Sitagliptin added to voglibose monotherapy improves glycemic control in patients with type 2 diabetes

Aims/Introduction

Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control. The present multicenter, randomized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy (0.2–0.3 mg three times daily) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control (glycated hemoglobin ≥6.9% and <10.5%).

Materials and Methods

The present study had an initial 12‐week, double‐blind treatment period in which patients were randomized (1:1) to sitagliptin 50 mg/day (n = 70) or placebo (n = 63), followed by a 40‐week, open‐label treatment period during which all patients received sitagliptin 50 mg/day, that could have been increased to 100 mg/day for patients meeting predefined glycemic criteria.

Results

After 12 weeks, treatment with sitagliptin resulted in placebo‐subtracted mean changes from baseline in glycated hemoglobin (the primary end‐point), fasting plasma glucose and 2‐h postmeal glucose of –0.9%, –22.5 mg/dL and –51.3 mg/dL, respectively (all, P < 0.001). During the double‐blind period, adverse experiences were reported with similar frequency in both treatment groups, and the occurrences of hypoglycemia and gastrointestinal adverse experiences were low. In the open‐label period, sustained improvements in glycemic parameters were observed with sitagliptin treatment, and sitagliptin was generally well tolerated.

Conclusions

Sitagliptin added on to ongoing voglibose monotherapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control. This trial was registered with ClinicalTrails.gov (no. NCT00837577).     

Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

We investigated the efficacy and safety of repaglinide as an add‐on therapy for Japanese patients with type 2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500 mg/day, mainly) in addition to diet and exercise.

Materials and methods

In the 16‐week multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group trial (the phase III study), patients with type 2 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 52 weeks (the long‐term study). The primary end‐point of each study was a change in glycated hemoglobin (HbA_1c) from baseline.

Results

After 16 weeks, mean reductions in HbA_1c 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 HbA_1c 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 phase III 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.

Conclusions

Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA_1c at week 16 and in a significant long‐term improvement in HbA_1c 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).     

Short‐ and long‐term effect of sitagliptin after near normalization of glycemic control with insulin in poorly controlled Japanese type 2 diabetic patients

Aims/Introduction

The aim of the present study was to examine the short‐ and long‐term effect of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin in poorly controlled type 2 diabetic patients.

Materials and Methods

We consecutively enrolled a total of 30 type 2 diabetic patients whose glycated hemoglobin levels (National Glycohemoglobin Standardization Program) were ≥7.4%, stopped all oral antidiabetic drugs and started insulin therapy. When fasting plasma glucose levels became <140 mg/dL, we carried out the first oral glucose tolerance test (OGTT). After 1‐week sitagliptin treatment (50 mg/day), the second OGTT was carried out. Furthermore, we evaluated the long‐term efficacy of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin.

Results

After 1‐week sitagliptin treatment, the area under the curve of insulin was markedly increased, and the area under the curve of glucagon and glucose was markedly decreased. Duration of diabetes and insulin secretory capacity were correlated with the effect of sitagliptin. Furthermore, interestingly, near normalization of glycemic control with insulin therapy for 1–2 weeks brought out the long‐term effectiveness of sitagliptin on glucose tolerance for 24 weeks, which was not observed with other antidiabetic drugs.

Conclusions

These findings suggest that near normalization of glycemic control with insulin improves the clinical response to sitagliptin in poorly controlled type 2 diabetic patients.     

Addition of sitagliptin to ongoing metformin monotherapy improves glycemic control in Japanese patients with type 2 diabetes over 52 weeks

Aims/Introduction

The efficacy and safety of sitagliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, when added to metformin monotherapy was examined in Japanese patients with type 2 diabetes.

Materials and Methods

In this 52‐week, add‐on to metformin study, 149 patients were randomly assigned to receive sitagliptin 50 mg or placebo once daily in a double‐blind fashion for 12 weeks. Thereafter, all patients who completed the double‐blind period of the study received open‐label sitagliptin 50 mg once daily for 40 weeks, with the investigator option of increasing sitagliptin to 100 mg once daily for patients who met predefined glycemic thresholds.

Results

After 12 weeks of treatment, the mean change from baseline in glycated hemoglobin (HbA1c) significantly decreased with sitagliptin relative to placebo (between‐group difference [95% confidence interval] = −0.7% [−0.9 to −0.5] P < 0.001). At week 12, the mean changes in 2‐h post‐meal glucose (−2.6 mmol/L [−3.5 to −1.7]) and fasting plasma glucose (−1.0 mmol/L [−1.3 to −0.6]) also decreased significantly with sitagliptin relative to placebo (P < 0.001 for both). Significant improvements from baseline in glycemic control were also observed in the open‐label period through to week 52. There were no differences between treatment groups in the incidence of adverse events (AEs), including hypoglycemia and predefined gastrointestinal AEs (nausea, vomiting and diarrhea) during the double‐blind period, with similar findings in the open‐label period.

Conclusions

Over a period of 52 weeks, the addition of sitagliptin once‐daily to ongoing metformin therapy was efficacious and generally well tolerated in Japanese patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT00363948).     

Efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes switched from glinides

Aims/Introduction

The efficacy and safety of sitagliptin, a dipeptidyl peptidase (DPP)‐4 inhibitor, were compared with those of glinides in Japanese patients with type 2 diabetes.

Materials and Methods

The participants were 82 patients with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.0% and <10%) under treatment with glinides for glucose control. The participants were randomly assigned to a group (n = 44) receiving continuous treatment with glinides and a group (n = 38) switched to sitagliptin. Patients were followed for 12 weeks to evaluate glucose control. A meal tolerance test was carried out in weeks 0 and 12 to examine the pancreatic secretory response to postprandial hyperglycemia.

Results

The changes in HbA1c from week 0 to week 12 were −0.25 and −0.05% in the sitagliptin and glinide groups, respectively, with a significant improvement with sitagliptin. The differences in fasting plasma glucose (FPG), glycoalbumin and 1,5‐anhydroglucitol between the two groups were 14.2 mg/dL, 0.7% and 1.7 μg/mL, respectively, showing significant improvements with sitagliptin. In the meal tolerance test, glucose at 0 min was lower in the sitagliptin group; however, there were no differences in glucose elevation at 30 and 60 min compared with 0 min. Plasma insulin and glucagon secretion at week 12 were significantly lower than at baseline in the sitagliptin group. Adverse events including hypoglycemia did not differ between the groups.

Conclusions

FPG decreased and glucose control improved in patients who switched from glinides to sitagliptin. Sitagliptin decreased secretion of insulin and glucagon in a meal tolerance test compared with glinides, whereas the agents showed similar inhibition of postprandial hyperglycemia. This trial was registered with UMIN (UMIN‐CTR no. 000003479).     

Predictive factors of durability to sitagliptin: Slower reduction of glycated hemoglobin,older age and higher baseline glycated hemoglobin

Aims/Introduction

The goal of the present study was to evaluate predictive factors for good efficacy and durability to sitagliptin with ongoing metformin or metformin plus glimepiride therapy in a real practice situation. The present observational study was carried out over a 60‐week period and involved Korean patients with type 2 diabetes mellitus.

Materials and Methods

A total of 100 mg of sitagliptin were added once daily to the two most popular therapy regimens (group 1: metformin, group 2: metformin plus glimepiride). Before adding sitagliptin, mean initial glycated hemoglobin (HbA1c) levels were 7.8% (62 mmol/mol) and mean diabetes duration was 8.3 years.

Results

After 60 weeks, the mean change in HbA1c from baseline was −0.9% (−10 mmol/mol) in group 1 and −1.0% (−11 mmol/mol) in group 2. Decreased HbA1c levels were significantly associated with higher initial HbA1c and lower log‐transformed C‐peptide levels in a multivariate regression analysis. Logistic regression analysis showed that a sustained reduction in HbA1c levels after 12 weeks was significantly associated with older age (≥60 years), higher baseline HbA1c (group 1 ≥ 7.0% [53 mmol/mol], group 2 ≥ 7.5% [58 mmol/mol]) and slower reduction of HbA1c (ΔHbA1c <1.0% [11 mmol/mol]) in group 1 and group 2. In group 2, a higher ratio of reduction of postprandial glucose/reduction of fasting plasma glucose (ΔPPG/ΔFPG) during 12 weeks was also associated with a sustained reduction in HbA1c levels after 12 weeks.

Conclusions

The effects of sitagliptin lasted more than 12 weeks in older patients with a higher baseline HbA1c, and slower reduction of HbA1c during 12 weeks.     

Comparison of the efficacy of sitagliptin and glimepiride dose‐up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination

Aims/Introduction

The goal of the study was to examine the effects of sitagliptin dose‐up or glimepiride dose‐up in Japanese patients with type 2 diabetes who were controlled inadequately by sitagliptin and glimepiride in combination.

Materials and Methods

A multicenter, prospective, randomized, open‐label study was carried out in 50 patients with type 2 diabetes treated with sitagliptin and low‐dose glimepiride. The patients were randomly assigned to receive the addition of 50 mg/day sitagliptin or 0.5 mg/day glimepiride. The primary end‐point was the percentage change in glycated hemoglobin (HbA1c).

Results

During a follow‐up period, the difference in the percentage changes in HbA1c between the two groups was not significant (P = 0.13). However, HbA1c was significantly decreased by glimepiride dose‐up (P < 0.01 vs baseline), but not by sitagliptin dose‐up (P = 0.74). Univariate linear regression analyses showed that the percentage change in HbA1c was significantly associated with the serum level of arachidonic acid (AA) in both groups.

Conclusions

There was no significant difference in the HbA1c‐lowering effects between the two groups. However, a significant HbA1c‐lowering effect from baseline of glimepiride dose‐up was found, and the AA level showed a negative correlation with the decrease in HbA1c in the sitagliptin dose‐up group, but a positive correlation in the glimepiride dose‐up group. These findings suggest that the AA level is associated with HbA1c reduction in response to dose‐up with these drugs in patients with type 2 diabetes in a combination therapy with sitagliptin and glimepiride. This trial was registered with UMIN (no. 000009544).     

Appropriate physical activity and dietary intake achieve optimal metabolic control in older type 2 diabetes patients

Aims/Introduction

The aim of the present study was to investigate an appropriate level of physical activity and optimal dietary intake in older type 2 diabetes patients.

Materials and Methods

The cross‐sectional study enrolled 210 older type 2 diabetes patients. Participants were interviewed to obtain information on physical activity, 24‐h dietary recall and typical weekly dietary patterns. Anthropometric measurements, and biochemical analysis of blood and urine were determined.

Results

Moderate physical activity (either moderate leisure‐time physical activity or moderate physical activity level) and diet with protein intake of ≥0.8 g/kg/day were associated with lower glycated hemoglobin and triglyceride, higher high‐density lipoprotein, lower waist circumference, body mass index and body fat, as well as better serum magnesium and albumin levels in older diabetic patients. In contrast, inadequate protein intake was correlated with higher glycated hemoglobin, triglyceride, body fat percentage, waist circumference and body mass index. In addition, high physical activity with inadequate protein and magnesium intake might exacerbate magnesium deficiency, resulting in poor glycemic control in older diabetic patients. Furthermore, low physical activity and inadequate protein intake were linked with poor glycemic control, and lower high‐density lipoprotein, and higher triglyceride, body fat percentage, waist circumference and body mass index.

Conclusions

Moderate physical activity and adequate dietary protein intake (≥0.8 g/kg/day) might be the optimal recommendation for better metabolic control in older adults with type 2 diabetes.     

Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus

Introduction

The aim of the present study was to determine the effect of sitagliptin on microalbuminuria in patients with type 2 diabetes mellitus.

Materials and Methods

A total of 85 patients with type 2 diabetes mellitus (age >20 years, <80 years, hemoglobin A1c [HbA1c] <8.4%) were randomized to patients taking sitagliptin 50 mg or other oral glucose‐lowering agents. The following parameters were evaluated at 0, 3 and 6 months after the treatment: bodyweight, blood pressure, HbA1c, fasting plasma glucose, fasting plasma insulin, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate and urinary albumin excretion. The primary outcome was changes in urinary albumin excretion at 6 months.

Results

Significant and comparable falls in HbA1c and fasting plasma glucose were found in both groups. However, sitagliptin significantly reduced urinary albumin excretion within 6 months, especially in patients with high urinary albumin at baseline. A total of 27 patients with normoalbuminuria showed a reduction in urinary albumin excretion, suggesting that sitagliptin prevents the development of albuminuria. A total of 15 patients with albuminuria showed a reduction in urinary albumin excretion, suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy. There was a significant correlation between improvement of proteinuria and that of diastolic blood pressure.

Conclusions

The results suggested that sitagliptin improved albuminuria, in addition to improving glucose. The mechanism of the reduction of albuminuria by sitagliptin could be a direct effect, as well as an increase in active glucagon‐like peptide‐1, independently affecting blood pressure, bodyweight and glucose metabolism. This trial was registered with the University Hospital Medical Information Network (UMIN no. #000010871).     

Changes in oral antidiabetic prescriptions and improved glycemic control during the years 2002–2011 in Japan (JDDM32)

Aims/Introduction

Six kinds of oral antidiabetic drugs (OADs), including the new dipeptidyl peptidase 4 (DPP‐4) inhibitors, are available. The present study aimed to define trends within the prescribing patterns of OADs, as well as changes in glycemic control in Japan over a 10‐year period from 2002 to 2011.

Materials and Methods

We carried out a cross‐sectional study using data of type 2 diabetes mellitus patients from 24 clinics for 2002, 2005, 2008 and 2011. OAD use was analyzed combined with clinical data.

Results

Sulfonylureas (SUs) were the most commonly used OAD, but their use for monotherapy markedly decreased over the study period. Biguanides (BGs) were the second most commonly used OAD, and their prescribing rate increased both for mono‐ and combination therapy. DPP‐4 inhibitors (DPP‐4I), released in 2009, were the third most commonly prescribed OAD in 2011 both for mono‐ and combination therapy. Among combination therapies, two OADs were mostly prescribed, but the use of three OADs and four OADs in 2011 was two‐ and 14.8‐fold those in 2002. These trends were accompanied by an improvement in average glycated hemoglobin from 7.5 ± 1.2% in 2002 to 7.1 ± 0.9% in 2011.

Conclusions

The OAD prescribing trend has moved away from monotherapy with SUs and toward combination therapies to achieve better glycemic control. Increased use of BGs and DPP‐4I was predominant in 2011. These trends were accompanied by an improvement of the glycated hemoglobin level.     

Reward‐based,task‐setting education strategy on glycemic control and self‐management for low‐income outpatients with type 2 diabetes

Aims/Introduction

The purpose of the study was to determine the feasibility and effect of a reward‐based, task‐setting strategy for low‐income outpatients with type 2 diabetes.

Materials and Methods

Indigent diabetes outpatients without glucometers were eligible to participate in this trial. A total of 132 cases were randomly recruited. Participants in group B used glucometers for self‐monitoring at no cost. Group A participants could keep the glucometers only if the glycosylated hemoglobin level declined compared with the baseline visit; for those not achieving a reduction in the glycosylated hemoglobin level, the glucometers would have to be returned. Group C served as the control group without self‐monitoring setout. Diabetes education was provided to all groups. Metabolic indices and self‐management were evaluated after 6 months of follow up.

Results

Group A had a significant decline in the glycosylated hemoglobin level (−0.97%) and medical costs (−159 yuan) compared with the baseline visit, whereas groups B and C had a decrease in the glycosylated hemoglobin levels alone (−0.62 and −0.57%, respectively). The body mass index did not change significantly in any group. There was a statistical difference in the glycosylated hemoglobin level of group A compared with groups B and C. Self‐management in group A improved the outcome relative to groups B and C.

Conclusions

This preliminary evidence suggests that the program is feasible, acceptable for improving patient self‐management, and cost‐effective in reducing the glycosylated hemoglobin level and medical costs.     

Tolerability,effectiveness and predictive parameters for the therapeutic usefulness of exenatide in obese,Korean patients with type 2 diabetes

Aims/Introduction

We assessed the tolerability, effectiveness and predictive parameters for the therapeutic usefulness of exenatide in obese Korean participants with type 2 diabetes. We also evaluated the characteristics of participants who respond adequately to glucagon‐like peptide‐1 (GLP‐1) analog therapy in terms of glycated hemoglobin (HbA1c) level reductions and weight loss.

Materials and Methods

This prospective, observational, single‐arm (exenatide b.i.d. in combination with both metformin and sulphonylurea), open‐label study of GLP‐1 analog treatment with close monitoring of metabolic parameters and weight changes was carried out for up to 22 weeks.

Results

Of the 110 enrolled obese participants, 37 participants dropped out during the 22‐week treatment period. A total of 73 participants completed the study (median age 55.0 years, interquartile range 44.0–65.0). The median duration of diabetes was 8.0 years (interquartile range 3.5–12.5) with a mean HbA1c value of 7.6% (interquartile range 7.00–8.55). The median body mass index was 30.78 kg/m² (interquartile range 27.89–33.92). After 22 weeks, median changes from baseline for HbA1c levels and weight were −0.7% and −3.0 kg, respectively, which were significant. No severe hypoglycemic events were observed. Multivariate regression analysis showed that C‐peptide values were a significant independent predictor for a reduction in HbA1c levels (β = 0.865, P = 0.018) with exenatide BID in combination with both sulphonylurea and metformin in obese Korean participants with type 2 diabetes and insulin naïveté.

Conclusions

Clinical and laboratory parameters, such as insulin naïveté and preserved β‐cell function, should be taken into consideration as important factors in the choice of GLP‐1 analog when predicting GLP‐1 analog responsiveness. This trial was registered with the local committee at Yonsei University in Korea (4‐2011‐0032).     

Postprandial C‐peptide to glucose ratio as a predictor of β‐cell function and its usefulness for staged management of type 2 diabetes

Aims/Introduction

Type 2 diabetes is characterized by progressive deterioration of β‐cell function. Recently, it was suggested that the C‐peptide‐to‐glucose ratio after oral glucose ingestion is a better predictor of β‐cell mass than that during fasting. We investigated whether postprandial C‐peptide‐to‐glucose ratio (PCGR) reflects β‐cell function, and its clinical application for management of type 2 diabetes.

Materials and Methods

We carried out a two‐step retrospective study of 919 Korean participants with type 2 diabetes. In the first step, we evaluated the correlation of PCGR level with various markers for β‐cell function in newly diagnosed and drug‐naïve patients after a mixed meal test. In the second step, participants with well‐controlled diabetes (glycated hemoglobin <7%) were divided into four groups according to treatment modality (group I: insulin, group II: sulfonylurea and/or dipeptityl peptidase IV inhibitor, group III: metformin and/or thiazolidinedione and group IV: diet and exercise group).

Results

In the first step, PCGR was significantly correlated with various insulin secretory indices. Furthermore, PCGR showed better correlation with glycemic indices than homeostatic model assessment of β‐cell function (HOMA‐β). In the second step, the PCGR value significantly increased according to the following order: group I, II, III, and IV after adjusting for age, sex, body mass index and duration of diabetes. The cut‐off values of PCGR for separating each group were 1.457, 2.870 and 3.790, respectively (P < 0.001).

Conclusions

We suggest that PCGR might be a useful marker for β‐cell function and an ancillary parameter in the choice of antidiabetic medication in type 2 diabetes.     

Association of glycated albumin with the presence of carotid plaque in patients with type 2 diabetes

Aims/Introduction

Postprandial hyperglycemia is a potent risk factor for cardiovascular disease. Serum glycated albumin (GA) has been reported to reflect postprandial blood glucose fluctuations. In the present study, we assessed the possible correlation of GA with the presence of carotid plaque to evaluate the potential clinical usefulness of GA for predicting atherosclerotic cardiovascular complications in patients with type 2 diabetes.

Materials and Methods

Patients with type 2 diabetes (n = 236) admitted to Nippon Medical School Hospital (Tokyo, Japan) for glycemic control (aged 19–86 years, 81 females and 155 males) were examined. Clinical measurements were taken on admission. The presence of carotid plaque was assessed by ultrasonography.

Results

In patients with carotid plaque (n = 154), GA (P = 0.023) was higher than those without carotid plaque (n = 82). In contrast, neither fasting plasma glucose (P = 0.48) nor glycated hemoglobin (P = 0.41) was significantly different between the groups. The results of logistic regression analysis showed that GA (age‐ and sex‐adjusted odds ratio [95% confidence interval], 1.05 [1.01–1.09]; P = 0.017) and glycated hemoglobin (1.17 [1.01–1.37]; P = 0.036) were significantly associated with the presence of carotid plaque.

Conclusions

The positive correlation of serum GA with the presence of carotid plaque in type 2 diabetes suggests that GA will serve as a useful clinical marker for predicting diabetic cardiovascular complications.     

Liraglutide administration in type 2 diabetic patients who either received no previous treatment or were treated with an oral hypoglycemic agent showed greater efficacy than that in patients switching from insulin

Aims/Introduction

Liraglutide, a glucagon‐like peptide‐1 receptor agonist, is expected to provide a new treatment option for diabetes. However, the suitable timing of liraglutide administration in type 2 diabetic patients has not yet been clarified.

Materials and Methods

We reviewed type 2 diabetic patients (n = 155) who visited the Osaka Red Cross Hospital for glycemic control, with administration of liraglutide at a dose of 0.6 mg (average glycated hemoglobin [HbA_1c] level, 8.7 ± 0.1%). The effect of liraglutide based on the pretreatment status was compared. We also analyzed the background factors of both a successful and failed group of patients who switched to liraglutide from insulin.

Results

An improvement in blood glucose levels was confirmed in 122 of 155 patients. During the 4‐month observation period, the improvement in HbA_1c levels was significantly greater in the group of drug‐naïve/previous oral hypoglycemic agent (9.1 ± 0.2 to 7.2 ± 0.2%) than that in the group switching from insulin (8.6 ± 0.2 to 7.8 ± 0.2%). In addition, C‐peptide immunoreactivity levels (fasting > 2.2 ng/mL; delta >1.6 ng/mL; urine > 70 μg/day), younger age and a smaller number of insulin units used per day were considered important when deciding on switching to liraglutide from insulin.

Conclusions

Liraglutide was more effective in patients who had not been treated previously or received oral hypoglycemic agents than in patients switching from insulin. With respect to switching to liraglutide from insulin, the most important factors to be considered were C‐peptide immunoreactivity levels, age, and the number of insulin units used per day.     

Self‐perception of glycemic control among Japanese type 2 diabetic patients: accuracy of patient perception and characteristics of patients with misperception

Aims

Some diabetic patients, despite reporting a good perception of their glycemic control, actually show poor control and this misperception might well hinder successful diabetes management. This study aimed to assess patients'' self‐perception of glycemic control and to clarify factors associated with misperception of glycemic control status.

Methods

Baseline data from a hospital‐based prospective cohort of 519 type 2 diabetic patients were analyzed. Self‐perception of glycemic control and other items, including sociodemographic factors and blood test data, were determined from a self‐administered questionnaire and medical records. Factors associated with misperception were examined by age group (elderly [aged ≥ 65 years] vs non‐elderly [aged < 65 years]) using multiple logistic regression analysis.

Results

Among poorly controlled patients, misperception was higher in the elderly (glycated hemoglobin [HbA_1c] 7.4–8.3, 55.1%; HbA_1c >8.4, 44.8%) than in the non‐elderly (HbA_1c 7.4–8.3, 20.0%; HbA_1c >8.4, 18.9%). The factors significantly associated with misperception were as follows: high lifestyle regimen adherence in both age groups (non‐elderly group odds ratio [OR] 5.23; elderly group OR 5.15, respectively); high family support (OR = 7.32), failure to achieve blood pressure control (OR = 6.94) and having diabetic complications (OR = 0.06) among the non‐elderly; and long duration of diabetes (OR = 4.06) among the elderly.

Conclusions

For better management of diabetes, physicians should pay attention to the patient characteristics associated with misperception among uncontrolled diabetic patients, particularly among those who are elderly.     

Comparison of effects of pitavastatin and atorvastatin on glucose metabolism in type 2 diabetic patients with hypercholesterolemia

Aims/Introduction

The distinct effects of different statins on glycemic control have not been fully evaluated. In this open‐label, prospective, cross‐over clinical trial, we compared the effects of pitavastatin and atorvastatin on glycemic control in type 2 diabetic patients with hypercholesterolemia.

Materials and Methods

A total of 28 Japanese type 2 diabetics with hypercholesterolemia treated with rosuvastatin (2.5 mg/day) for at least 8 weeks were recruited to this quasi‐randomized cross‐over study. At study entry, the patients assigned to sequence 1 received pitavastatin (2 mg/day) for 12 weeks in period 1 and atorvastatin (10 mg/day) for another 12 weeks in period 2, whereas patients assigned to sequence 2 received atorvastatin (10 mg/day) for 12 weeks in period 1 and pitavastatin (2 mg/day) for another 12 weeks in period 2. Blood samples were collected at three visits (baseline, after 12 and 24 weeks).

Results

Lipid control was similar in both statins. The difference in glycated hemoglobin between pitavastatin and atorvastatin treatments was −0.18 (95% confidence interval −0.34 to −0.02; P = 0.03). Compared with atorvastatin, pitavastatin treatment significantly lowered the levels of glycoalbumin, fasting glucose and homeostasis model assessment of insulin resistance.

Conclusions

Our results showed that treatment with pitavastatin had a more favorable outcome on glycemic control in patients with type 2 diabetes compared with atorvastatin. This trial was registered with UMIN (no. 000003554).     

Hemoglobin A1c values are affected by hemoglobin level and gender in non‐anemic Koreans

Aims/Introduction

To evaluate whether hemoglobin A1c (HbA1c) levels are affected by hemoglobin level and gender.

Materials and Methods

A cross‐sectional analysis was carried out in a sample of 87,284 non‐diabetic Koreans without anemia who participated in comprehensive health check‐ups between January and December 2009 at the Kangbuk Samsung Hospital Total Healthcare Center in Seoul, Korea. We categorized men and women separately according to fasting plasma glucose and hemoglobin level to carry out the analysis.

Results

HbA1c increased steadily with increasing fasting plasma glucose level. Both men and women with lower hemoglobin had significantly higher HbA1c at a given fasting glucose level, and this result was consistent across the fasting glucose quintiles within the non‐diabetic range. Women had a lower mean hemoglobin value compared with men, and women had higher HbA1c levels at a given fasting glucose level consistently across the fasting glucose deciles. There was also a gender‐specific association between age and HbA1c (P < 0.001 for interaction).

Conclusions

HbA1c values were affected by hemoglobin level and gender in non‐anemic Koreans. Thus, hemoglobin level and gender should be considered in the diagnosis of diabetes using HbA1c.     

Randomized,placebo‐controlled,double‐blind glycemic control trial of novel sodium‐dependent glucose cotransporter 2 inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

In the present dose–response study, we evaluated the efficacy and safety of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium‐dependent glucose cotransporter 2, in Japanese patients with type 2 diabetes mellitus.

Materials and Methods

A total of 361 patients from 39 Japanese centers were randomized to receive either once‐daily oral ipragliflozin (12.5, 25, 50 or 100 mg) or a placebo for 12 weeks.

Results

All ipragliflozin‐treated groups had clinically significant, dose‐dependent decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose levels compared with placebo‐treated groups. The adjusted mean difference in HbA1c change from baseline to the end of treatment between the placebo and 12.5, 25, 50, and 100 mg ipragliflozin groups were −0.61%, −0.97%, −1.29%, and −1.31%, respectively (P < 0.001). Reductions in HbA1c levels were similar between obese and non‐obese patients, and were larger in patients with baseline HbA1c ≥8.4% than in those with HbA1c <8.4%. Furthermore, bodyweight significantly (P < 0.001) and dose‐dependently decreased among ipragliflozin‐treated groups compared with the placebo group. The incidence of adverse events was similar across all groups. However, mild increases in hematocrit and blood urea nitrogen were found in ipragliflozin treated groups.

Conclusions

Once‐daily administration of ipragliflozin was dose‐dependently effective in glycemic control without major adverse effects. Ipragliflozin was equally effective between obese and non‐obese patients, and led to weight loss in both groups. Ipragliflozin was safe and well‐tolerated in Japanese patients with type 2 diabetes mellitus. This trial was registered with ClinicalTrials.gov (no. NCT00621868).     

Safety of exenatide once weekly for 52 weeks in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

An initial 26‐week, randomized, open‐label study compared the efficacy and safety of exenatide 10 mcg twice daily with exenatide 2 mg once weekly in Asian patients with type 2 diabetes who experienced inadequate glycemic control with oral antidiabetes medications. The aim of this study was to evaluate the safety of exenatide once weekly in Japanese patients, a subset of the initial patient population, who continued into this extension study for an additional 26 weeks of therapy on exenatide once weekly, followed by 10 weeks without exenatide once weekly.

Materials and Methods

Japanese patients initially assigned to exenatide twice daily (n = 62) switched to exenatide once weekly for the extended 26 weeks, and patients initially assigned to exenatide once weekly (n = 74) continued on this regimen for the remainder of the study (total treatment of 52 weeks).

Results

A total of 68% of patients reported one or more treatment‐emergent adverse events during the extension period; the most common of these were nasopharyngitis (14%) and vomiting (6%). No major hypoglycemic episodes were reported. Improvements in glycated hemoglobin, fasting plasma glucose and postprandial glucose were maintained over 52 weeks of treatment. At week 52, bodyweight remained reduced from baseline.

Conclusions

Exenatide once weekly added to oral antidiabetes medication was well tolerated in Japanese patients with type 2 diabetes, and was associated with glycemic control and weight loss through to 52 weeks, supporting the use of exenatide once weekly as an adjunctive treatment for type 2 diabetes in this patient population. The initial 26‐week portion of this trial was registered with ClinicalTrials.gov (no. NCT00917267).