation point (at 24weeks or the last visit) as HbA1c-target-achieved; HbA1c ≥7.0% as target-not-achieved. Associations between baseline factors and HbA1c <7.0% achievement were explored using logistic regression. Of the 1520 patients in the study, 400 patients (26.3%) achieved HbA1c <7.0%. Patients with diabetes duration of <1year and between ≥1 and <2years [odds ratio (OR): 5.27, 95% confidence interval (CI): 1.13-24.51; OR: 3.77, 95% CI 1.19-11.93, respectively], those on one pre-study orally administered antidiabetic agent (OAD) (OR: 2.42, 95% CI 1.12-5.22), and those with absence of diabetic neuropathy (OR: 2.54, 95% CI 1.12-5.76) were more likely to achieve HbA1c <7.0% than those with duration of ≤15years, ≥4 pre-study OADs, and neuropathy, respectively. Achievement of HbA1c <7.0% among patients increased by approximately 20% for each 1% decrease in HbA1c level at baseline. Shorter diabetes duration, pre-study regimen of one OAD, absence of neuropathy, and lower HbA1c level at baseline were associated with achievement of HbA1c <7.0%, suggesting that earlier initiation of BOT leads to good HbA1c control in insulin-naïve Japanese type 2 diabetes patients, consistent with our early ALOHA study.

Comparative Efficiency of Sulfonylurea and/or Dipeptidyl Peptidase-4 inhibitor in Basal-Supported Oral Therapy in Japanese Patients with Type 2 Diabetes (JDDM39)

Basal-supported Oral Therapy (BOT), comprising treatment with oral antidiabetic drugs and once-daily injections of a long-acting insulin analog, is a convenient regimen. However, it sometimes fails to achieve satisfactory glycemic control because of uncontrolled hyperglycemia in the postprandial period. The aim of the present retrospective cohort study was to assess the efficiency of a sulfonylurea (SU) and/or a dipeptidyl peptidase-4 inhibitor (DPP-4i) on glycemic control in Japanese patients with type 2 diabetes mellitus (T2DM) who were receiving BOT. The 243 T2DM patients who started long-acting insulin added onto an SU and/or DPP-4i, with or without metformin, were followed-up for 6 months. Mean HbA1c levels in the SU, DPP-4i, and SU + DPP-4i groups decreased steadily from baseline by approximately 1% over the 6-month followed-up period. After 6 months, 57.4%, 51.6%, and 62.2% of patients in the SU, DPP-4i, and SU + DPP-4i groups, respectively, had continued on the same therapeutic regimen, and 15.2%, 18.5%, and 16.5% of patients, respectively, had achieved HbA1c levels <7.0%. The efficiency of BOT with SU, DPP-4i, and SU + DPP-4i was limited, but some patients (i.e. those with a lower body mass index and HbA1c) may benefit from these BOT regimens.

Effect of repaglinide, administered two or three times daily for 3 months, on glycaemic control in Japanese patients with type 2 diabetes mellitus.

To compare the efficacy, safety and compliance of repaglinide, administered either two or three times daily, regarding glycaemic control in patients with type 2 diabetes mellitus. Japanese adults with type 2 diabetes mellitus, who had been treated without sulphonylureas or glinides for >3 months, were randomly assigned to two groups to receive either 0.25 mg repaglinide, oral, twice daily (group A) or 0.25 mg repaglinide, oral, three times daily (group B). Glycosylated haemoglobin (HbA1c), glycoalbumin (GA) and 1,5-anhydroglucitol (1,5-AG) levels were measured at 0, 1, 2 and 3 months after treatment commenced. Out of 43 patients who enrolled (group A, n = 22; group B, n = 21), 33 patients completed the trial (group A, n = 16; group B, n = 17). No significant between-group differences in HbA1c, GA, or 1,5-AG levels were seen at 1-3 months. No severe hypoglycaemic episodes or other adverse events were observed. Minimal-dose repaglinide administered twice daily was similar in efficacy and safety to three-times-daily administration, in Japanese patients with type 2 diabetes mellitus. Administration of repaglinide twice daily could be an alternative regimen for patients who cannot take repaglinide three times daily.

Ipragliflozin improves glycemic control in Japanese patients with type 2 diabetes mellitus: the BRIGHTEN study

Ipragliflozin is a sodium–glucose co-transporter 2 inhibitor under clinical development for treating type 2 diabetes mellitus (T2DM). In this Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, 129 Japanese patients with T2DM were randomized to either 50 mg ipragliflozin (n = 62) or placebo (n = 67) once daily for 16 weeks. Hemoglobin A1c (HbA1c) levels decreased significantly from baseline to the end of treatment in the ipragliflozin group (−0.76 %) but increased in the placebo group (+0.54 %), resulting in a placebo-adjusted mean change from baseline of −1.24 % (P < 0.001). Fasting plasma glucose (FPG) levels also decreased significantly in the ipragliflozin group (−40.2 mg/dL) but not in the placebo group (+6.3 mg/dL). The changes in body weight (−2.31 kg vs. −1.03 kg, P < 0.001) and waist circumference (−1.61 cm vs. −0.41 cm, P = 0.028) from baseline to the end of treatment were significantly greater in the ipragliflozin group than in the placebo group. Treatment-emergent adverse events occurred in 53.2 % and 59.7 % of patients in the ipragliflozin and placebo groups, respectively. All of the events were mild to moderate in severity. Hypoglycemia (ipragliflozin vs. placebo 1.6 % vs. 0 %), genital infections (3.2 % vs. 0 %), and urinary tract infection (0 % vs. 1.5 %) were rare. In conclusion, treatment with 50 mg ipragliflozin once daily for 16 weeks achieved significant improvements in HbA1c, FPG, body weight, and waist circumference compared with placebo in Japanese patients with T2DM. Ipragliflozin was well tolerated with low rates of genital infection and hypoglycemia.

Effects of concomitant drugs on sitagliptin-mediated improvement in glycemic control in Japanese patients with type 2 diabetes

AimsWe investigated to clarify factors associated with the efficacy of sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor, for glycemic control including the confounding effect of concomitant drugs in patients with type 2 diabetes. MethodsWe included type 2 diabetes patients with HbA1c levels of ≥7% who were not under insulin treatment and were administered sitagliptin (50mg/day for 6 months). Reduction or discontinuation of insulin sensitizers was not permitted during the study period. Outcomes included HbA1c level variations and attaining a target HbA1c level of <7%. Associated factors with each outcome were examined using multivariate analysis. ResultsOf the 313 patients enrolled in this study, 147 (47.0%) attained HbA1c levels of <7%. High baseline HbA1c levels were associated with HbA1c level variations but inversely associated with attaining the target HbA1c level of <7%. Concomitant use of an insulin sensitizer and a α-glucosidase inhibitor and maintenance of the baseline dose of concomitant drugs were significantly associated with each outcome. ConclusionsOur results suggest that concomitant sitagliptin administration (50mg/day) will improve glycemic control if treatment is initiated before HbA1c levels deteriorate. Other medication should be continued at initiation of sitagliptin administration.

Monotherapy with the once weekly GLP-1 receptor agonist dulaglutide for 12 weeks in Japanese patients with type 2 diabetes: dose-dependent effects on glycaemic control in a randomised, double-blind, placebo-controlled study.

The aim of this study was to evaluate the dose-dependent effect of dulaglutide, a glucagon-like peptide-1 receptor agonist, on glycaemic control in Japanese patients with type 2 diabetes mellitus who were treated with diet/exercise or oral antidiabetic drug monotherapy. In this randomised, double-blind, placebo-controlled, parallel-group, 12-week study, patients received once weekly subcutaneous dulaglutide doses of 0.25, 0.5, or 0.75 mg (DU 0.25, DU 0.5, and DU 0.75, respectively) or placebo (n=36, 37, 35, and 37, respectively). The primary measure was change from baseline in glycated haemoglobin (HbA1c; %) at 12 weeks. Continuous variables were analysed using a mixed-effects model for repeated measures. Significant dose-dependent reductions in HbA1c were observed (least squares mean difference versus placebo [95% confidence interval]): DU 0.25=-0.72% (-0.95, -0.48), DU 0.5=-0.97% (-1.20, -0.73), and DU 0.75=-1.17% (-1.41, -0.93); p<0.001. Significant improvements in plasma glucose (PG), both fasting and average 7-point self-monitored blood glucose, were also observed with dulaglutide versus placebo (p<0.001). Dulaglutide was well-tolerated. Gastrointestinal adverse events (AEs) were more common in dulaglutide-treated patients, with nausea the most frequent (8 [5.5%]). Few dulaglutide-treated patients discontinued due to AEs (4 [3.7%]), and no serious AEs related to study medication occurred. Three patients (DU 0.5=1 and DU 0.75=2) reported asymptomatic hypoglycaemia (PG ≤70 mg/dL). The observed dose-dependent reduction in HbA1c and acceptable safety profile support further clinical development of dulaglutide for treatment of type 2 diabetes mellitus in Japan.

Factors associated with change in glycemic control in Japanese patients: Analyses of patients′ misperception

Factors associated with change in glycemic control in Japanese patients: Analyses of patients′ misperception

Effect of eating vegetables before carbohydrates on glucose excursions in patients with type 2 diabetes

The aim of this review was to evaluate whether eating vegetables before carbohydrates could reduce the postprandial glucose, insulin, and improve long-term glycemic control in Japanese patients with type 2 diabetes. We studied the effect of eating vegetables before carbohydrates on postprandial plasma glucose, insulin, and glycemic control for 2.5 y in patients with type 2 diabetes. The postprandial glucose and insulin levels decreased significantly when the patients ate vegetables before carbohydrates compared to the reverse regimen, and the improvement of glycemic control was observed for 2.5 y. We also compared the postprandial glucose and glucose fluctuations assessed by continuous glucose monitoring system for 72-h in patients with type 2 diabetes and subjects with normal glucose tolerance when subjects ate vegetables before carbohydrates and carbohydrates before vegetables in a randomized crossover design. The glycemic excursions and incremental glucose peak were significantly lower when the subjects ate vegetables before carbohydrates compared to the reverse regimen. This evidence supports the effectiveness of eating vegetables before carbohydrates on glucose excursions in the short-term and glycemic control in the long-term in patients with type 2 diabetes.

Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type2 diabetes mellitus.

We investigated the efficacy and safety of repaglinide as an add-on therapy for Japanese patients with type2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500mg/day, mainly) in addition to diet and exercise. In the 16-week multicenter, placebo-controlled, randomized, double-blind, parallel-group trial (the phaseIII study), patients with type2 diabetes mellitus with metformin monotherapy were randomly assigned to the repaglinide or placebo group. Thereafter, a 36-week, multicenter, uncontrolled, dose-titration method study was extended to a total duration of 52weeks (the long-term study). The primary end-point of each study was a change in glycated hemoglobin (HbA1c) from baseline. After 16weeks, mean reductions in HbA1c were significantly greater for the repaglinide group than for the placebo group (-0.98±0.72% vs 0.13±0.63%, P<0.001). In the long-term study, the mean change in HbA1c was -0.76±0.83%. The rate of adverse events was 60.6 and 50.0% in the repaglinide and placebo groups, respectively, in the phaseIII study, and 78.3% in the long-term study. Hypoglycemia was reported in 11.7, 0 and 13.3% of patients in the repaglinide group, placebo group and long-term study, respectively. Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA1c at week16 and in a significant long-term improvement in HbA1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with JapicCTI (nos. JapicCTI-101202 and JapicCTI-101203).