Basal-supported Oral Therapy Research Articles

Current State and Principles of Basal Insulin Therapy in Type 2 Diabetes.

Treatment with basal insulins is a fundamental part of management in many patients with type 2 diabetes mellitus. Multiple management schemes may be indicated in these individuals, for example, the use of oral antihyperglycemic agents with basal insulins (basal-supported oral therapy) or the combinations of basal insulins with glucagon-like peptide-1 receptor agonists; each of these strategies makes it easier to achieve glycemic control goals. A basic knowledge of the physiology, pharmacodynamic and pharmacokinetic aspects of the different basal insulins is essential to achieve treatment goals and compliance. This review addresses the principles of management with basal insulins.

DIVE/DPV registries: benefits and risks of analog insulin use in individuals 75 years and older with type 2 diabetes mellitus

IntroductionThe aims of this study were to characterize insulin-treated individuals aged ≥75 years with type 2 diabetes using basal insulin analogs (BIA) or regular insulins (human insulin (HI)/neutral protamine Hagedorn...

A Difference Between Bedtime and Pre-Breakfast Plasma Glucose Levels Indicates the Need for Prandial Insulin in Basal Insulin-Treated Type 2 Diabetic Patients with Normal Fasting Glucose.

AimIn the present analysis, we characterised the efficacy and safety of adding a single daily injection of insulin glulisine to optimised basal-supported oral therapy (BOT) in patients with a high BeAM value, defined as a more than 50 mg/dl difference between bedtime and pre-breakfast blood glucose.MethodsThe BeAM value was retrospectively calculated for patients pooled from two clinical trials that supplemented BOT with glulisine. Data regarding changes in HbA1c, fasting plasma glucose (FPG), and postprandial glucose (PPG) levels from observation periods of 3 to 6 months were assessed.ResultsOut of 358 patients that received BOT/glulisine, 182 had a high BeAM value. Patients with a high BeAM value were older and had a longer diabetes duration than patients with a medium BeAM value. Significant reductions in HbA1c (7.5% to 7.2% [59 to 55 mmol/mol], p<0.0001) and PPG (202 to 143 mg/dl, p<0.0001) levels were documented. The proportion of patients with a high BeAM value achieving an HbA1c <7% [53 mmol/mol], alone or in combination with no hypoglycaemia, was lower than that of patients with a medium BeAM value.ConclusionThe analysis indicates that the supplementation of BOT with a single daily injection of prandial insulin is safe and effective for reducing HbA1c and PPG levels in patients with a high BeAM value (more than 50 mg/dl). However, patients with a medium BeAM value also responded well, which suggests that they should also be considered candidates for this change in therapy.

HbA1c target achievement in the elderly: results of the Titration and Optimization trial for initiation of insulin glargine 100 U/mL in patients with type 2 diabetes poorly controlled on oral antidiabetic drugs

ObjectivesTo identify real-world, age-related trends in the use of insulin glargine 100 U/mL (Gla-100) as part of basal-supported oral therapy (BOT).Research design and methodsThe prospective, observational Titration and Optimization registry...

Predictors of treatment response in type-2 diabetes patients initiating basal-supported oral therapy with insulin glargine 100 U/mL: A sub-analysis of the Titration and OPtimisation (TOP) registry.

The aim of this study was to identify predictors of long-term response to the initiation of basal-supported oral therapy (BOT) with insulin glargine (IGlar-100). Patients from the observational TOP registry were grouped based on those who had achieved (responders) and those who had not achieved (non-responders) their HBA1c target and/or FBG ≤110 mg/dL 12 months after IGlar-100 initiation. Independent predictors of treatment response were identified by regression analysis. Data for 2444 patients were analysed (responders, n = 1610; non-responders, n = 834). Although the IGlar-100 dose increase over 12 months was larger for non-responders (+12.83 vs +9.46 U/d; P < 0.0001), the corresponding decrease in HbA1c was smaller (-0.88% vs -1.57%). Independent predictors of response included lower BMI (OR, 0.97; 95% CI, 0.95-1.00), lower FBG (OR, 0.98; 95% CI, 0.97-0.98) and HbA1c values at baseline (OR, 0.24; 95% CI, 0.18-0.31), a less ambitious HbA1c target (OR, 5.07; 95% CI, 3.37-7.63) and bedtime administration of IGlar-100 (OR, 1.55; 95% CI, 1.12-2.14). In conclusion, HbA1c was the clinically most significant baseline characteristic predictive of response to BOT. This may suggest an advantage of IGlar-100 initiation prior to excessive hyperglycaemia escalation.

Effect of the Combination Therapy of Liraglutide, a GLP-1 Receptor Analog, and IDegAsp in Patients with Type 2 Diabetes

Background: Diabetes care management aims to not only achieve good glycemic control but also maintain the quality of life (QoL). Basal insulin-treated patients frequently receive bolus insulin as a strengthening therapy; however, concerns exist about QoL due to the increasing number of injections. We examined the glycemic effect and QoL in patients treated with liraglutide (Lira) and insulin degludec/insulin aspart (IDegAsp). Methods: Patients with type 2 diabetes treated with basal-supported oral therapy (BOT) and DPP-4 inhibitor were enrolled in this observational study. Basal insulin was switched to IDegAsp at the same dose and DPP-4 inhibitor to Lira simultaneously; no titration protocol was used. We estimated the clinical and laboratory parameters and assessed the change in QoL within 12 weeks using the diabetes therapy-related QoL (DTR-QoL) questionnaire. The timing of dose up in regard to IDegAsp and Lira was also determined. Results: Fourteen patients were enrolled (male/female: 9/5, age (years): 63.6). The IDegAsp dose ranged from 9.1 to 13.7 U; all patients received 0.9 mg/day of Lira. The combination therapy significantly decreased HbA1c levels (8.7% vs. 7.1%, P=0.02), pre-breakfast glucose level (138.2 mg/dL vs. 108.9 mg/dL, P=0.044), bodyweight (62.9 kg vs. 60.3 kg, P=0.003), and BMI (24.6 vs. 23.5, P=0.004). The total DTR-QoL score at baseline was 61.6 and significantly improved to 73.2 (P=0.004). Significant improvement was also seen in D3 score (hypoglycemia; 63.6 vs. 81.4, P=0.036). D4 score (satisfaction with treatment) showed an increasing trend (59.0 vs. 78.2) and was negatively correlated with HbA1c levels (P=0.049). Conclusion: The change from BOT to the combination therapy of Lira and IDegAsp significantly improved glycemic control and reduced the bodyweight without deteriorating QoL in type 2 diabetes, although the treatment modality changed from one-injection to two-injection therapy. Disclosure M. Harada: None. M. Shinoda: None. R. Sakamoto: None. J. Suzuki: None. K. Takahashi: None. T. Yamakawa: None.

Efficacy and Safety of Basal-Supported Prandial GLP-1 Receptor Agonist Therapy

Aim: To assess the safety and efficacy of basal-supported prandial GLP-1 receptor agonist therapy (BPT)* in type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM, who had previously received insulin injection therapy and who had had their treatment switched to BPT (liraglutide), were retrospectively recruited. The efficacy of BPT was assessed by determining changes in HbA1c, body weight and total daily insulin dose from baseline to 4 months after BPT initiation. Safety was assessed by comparing the frequency of hypoglycemic episodes at baseline and after 4 months. The Wilcoxon test was used to analyze changes in parameters throughout the study period. Results: Twenty-nine patients, previously treated with basal-supported oral therapy (BOT), basal-bolus insulin, or pre-mixed insulin, were recruited. When analyzed together, there was no change in HbA1c throughout the study period, but body weight decreased (baseline 68.8 ± 13.2 kg vs. month 4 67.3 ± 13.1 kg; p

Fracture risk in patients with type 2 diabetes under different antidiabetic treatment regimens: a retrospective database analysis in primary care

AimType 2 diabetes is associated with an increased risk of fractures. There are a few studies on the effects of diabetes treatment on fracture risk. The aim was to investigate the fracture risk related to various types of insulin therapy in primary care practices.MethodsData from 105,960 type 2 diabetes patients from 1,072 general and internal medicine practices in Germany were retrospectively analyzed (Disease Analyzer database; 01/2000–12/2013). Fracture risk of the following therapies was compared using multivariate logistic regression models adjusting for age, sex, diabetes care, comorbidity, and glycemic control (HbAlc): 1) incident insulin therapy versus oral antidiabetic drugs, 2) basal-supported oral therapy versus supplementary insulin therapy versus conventional insulin therapy, and 3) insulin glargine versus insulin detemir versus NPH insulin.ResultsThere was a lower odds of having incident fractures in the oral antidiabetic drug group compared to incident insulin users, although not significant (odds ratio [OR]; 95% confidence interval: 0.87; 0.72–1.06). There were increased odds for conventional insulin therapy (OR: 1.59; 95% CI [confidence interval] 0.89–2.84) and supplementary insulin therapy (OR: 1.20; 0.63–2.27) compared to basal-supported oral therapy, which was not significant as well. Overall, there was no significant difference in fracture risk for basal insulins (glargine, detemir, NPH insulin). After a treatment duration ≥2 years, insulin glargine showed a lower odds of having ≥1 fracture compared to NPH users (OR: 0.78; 0.65–0.95) (detemir vs NPH insulin: OR: 1.03; 0.79–1.36).ConclusionLong-standing therapy with insulin glargine was associated with a lower odds of having any fractures compared to NPH insulin. Further studies are required to investigate whether the lower chance is due to a reduced frequency of hypoglycemia.

Efficacy and safety assessment of basal supported oral therapy (BOT) with insulin glargine in a real-life clinical setting, stratified by concomitant orally administered antidiabetic agent (OAD) regimens including dipeptidyl peptidase-4 inhibitor (DPP-4i): subanalysis of the ALOHA2 study, drug-use surveillance in Japan.

We aimed to explore concomitant orally administered antidiabetic agent (OAD) regimens used in basal supported oral therapy (BOT) with insulin glargine in a real-life setting, and to assess the efficacy and safety of each regimen using data from the Add-on Lantus® to Oral Hypoglycemic Agents 2 study, a 24-week observational study in Japanese type 2 diabetes patients. Among 1629 insulin-naïve patients who had a glycosylated hemoglobin (HbA1c) value of ≥6.5% during the previous 4weeks and were treated with BOT during the observational period, 1227 patients who retained the same concomitant OAD regimens throughout the period were included in the analysis. Sulfonylurea (71.5%), dipeptidyl peptidase-4 inhibitor (DPP-4i; 60.7%), and biguanide (BG; 48.6%) were commonly administered OADs in BOT. The HbA1c level decreased in patients taking BG alone (-2.76%) and DPP-4i alone (-2.46%). Of the three OADs, mean doses of the most frequently administered OAD changed from baseline to the final evaluation point: 2.5-2.3mg for glimepiride, 59.1-58.7mg for sitagliptin, and 1145.6-1168.2mg for metformin. No significant difference in the hypoglycemia incidence rate was found between regimens (p=0.3765), with incidence rates of 1.9% (DPP-4i alone) to 7.0% (other regimens) observed. DPP-4i plays a major role in BOT with insulin glargine in a real-life setting. The incidence of hypoglycemia did not differ significantly between BOT regimens, including DPP-4i. Insulin glargine added to DPP-4i is a potential therapeutic approach.

Status of basal-supported oral therapy in Chinese type 2 diabetic patients with inadequate glycemic control on oral anti-diabetic drugs.

Timely initiation and titration of basal insulin added on to oral anti-diabetic drugs contribute to better glycemic control. However, implementation of basal-supported oral therapy in China is not yet clear. This nationwide, prospective, 12-week observational study was designed to explore the current status of basal-supported oral therapy in patients with type 2 diabetes in China. Type 2 diabetic patients with inadequate glycemic control on anti-diabetic drugs who were to start basal-supported oral therapy with insulin glargine at outpatient clinics were enrolled from 134 hospitals in China. Both the decision to initiate basal insulin and insulin dose adjustment were at the physician's discretion. Fasting plasma glucose (FPG) and haemoglobin A1c were measured, and the starting dose of insulin were recorded at baseline. Self-monitored fasting capillary blood glucose and the adjusting dose of insulin were collected during the study. A total of 11,192 out of 13,259 enrolled patients finished the 12-week study. FPG and haemoglobin A1c at basal-supported oral therapy initiation were 11.2 mmol/L and 9.4%, respectively, with insulin glargine started at 0.190 IU/kg/day. Insulin dose was increased 1.8 IU in average within 12 weeks. Fifty-nine percent of the patients achieved fasting capillary blood glucose ≤ 7.0 mmol/L. More patients achieved the glucose target in the group with lower baseline FPG level. Notable geographical differences of physicians' treatment habits in the current management of basal-supported oral therapy were also observed. A great gap between everyday clinical practice and guidelines exists in China, reflected by the delayed initiation, slow dose titration and geographical differences of basal-supported oral therapy management. A concrete guideline of basal-supported oral therapy management is needed in the clinical application.

Treatment intensification using long-acting insulin -predictors of future basal insulin supported oral therapy in the DIVE registry.

BackgroundIn patients with type-2 diabetes receiving oral antidiabetic drugs (OADs), the addition of insulin is frequently required to achieve sufficient control over blood glucose levels. It is, however, difficult to predict if, when and in which patients insulin therapy will be needed. We aimed to identify patient related variables associated with the addition of basal insulin to oral therapy resulting in a basal supported oral therapy (BOT).MethodsDIVE (DIabetes Versorgungs-Evaluation) is a prospective, observational, multi-centre diabetes registry established in Germany in 2011. For the present explorative analysis, 31,008 patients with type-2 diabetes prescribed at least one OAD were included. Patients who had previously received insulin and those over 90 years old were excluded. The event of interest was defined as the initiation of BOT during the observational period. Cause-specific Cox proportional hazards models based on a competing risk framework were applied for risk quantification.ResultsMultivariable adjusted hazard ratios demonstrated that longer diabetes duration, higher BMI, poorer glycaemic control, documentation of any micro- or macrovascular comorbidity, the presence of concomitant non-antidiabetic pharmacotherapies, and greater numbers of prescribed OADs increased the likelihood of BOT initiation. On the other hand BOT initiation was less likely in patients with older age and female gender. Analysing the likelihood of OAD termination without initiation of BOT provided supportive evidence for the variables predictive of BOT initiation.DiscussionAnalysis of the DIVE registry has resulted in the identification of a number of factors that may be predictive for the initiation of BOT for type-2 diabetes patients initially prescribed one or more OADs. Poor glycaemic control, the presence of vascular comorbidities and concomitant medications, and a greater number of OADs were all detected to increase the risk of a switch to BOT. Female gender and younger age showed protective properties.ConclusionsThe close monitoring of patients displaying these characteristics may help to identify individuals who might benefit from early addition of insulin therapy to their oral treatment regimen.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-015-0051-0) contains supplementary material, which is available to authorized users.

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.

Effect of switching basal insulin regimen to degludec on quality of life in Japanese patients with type 1 and type 2 diabetes mellitus.

BackgroundMaintainance of a stable basal insulin level is important for glycemic control in treatment of diabetes mellitus. Recently introduced insulin degludec has the longest duration of action among basal insulin formulations. The purpose of this study was to assess changes in quality of life (QOL) associated with switching the basal insulin regimen to degludec in patients with type 1 and type 2 diabetes mellitus.MethodsThis 24-week open-label intervention study included type 1 (n = 10) and type 2 (n = 20) diabetes mellitus patients, with adequately controlled hemoglobin A1c (HbA1c), who had received insulin glargine or detemir for at least 6 months. The primary outcome was change of QOL from baseline, as assessed by the Diabetes Therapy-Related QOL (DTR-QOL) application, after switching from glargine or detemir to degludec. HbA1c and other parameters were also assessed as secondary outcomes.ResultsQOL and HbA1c in patients with type 1 diabetes mellitus were unchanged during this study. In patients with type 2 diabetes mellitus, HbA1c did not change, but total DTR-QOL score was significantly improved from baseline after switching to degludec. The DTR-QOL Factor 2, “Anxiety and dissatisfaction with treatment”, was significantly improved in patients with type 2 diabetes mellitus and especially in the subgroup receiving basal supported oral therapy (BOT).ConclusionsSwitching of the basal insulin regimen from glargine or detemir to degludec significantly improved the QOL of patients with type 2 diabetes mellitus who were receiving BOT, by reducing mental stress or anxiety about their treatment.

Improved Treatment Satisfaction and Self-reported Health Status after Introduction of Basal-Supported Oral Therapy Using Insulin Glargine in Patients with Type 2 Diabetes: Sub-Analysis of ALOHA2 Study.

IntroductionThis study aimed to assess treatment satisfaction and self-reported health status in insulin-naïve patients with type 2 diabetes mellitus (T2DM) who started insulin glargine basal-supported oral therapy (BOT) with glycated hemoglobin (HbA1c) value of ≥6.5%, using data from Add-on Lantus® to Oral Hypoglycemic Agents 2 (ALOHA2) study, a 24-week single-arm, observational study of Japanese patients with T2DM, conducted as drug use surveillance in Japan.MethodsTreatment satisfaction was measured using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and change version (DTSQc) and self-reported health status using EuroQol 5 Dimension (EQ-5D). The results were compared between the groups stratified by HbA1c level at the final evaluation point: target-achieved (<7.0%) and target-not-achieved groups (≥7.0%).ResultsIn 1251 patients (336 in the target-achieved group), scores of DTSQs, DTSQc, and EQ-5D indicated significant improvement from baseline to the final evaluation point (both P < 0.01). The mean change in DTSQs scale score, DTSQs item score, and EQ-5D index score, and mean DTSQc scale score were significantly improved in the target-achieved group compared with the target-not-achieved group (P < 0.05 for all). DTSQs scale score and HbA1c level showed the same pattern of chronological change. Data analysis in patients stratified by DTSQs score showed better glycemic control in the high satisfaction group.ConclusionFollowing insulin glargine BOT introduction, treatment satisfaction and health status were improved from patients’ perspectives despite the need for daily injections. Based on the possible association between HbA1c 7.0% level achievement, treatment satisfaction, and health status, better glycemic control may be a key to successful treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-015-0111-5) contains supplementary material, which is available to authorized users.

Importance of Geriatric Syndromes in Older Patients with Diabetes with de novo Insulin Treatment: The VEGAS Study.

AimsThe VEGAS study was conducted to evaluate representative data of de novo insulin-treated older patients with type 2 diabetes in the outpatient setting in Germany.MethodsIn this prospective, multicenter, non-interventional observational study, a nationwide written survey was carried out among practitioners (02/2011–06/2011). Older patients, aged ≥70 years, starting de novo insulin therapy, were documented.ResultsData from 4,858 patients from about 500 centers (mean age: 78.2 ± 5.4 years; mean glycosylated hemoglobin [HbA1c]: 70 ± 14.2 mmol/mol [8.6 ± 1.3 %]) were collected. The mean target HbA1c value was 55 ± 6.6 mmol/mol (7.2 ± 0.6 %). 91.1 % of geriatric patients were multi-morbid. 96.2 % showed at least one physical or psychological geriatric syndrome. Most of the patients were notably impaired according to their age. Conventional insulin therapy and basal-supported oral therapy were the most frequently planned treatment regimens (39.1 and 31.1 %). Important factors in the selection of the insulin treatment regimen were an efficient HbA1c decrease (65.6 %), easy administration (55.7 %), and also a patient’s ability to self-administer insulin (38.5 %). De novo insulin treatment increased care requirements (22.7 %). 22.3 % of the relatives were scheduled to receive special training. Specific training programs for older patients with diabetes were planned in only 7.3 % of cases.ConclusionsThe data demonstrate the high prevalence of geriatric syndromes during de novo insulin treatment. Individual therapeutic goals and regimes are based on practicability, in particular, the receipt of autonomy and the care requirement. Diabetes education with adapted programs is currently under-represented. Important factors for the choice of an insulin treatment regimen were an efficient HbA1c decrease, easy administration, and a patient’s ability for self-administration.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-015-0014-9) contains supplementary material, which is available to authorized users.

Treatment persistence after initiating basal insulin in type 2 diabetes patients: A primary care database analysis

AimsTo compare persistence and its predictors in type 2 diabetes patients in primary care, initiating either basal supported oral therapy (BOT) or intensified conventional therapy (ICT) with glargine, detemir, or NPH insulin. MethodsIn the BOT cohort, 1398 glargine (mean age: 68 years), 292 detemir (66 years), and 874 NPH (65 years) users from 918 practices were retrospectively analyzed (Disease Analyzer, Germany: 2008–2012). The ICT group incorporated 866 glargine (64 years), 512 detemir (60 years), and 1794 NPH (64 years) new users. Persistence was defined as proportion of patients remaining on the initial basal insulin (glargine, detemir and NPH insulin) over 2 years. Persistence was evaluated by Kaplan–Meier curves (log-rank tests) and Cox regression adjusting for age, sex, diabetes duration, antidiabetic co-therapy, comorbidities, specialist care, and private health insurance. ResultsIn BOT, two-year persistence was 65%, 53%, and 59% in glargine, detemir, and NPH users, respectively (p<0.001). In ICT, persistence was higher without differences between groups: 84%, 85%, 86% in glargine, detemir, and NPH, respectively (p=0.536). In BOT, detemir and NPH users were more likely to discontinue basal insulin compared with glargine (detemir vs. glargine: adjusted Hazard Ratio; 95% CI: 1.56; 1.31–1.87; NPH vs. glargine: 1.22; 1.07–1.38). Heart failure (1.39; 1.16–1.67) was another predictor of non-persistence, whereas higher age (per year: 0.99; 0.98–0.99), metformin (0.61; 0.54–0.69), and sulfonylurea co-medication (0.86; 0.77–0.97) were associated with lower discontinuation. ConclusionsIn BOT, treatment persistence among type 2 diabetes patients initiating basal insulin is influenced by type of insulin, antidiabetic co-medication, and patient characteristics.

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.

強化療法からSGLT2阻害剤を用いたBOTに切り替え可能であった肥満2型糖尿病患者2症例

強化療法からSGLT2阻害剤を用いたBOTに切り替え可能であった肥満2型糖尿病患者2症例

Effectiveness and safety of basal supported oral therapy with insulin glargine, in Japanese insulin-naive, type 2 diabetes patients, with or without microvascular complications: subanalysis of the observational, non-interventional, 24-week follow-up Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA) study

AimsThe aim of this study is to evaluate effectiveness and safety of basal supported oral therapy (BOT) using insulin glargine in insulin-naive Japanese patients, with and without microvascular complications. MethodsThis sub-group analysis of observational, non-interventional ALOHA study, assessed changes in glycemic parameters and glargine dose, at 24weeks or at glargine discontinuation. Count of hypoglycemic episodes was based on physicians' documentation of patient reports. Patients were stratified according to presence/absence of microvascular complications, at baseline. Relationships between baseline patient characteristics and achievement of HbA1c <7% were examined by multivariate regression analysis. ResultsA total of 3631 patients, included during 2007–2009, were stratified in sub-groups: no complications (n= 1889), retinopathy (n=318), neuropathy (n=297), nephropathy (n=356), retinopathy+neuropathy (n= 174), retinopathy+nephropathy (n=154), neuropathy+nephropathy (n=142), and retinopathy+neuropathy+nephropathy (n=301). Changes in HbA1c, fasting and postprandial plasma glucose, and glargine daily dose were similar among patients with and without complications. Response-rate for achieving HbA1c <7.0% was highest in patients without complications (19.1%). In multivariate analysis, patients without complications showed significantly higher odds of attaining HbA1c <7%, independent of diabetes duration and baseline HbA1c levels. Patients with retinopathy+nephropathy had the lowest response-rate (8.8%) and highest hypoglycemic-rate (3.2%). ConclusionJapanese insulin-naive patients without complications, on BOT with glargine, show higher chances of attaining HbA1c <7.0% than those with complications.

Efficacy of adding once-daily insulin glulisine in Japanese type 2 diabetes patients treated with insulin glargine and sitagliptin.

Glucose fluctuation often remains to be corrected under basal-supported oral therapy. We investigated the efficacy of adding once-daily rapid-acting insulin in Japanese diabetes patients treated with basal-supported oral therapy. In this 8-week, parallel-group, randomized, open-label trial, 62 Japanese adults with type 2 diabetes treated with insulin glargine and 50 mg of sitagliptin were randomized into the following two arms: the single-bolus group, in which once-daily insulin glulisine was initiated at a main meal at a fifth (i.e., 20%) the dose of insulin glargine, and the control group, in which the dose of sitagliptin was maximized to 100 mg. The primary end point was the change of glycemic fluctuation assessed with the M-value. Baseline hemoglobin A1c levels, mean blood glucose profiles, and M-value were 7.2 ± 0.6%, 9.3 ± 1.7 mmol/L, and 21 ± 13 units, respectively. At the end of the study, the single-bolus group had a greater reduction of M-value than the control group (P=0.02); the difference was 6.5 units (95% confidence interval, 1.1-11.9 units). The single-bolus group also had a greater reduction of mean blood glucose levels (P=0.01). There were no significant differences in the incidence of hypoglycemia or the weight change between the two groups (P>0.05). Adding once-daily insulin glulisine was more effective in controlling the glycemic fluctuation in Japanese type 2 diabetes patients treated with insulin glargine together with sitagliptin.