On Oral Antidiabetic Drugs Research Articles

Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program.

IntroductionThe efficacy and safety of insulin degludec/liraglutide (IDegLira) has been evaluated in the Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase 3 clinical trial program. In this post hoc analysis, we compared the efficacy and safety of IDegLira in the Indian subpopulation with the results from the global trial population of DUAL trials. The analysis includes participants uncontrolled on oral antidiabetic drugs (OADs) in DUAL I and DUAL IV and participants uncontrolled on basal insulin and OADs in DUAL II.MethodsThree phase 3 trials were included in the analysis: DUAL I extension (IDegLira vs. insulin degludec or liraglutide 1.8 mg in participants uncontrolled on metformin ± pioglitazone; 52 weeks; n = 1663), DUAL IV (IDegLira vs. placebo as an add-on to a regimen of sulfonylurea ± metformin; 26 weeks; n = 435) and DUAL II (IDegLira vs. insulin degludec in participants uncontrolled on basal insulin + OADs; 26 weeks; n = 398). There were 251, 64 and 64 participants, respectively, at the Indian sites.ResultsIn the Indian subpopulations, the reductions in glycated hemoglobin (HbA1c) with IDegLira were substantial [DUAL I: 1.96% (−21 mmol/mol); DUAL IV: −1.40% (−15 mmol/mol); DUAL II: −2.20% (−24 mmol/mol)] and significantly greater than those in the comparators in each trial. IDegLira was generally weight-neutral after the administration of OADs (−0.3 and +0.6 kg in DUAL I and DUAL IV) and resulted in weight loss after the administration of basal insulin (−2.1 kg in DUAL II). Hypoglycemia rates were 1.98, 1.08 and 0.37 events/patient-years of exposure (PYE) for IDegLira, insulin degludec and liraglutide in DUAL I, 4.06 and 0.36 events/PYE for IDegLira and placebo in DUAL IV and 1.16 and 0.83 events/PYE with IDegLira and insulin degludec in DUAL II.ConclusionsResults from the Indian subpopulations reflect those of the global study populations, supporting IDegLira as an effective and safe treatment option for people with type 2 diabetes inadequately controlled on OADs or basal insulin + OADs in the South Asian population.Trial RegistrationClinicalTrials.gov identifier, NCT01336023 (DUAL I), NCT01392573 (DUAL II), NCT01618162 (DUAL IV).FundingNovo Nordisk A/S, Bagsvaerd, Denmark.

Insulin Detemir in Combination with Oral Antidiabetic Drugs Improves Glycemic Control in Persons with Type 2 Diabetes in Near East Countries: Results from the Lebanese Subgroup.

To evaluate the effectiveness and safety of insulin detemir treatment as add-on therapy in a real-world setting of Lebanese insulin naïve persons, with type 2 diabetes poorly controlled on oral antidiabetic drugs (OADs). Our study was a prospective, observational study representing the Lebanese arm of the multinational prospective and observational study involving 2,155 persons across Near East countries, Lebanon, Pakistan, Israel and Jordan. Effectiveness endpoints were changes in HbA1c, fasting and post-prandial glucose (FPG, PPG) after 24 weeks of treatment with insulin detemir in eligible persons. Safety endpoints were number of hypoglycemic events, incidence of adverse drug reactions (ADRs), serious ADRs, adverse events, and body weight change between baseline and end of treatment. 868 persons were included (mean age: 59.5 ± 10.4 years, men: 55.3%). Glycemic control improved with significant reduction in mean HbA1c from 9.7 ± 1.6% to 7.2 ± 1% (P<.0001). The percentage of persons who achieved the target of HbA1c<7% increased from .7% at baseline to 39% at week 24. Mean FPG decreased significantly from 213.7 ± 60.1 mg/dL to 120.3 ± 25.7 mg/dL (P<.001), and mean PPG from 271 ± 65.3 mg/dL to 158.1 ± 36.4 mg/dL (P<.0001). The rate of major hypoglycemic episodes decreased from .1498 at baseline to .0448 at week 24. Three adverse events but no ADR or serious ADR were reported. Body weight decreased from 80.4±13.2 Kg to 79.9±12.5 Kg (P<.0001). Initiating insulin detemir in a clinical health care setting among Lebanese with type 2 diabetes mellitus on OADs improves glycemic control with no increase in hypoglycemia, adverse events or weight compared with baseline.

Exploring the characteristics of suboptimally controlled patients after 24weeks of basal insulin treatment: An individualized approach to intensification.

To identify characteristics of suboptimally controlled patients with type 2 diabetes (T2DM) on basal insulin treatment who may benefit from intensive titration or further intensification of treatment. A post hoc analysis of SOLVE: a 24-week, international, observational study conducted in 17,374 patients with T2DM inadequately controlled on oral antidiabetic drugs (OADs) started on once-daily insulin detemir. Patients were divided into two groups based on whether they achieved HbA1c<7.0% (<53.0mmol/mol) or not at final visit. Suboptimal glycemic control (HbA1c⩾7.0 [⩾53.0mmol/mol]) was independently associated with several baseline characteristics including higher baseline HbA1c (odds ratio [95% confidence interval]: 1.56 [1.50;1.62]; p<0.0001) and body mass index (BMI) (1.03 [1.02;1.04]; p<0.0001), longer duration of diabetes (5-10years: 1.44 [1.25;1.66]; >10years: 1.44 [1.17;1.77]; p<0.0001), and greater number of OADs (two OADs: 1.27 [1.12;1.44]; >2 OADs: 1.38 [1.14;1.66]; p=0.0003). Overall reporting of hypoglycemia was low; fewer patients with HbA1c⩾7.0% (⩾53.0mmol/mol) reported hypoglycemic events compared with patients with HbA1c<7.0% (9.8% vs. 12.5%, respectively; p<0.001). Baseline characteristics related to severity of disease were strongly associated with suboptimal glycemic control in patients with T2DM receiving basal insulin. These factors may help clinicians in identifying patients who may require an individualized approach to titration or intensification of treatment. NCT00740519.

Effects of metformin treatment on blood leptin and ghrelin levels in patients with type 2 diabetes mellitus.

The aim of the present study was to conduct a meta-analysis of randomized controlled trials (RCTs) that investigated the effects of metformin on blood leptin and ghrelin levels in patients with type 2 diabetes mellitus (T2DM). Literature searches were performed using MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov, and RCTs that investigated the effects of metformin on blood leptin and ghrelin levels in patients with T2DM were selected. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated. Twelve RCTs met the eligibility criteria and were included in the meta-analysis. There was no significant difference in blood leptin between the metformin and control groups (SMD 0.03; 95% CI -0.35%, 0.42 %; P = 0.86), although there was a significant difference in blood leptin levels between the metformin group and the group on oral antidiabetic drugs (OADs) other than metformin (SMD -0.39; 95% CI -0.76%, -0.01 %; P = 0.04). There were no significant differences in blood ghrelin levels. Metformin treatment was not associated with a decrease in blood leptin levels in patients with T2DM compared with levels in patients in the control group. Moreover, metformin treatment was not associated with increases in blood ghrelin levels compared with the control and other OADs groups. However, blood leptin levels were significantly lower in the metformin compared with the other OADs group.

Benefits of combination of insulin degludec and liraglutide are independent of baseline glycated haemoglobin level and duration of type 2 diabetes.

AimTo evaluate, using post hoc analyses, whether the novel combination of a basal insulin, insulin degludec, and a glucagon‐like peptide‐1 receptor agonist, liraglutide (IDegLira), was consistently effective in patients with type 2 diabetes (T2D), regardless of the stage of T2D progression.MethodsUsing data from the DUAL I extension [insulin‐naïve patients uncontrolled on oral antidiabetic drugs (OADs), n = 1660, 52 weeks] and DUAL II (patients uncontrolled on basal insulin plus OADs, n = 398, 26 weeks) randomized trials, the efficacy of IDegLira was investigated with regard to measures of disease progression stage including baseline glycated haemoglobin (HbA1c), disease duration and previous insulin dose.ResultsAcross four categories of baseline HbA1c (≤7.5–9.0%), HbA1c reductions were significantly greater with IDegLira (1.1–2.5%) compared with IDeg or liraglutide alone in DUAL I. In DUAL II, HbA1c reductions were significantly greater with IDegLira (0.9–2.5%) than with IDeg in all but the lowest HbA1c category. In DUAL I, insulin dose and hypoglycaemia rate were lower across all baseline HbA1c categories for IDegLira versus IDeg, while hypoglycaemia was higher with IDegLira than liraglutide, irrespective of baseline HbA1c. In DUAL II, insulin dose and hypoglycaemia rate were similar with IDegLira and IDeg (maximum dose limited to 50 U) independent of baseline HbA1c. The reduction in HbA1c with IDegLira was independent of disease duration and previous insulin dose but varied depending on pre‐trial OAD treatment.Conclusions IDegLira effectively lowered HbA1c across a range of measures, implying suitability for patients with either early or advanced T2D.

Quality of Life of Insulin-Naïve People with Type 2 Diabetes Mellitus Inadequately Controlled on Oral Antidiabetic Drugs after the Addition of Insulin Glargine, in Every Day Clinical Practice in Greece

Objectives: To assess the quality of life (QoL) of insulin-naive people with Type 2 Mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs)) after the addition of insulin glargine through the use of self-reported questionnaires (ADDQoL, DTSQs and DTSQc). Design: Insulin-naive Greek patients with T2DM >1 year inadequately controlled on at least 2 OADs as assessed by HbA1c between 7.0%-9.0% were recruited. The addition of insulin glargine to the treatment was initiated within one month prior to enrollment and patients were evaluated at the beginning of the study and at 3 and 6 months through HbA1c measurements and self-reported quality of life questionnaires. Data were analyzed using descriptive statistics. Results: HbA1c (%) ± SD decreased from 8.3±0.5 to 7.4±0.7 and 7.2±0.6 at 3 and 6 months, respectively (p<0.001). No significant changes in symptomatic hypoglycemia and no severe hypoglycemia were reported. Concerning the ADDQoL-19, the present QoL score improved from 0.42± 0.97 to 0.79±0.81 and 0.93± 0.82 (p<0.001), the If no Diabetes QoL score decreased from -1.50± 0.78 to -1.51±0.78 and increased to -1.42± 0.80 (p=0.03) and the Average Weighted Impact-AWI score improved from -2.48± 1.83 to -2.46± 1.67 and -2.35± 1.71 at 3 and 6 months, respectively (p=0.03). The DTSQS score improved from 22.58±7.13 to 26.34±6.51 and 27.10±6.86 (p<0.001) while perceived frequency of hypo/ hyperglycaemia decreased from 5.22±1.89 to 3.82±2.11 and 3.20±2.12 at 3 and 6 months, respectively (p<0.001). The DTSQC score at 6 months was 11.45±6.70 (p<0.001), while the respective hypo/hyperglycaemia score was -2.74±2.73 (p<0.001). Conclusion: The improved glycaemic control as assessed by HbA1c values, achieved by the addition of insulin glargine to the treatment of patients with T2DM inadequately controlled with OADs resulted in a positive impact on QoL and treatment satisfaction (TS) with reduced perception of hypo/hyperglycaemia.

Insulin vs. GLP-1 Receptor Agonist as First Injectable Therapy in Primary Care

Patients with type 2 diabetes mellitus (T2DM) uncontrolled on oral anti-diabetic drugs (OADs) often progress to an injectable therapy with insulin (INS) or a GLP-1 receptor agonist (GLP-1 RA). Better understanding of patient and provider characteristics and reasons behind initiation of INS or a GLP-1 RA may inform their most appropriate use in T2DM management.

Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India 2011 Study

Objectives:DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to investigate the relationship between diabetes control, management and complications in a subset of urban Indian diabetes patients treated at referral diabetes care centres in India.Materials and Methods:This was a cross-sectional, multicentre (330 centres) survey in 6168 diabetes patients treated at general hospitals, diabetes clinics and referral clinics across India. Patient data, including medical and clinical examination reports during the past year were collected during their routine visit. The patients’ and physicians’ perceptions about diabetes management were recorded using a questionnaire.Results:A total of 6168 subjects with diabetes (95.8% type 2), mean age 51.9 ± 12.4 years and mean duration of diabetes, 6.9 ± 6.4 years were included. Mean HbA1c was 8.9 ± 2.1% and the mean fasting (FPG), post prandial (PPG) and random (RBG) plasma glucose levels were 148 ± 50 mg/dl 205 ± 66 mg/dl and 193 ± 68mg/dl respectively. Neuropathy was the most common complication (41.4%); other complications were: Foot (32.7%), eye (19.7%), cardiovascular (6.8%) and nephropathy (6.2%). The number of diabetic complications increased with mean duration of diabetes. Most (93.2%) of the patients were on oral anti-diabetic drugs (OADs) and 35.2% were on insulin (±OADs). More than 15% physicians felt that the greatest barrier to insulin therapy from patient's perspective were pain and fear of using injectable modality; 5.2% felt that the greatest barrier to insulin therapy from physician's perspective was the treatment cost; 4.8% felt that the major barriers to achieve optimum diabetic care in practice was loss to follow-up followed by lack of counselling (3.9%) and treatment compliance (3.6%).Conclusion:DiabCare India 2011 has shown that type 2 diabetes sets in early in Indians and glycaemic control is often sub-optimal in these patients. These results indicate a need for more structured intervention at an early stage of the disease and need for increased awareness on benefits of good glycaemic control. It cannot be overemphasized that the status of diabetes care in India needs to be further improved. (ClinTrials.gov identifier: NCT01351922)

Real-World Insulin Treatment Persistence among Patients with Type 2 Diabetes

To evaluate real-world treatment persistence among patients with type 2 diabetes mellitus (T2DM) initiating treatment with insulin. Patient-level data were pooled from 3 previously published observational retrospective studies evaluating patients with T2DM who were previously on oral antidiabetic drugs (OADs) and initiated with a basal analog insulin (insulin glargine or insulin detemir). Treatment persistence was defined as remaining on the study drug during the 1-year follow-up period without discontinuation or switching after study drug initiation. Analyses were conducted to identify baseline factors associated with persistence with insulin therapy and to estimate the association between insulin treatment persistence and patients' clinical and economic outcomes during the follow-up period. A total of 4,804 patients with T2DM (insulin glargine: n = 4,172, insulin detemir: n = 632) were included. The average insulin persistence rate over the 1-year follow-up period was 65.0%. A significantly higher persistence rate was associated with older age, initiation with insulin glargine using either disposable pens or vial-and-syringe, and with baseline exenatide or sitagliptin use. Higher insulin treatment persistence was also associated with lower hemoglobin A1c (A1C) at follow-up, a greater reduction in A1C from baseline, and lower health care utilization. In real-world settings, treatment persistence among patients with T2DM initiating basal insulin is influenced by the type of insulin and patient factors. Greater insulin treatment persistence is linked to improved clinical outcomes and reduced health care utilization.

Efficacy and Safety of Insulin Glargine in Type 2 Diabetic Patients with Renal Failure

Aim and Background: In patients with type 2 diabetes mellitus complicated with renal failure achieving good glucose control and reduction of risk of hypoglycemia should be balanced. The aim of this study was to determine the safety and efficacy of insulin glargine in type 2 diabetic patients with diabetic nephropathy. Methods: A total of 89 subjects with type 2 diabetes (mean age 62.9 ± 10.7 and diabetes duration 13.9 ± 7.6 years) who had diabetic nephropathy (mean Glomerular FiltrationR [GFR] 34.1 ± 11.5 ml/min) were included in the study. Patients who were not optimally controlled or experienced frequent hypoglycemia on Oral Antidiabetic Drugs (OAD) or NPH insulin received insulin glargine at bedtime. The starting dose was 0.1 unit /Kg and adjusted to obtain target fasting blood glucose (5-7.2 mmol/l). The medical records were obtained before and 2 and 4 months after beginning insulin glargine. Results: At the end of four month treatment period, significant reduction in glycated hemoglobin (HbA 1 c) was observed (from 8.4% ± 1.6 to 7.7% ± 1.2) (p<0.001). The treatments were associated with significant reduction in fasting glucose levels (from 159.7 ± 67 to 119.4 ± 28.4mg/dl) (p<0.001).Patients’ Body Mass Index (BMI) did not increase at the end of study (26.2 ± 3.9 and 26.2 ± 3.8 kg/m2) (p=0.96). Mild symptomatic hypoglycemia was seen in 12.5% of subjects. No other side effects were noted throughout the study.

Improved glycaemic control with BIAsp 30 in insulin-naïve type 2 diabetes patients inadequately controlled on oral antidiabetics: subgroup analysis from the IMPROVE study

Objective:The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs).Methods:IMPROVE is a 26-week, open-label, non-randomised, international observational study in type 2 diabetes patients prescribed BIAsp 30 in routine clinical practice. The total cohort comprised 52 419 patients from various pre-study therapies. Here results from the subgroup of previously insulin-naïve patients are reported. Changes in glycated haemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of patients achieving HbA1c < 7.0%, and rates of major and minor hypoglycaemic events were recorded. Treatment satisfaction was assessed using a validated questionnaire.Results:A total of 29 160 insulin-naïve patients were included; mean age 55.6 years, diabetes duration 7.3 years, baseline HbA1c 9.24%. Significant reductions were seen for HbA1c (−2.12%; p < 0.0001), FBG (−4.07 mmol/L; p < 0.0001) and PPBG after all meals (mean: −5.27 mmol/L; p < 0.0001); 39.2% of patients achieved HbA1c < 7.0% without hypoglycaemia. Better glycaemic control was seen in patients treated with BIAsp 30 twice-daily (BID) both at baseline and final visit, or BID at baseline and three-times daily at final visit, compared with other regimens. The rate of major hypoglycaemic events decreased significantly, while the rate of minor hypoglycaemic events increased. Better glycaemic control and a lower rate of minor hypoglycaemia were observed in patients using BIAsp 30 without OADs than with OADs. There was no clinically relevant change in weight (−0.07 kg; p < 0.0001). At final visit, 59.7% of patients were extremely/very satisfied with treatment, compared with 10.2% at baseline.Conclusions:This open-label, non-randomised, observational study demonstrated that initiating insulin therapy with BIAsp 30 significantly improved glycaemic control in insulin-naïve patients previously poorly controlled on OADs. The rate of major hypoglycaemia was reduced and treatment satisfaction increased after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved with BIAsp 30 without OAD compared to with OAD.

Once-daily insulin detemir in a cohort of insulin-naïve patients with type 2 diabetes: a sub-analysis from the PREDICTIVE study

ABSTRACTObjective: PREDICTIVE is a large, observational study of the empirical use of insulin detemir in patients with type 1 or type 2 diabetes (T1DM/T2DM). This post hoc analysis evaluates insulin-naïve patients with T2DM uncontrolled on oral antidiabetic drugs (OADs) who were initiated and remained on once-daily insulin detemir for 12 weeks.* Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation; Novo Nordisk A/S, Bagsvaerd, DenmarkResearch design and methods: This observational, multinational, multi-center, open-label prospective study evaluated the efficacy and safety of insulin detemir in 1653 insulin-naïve patients with T2DM (mean age 60.8 ± 10.9 years, BMI 29.8 ± 4.8 kg/m2, and HbA1C 8.82 ± 1.50%). Statistical comparisons were made between baseline and 12-week follow up data. Our study was subject to the usual limitations of observational studies.Main outcome measures: Endpoints were: incidence of serious adverse drug reactions, including number of hypoglycemic events (total, major, and nocturnal), glycemic parameters, and weight change.Results: Following insulin initiation, no significant change occurred in the number of nocturnal hypoglycemic events or total hypoglycemic events (p = 0.4513), and no serious adverse drug reactions were observed during the 12 weeks of treatment. HbA1C decreased by a mean 1.25% (SD ± 1.25%; p < 0.0001), with 30% of patients (n = 383) achieving HbA1C <7% at 12 weeks. Mean changes in fasting blood glucose and fasting blood glucose variability were –3.62 mmol/L (SD ± 2.93; p < 0.0001) and −0.48 mmol/L (SD ± 1.03; p < 0.0001), respectively. Body weight decreased by a mean 0.5 kg (SD ± 3.3; p < 0.0001), with weight loss or no weight change occurring in a substantial percentage of patients in each BMI category (<25, 25–30, 30–35, and >35 kg/m2). Patients with higher baseline BMI lost the most weight, with the greatest weight loss (–1.20 kg) reported in those with BMI >35 kg/m2.Conclusions: Empirical use of insulin detemir as an insulin initiation strategy can improve glycemic control with good tolerability, including a low risk of hypoglycemia and a weight benefit, in a majority of insulin-naïve patients uncontrolled on OADs.

Comparison of glycaemic control in patients with Type 2 diabetes on basal insulin and fixed combination oral antidiabetic treatment: results of a pilot study

This randomised, open-label, two-way cross-over study compared the coefficient of variance (CV) of fasting and postprandial blood glucose (FBG and PPBG) with insulin glargine (glargine) versus neutral protamine Hagedorn (NPH) insulin treatment in patients with Type 2 diabetes (T2DM). Patients (N=20) on oral antidiabetic drugs (OADs) were treated with NPH (at bedtime) or glargine (at dinnertime) for 12 weeks of each cross-over treatment period; OADs were continued. The FBG CV was calculated from self-monitored BG values and PPBG using venous blood samples, or continuous glucose monitoring system (CGMS). Both insulins provided similar improvements in glycaemic control; however, PPBG was significantly lower after a standard meal test (performed at 13:00 h the day after insulin injection) with glargine versus NPH (p=0.02). Thirteen versus 15 patients experienced >or=1 episode of hypoglycaemia with glargine versus NPH. The results suggest that glargine plus OADs is more effective in reducing PPBG fluctuations during the day than NPH plus OADs.

Unmet needs among patients with Type 2 diabetes and secondary failure to oral anti-diabetic agents

Secondary failure is defined as a deterioration of glucose control in patients with Type 2 diabetes on oral antidiabetic drugs (OAD), mainly due to the progressive decline in beta-cell function and reduction in insulin secretion. The consequent hyperglycemia is the most important determinant for the development of microvascular and macrovascular complications, so that an early recognition of this phenomenon can improve long-term outcomes. The recent lowering of target glycosylated hemoglobin (HbA1c) levels by international guidelines not only emphasises the importance of tight glycemic control, but also means that secondary failure to OAD will occur much sooner and is almost unavoidable. Accordingly, in the last years, new different therapeutic strategies were explored to improve the treatment of this condition. The aim of this review is to examine current approaches for treating patients with secondary failure, barriers to achieving and maintaining glycemic control, and recent evidence for emerging therapies which may represent a valid therapeutic option in subjects failing on oral hypoglycemic agents by acting mainly, but not only, at a beta-cell level. In particular, we will focus on the co-administration of OAD plus a novel drug class known as incretin mimetics (e.g. exenatide and liraglutide), which target insulin secretion, and on thiazolidinediones, which act on insulin resistance. Only incretin-mimetics have a lowering HbA1c action, due to the improvement in beta-cell function, which is coupled to significant weight loss. Even if these new options seem to improve the outcome of secondary failure, further investigation is needed to confirm positive results in the long term.

Insulin detemir improves glycaemic control without weight gain in insulin-naïve patients with type 2 diabetes: subgroup analysis from the PREDICTIVETM study

Predictable Results and Experience in Diabetes through Intensification and Control to Target: an International Variability Evaluation (PREDICTIVE) is a multi-national, open-label, prospective, observational study assessing the safety and efficacy of insulin detemir in clinical practice. This post hoc subanalysis evaluates insulin-naïve patients on oral antidiabetic drugs (OADs) who were initiated on insulin detemir as basal therapy (+/- OADs). The European cohort of the PREDICTIVE study currently includes 20,531 patients (12,981 with type 2 diabetes) who were prescribed insulin detemir and followed up for 12, 26 or 52 weeks. Here, we report data from a subgroup of 2377 OAD-treated, insulin-naïve type 2 diabetes patients for a mean follow-up of 14.4 weeks. Patients were prescribed insulin detemir as basal therapy (+/- OADs) by their physician, as part of routine clinical care. Results were reported in comparison with baseline observations. One serious adverse drug reaction was reported, which was a major hypoglycaemic episode. Treatment with insulin detemir (+/- OADs) significantly reduced mean haemoglobin A(1c) (HbA(1c)) (-1.3%; p < 0.0001), fasting glucose (-3.7 mmol/l; p < 0.0001), and within-patient fasting glucose variability (-0.5 mmol/l; p < 0.0001). In the majority of patients (82%), these improvements in glycaemic control were achieved with once daily administration of insulin detemir. There was a small reduction in mean body weight (-0.7 kg; p < 0.0001), which was most apparent in patients with a higher body mass index (BMI) at baseline. A significant negative relationship between weight change and baseline BMI was observed (greater the BMI, greater the weight reduction). Multiple regression analysis showed that BMI and HbA(1c) at baseline, and change in HbA(1c), were all predictors for weight change (p < 0.0001 for all), with BMI being the strongest predictor. Patients with type 2 diabetes naïve to insulin can be effectively treated with once-daily insulin detemir (+/- OADs) to achieve improved glycaemic control with no adverse effect on weight and a low risk of hypoglycaemia. These short-term results are consistent with the findings of clinical trials.

Improving glycemic control with insulin detemir using the 303 Algorithm in insulin naïve patients with type 2 diabetes: a subgroup analysis of the US PREDICTIVE 303 study

PREDICTIVE 303 was a 26-week, prospective, randomized, open-label, multi-center study in patients with type 2 diabetes that investigated whether patient-driven adjustments of insulin detemir doses using the 303 Algorithm achieved similar glycemic control compared to standard-of-care, physician-driven adjustments in doses. This post hoc sub-analysis evaluates insulin naïve patients on oral anti-diabetic drugs (OADs) who were directed to start on once-daily insulin detemir as add-on therapy to any other glucose-lowering regimens.Patients in the 303 Algorithm group were instructed to adjust their detemir dose every 3 days based on mean fasting plasma glucose (FPG) values using a simple algorithm: mean FPG < 80 mg/dL, reduce dose by 3 units; between 80-110mg/dL, no change; > 110mg/dL, increase by 3 units. Physicians adjusted the detemir dose for patients in the Standard-of-care group according to their usual practice. No control insulin was used for comparison to insulin detemir.Reductions in glycosylated hemoglobin (HbA(1c)) from baseline were similar between those patients in the 303 Algorithm and Standard-of-care groups (-1.1 and -1.0%, respectively; between group p = 0.0933); patients in the 303 Algorithm group achieved a greater reduction in FPG. Patients in both groups experienced a similar, low rate of hypoglycemia. Over 95% and 92% of patients, respectively, used detemir once daily.These data indicate that patients with type 2 diabetes naïve to insulin can effectively implement the 303 Algorithm to initiate and adjust a once-daily dose of insulin detemir to achieve improvements in glycemic control.

Improving glycemic control with insulin detemir using the 303 Algorithm in insulin naïve patients with type 2 diabetes: a subgroup analysis of the US PREDICTIVE 303 study

ABSTRACTObjective: PREDICTIVE 303 was a 26-week, prospective, randomized, open-label, multi-center study in patients with type 2 diabetes that investigated whether patient-driven adjustments of insulin detemir doses using the 303 Algorithm achieved similar glycemic control compared to standard-of-care, physician-driven adjustments in doses. This post hoc sub-analysis evaluates insulin naïve patients on oral anti-diabetic drugs (OADs) who were directed to start on once-daily insulin detemir as add-on therapy to any other glucose-lowering regimens.Methods: Patients in the 303 Algorithm group were instructed to adjust their detemir dose every 3 days based on mean fasting plasma glucose (FPG) values using a simple algorithm: mean FPG < 80mg/dL, reduce dose by 3 units; between 80–110 mg/dL, no change; >110 mg/dL, increase by 3 units. Physicians adjusted the detemir dose for patients in the Standard-of-care group according to their usual practice. No control insulin was used for comparison to insulin detemir.Results: Reductions in glycosylated hemoglobin (HbA1c) from baseline were similar between those patients in the 303 Algorithm and Standard-of-care groups (−1.1 and −1.0%, respectively; between group p = 0.0933); patients in the 303 Algorithm group achieved a greater reduction in FPG. Patients in both groups experienced a similar, low rate of hypoglycemia. Over 95% and 92% of patients, respectively, used detemir once daily.Conclusion: These data indicate that patients with type 2 diabetes naïve to insulin can effectively implement the 303 Algorithm to initiate and adjust a once-daily dose of insulin detemir to achieve improvements in glycemic control.

Efficacy and Treatment Satisfaction of Once-Daily Insulin Glargine Plus One or Two Oral Antidiabetic Agents Versus Continuing Premixed Human Insulin in Patients with Type 2 Diabetes Previously on Long-term Conventional Insulin Therapy: The Switch Pilot Study

Addition of the long-acting basal human insulin analogue insulin glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic control on oral antidiabetic drugs (OADs) alone has previously been evaluated as effective, safe and convenient. This pilot study aimed to establish whether insulin glargine plus OADs is effective in Type 2 diabetes patients previously poorly controlled on premixed insulin therapy. In an open, controlled, randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age 65.6+/-9.2 years; diabetes duration 15.3+/-7.6 years; insulin therapy duration 4.2+/-1.7 years, body mass index 31.4+/-2.9 kg/m2) with Type 2 diabetes (HbA1c>or=8.0%) on premixed human insulin (75/25 or 70/30) were randomized to once-daily morning insulin glargine plus glimepiride (Group A; n=17), insulin glargine plus glimepiride and metformin (Group B; n=18) or premixed insulin (Group C; n=17). Glycaemic control and incidence of hypoglycaemia were evaluated. HbA1c decreased significantly from baseline in Groups A and B, but not in Group C; (Group A: 7.87+/-0.66%, -0.35%, p=0.013; Group B: 7.44+/-0.92%, -0.69%, p=0.0057; Group C: 7.83+/-1.13%, -0.25%, p=0.32). There were no between-treatment differences at endpoint in HbA1c, fasting blood glucose, mean daily blood glucose or symptomatic hypoglycaemia (mean events/patient: Group A, 2.2; Group B, 2.3; Group C, 2.0). At endpoint, 88% of patients in Group A, 81% in Group B and 94% in Group C opted to continue with their assigned regimen. This pilot study is the first prospective study to show that switching from premixed insulin to insulin glargine plus OAD treatment resulted in similar glycaemic control and treatment satisfaction. The results support the need for prospective examination in a larger-scale clinical study in patients with long-standing Type 2 diabetes and sub-optimal glycaemic control previously using a conventional premixed insulin regimen.

Efficacy and Treatment Satisfaction of Once-daily Insulin Glargine Plus One or Two Oral Antidiabetic Agents Versus Continuing Premixed Human Insulin in Patients with Type 2 Diabetes Previously on Long-term Conventional Insulin Therapy: The SWITCH Pilot Study

Addition of the long-acting basal human insulin analogue insulin glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic control on oral antidiabetic drugs (OADs) alone has previously been evaluated as effective, safe and convenient. This pilot study aimed to establish whether insulin glargine plus OADs is effective in Type 2 diabetes patients previously poorly controlled on premixed insulin therapy. In an open, controlled, randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age 65.6+/-9.2 years; diabetes duration 15.3+/-7.6 years; insulin therapy duration 4.2+/-1.7 years, body mass index 31.4+/-2.9 kg/m(2)) with Type 2 diabetes (HbA (1c)> or =8.0%) on premixed human insulin (75/25 or 70/30) were randomized to once-daily morning insulin glargine plus glimepiride (Group A; n=17), insulin glargine plus glimepiride and metformin (Group B; n=18) or premixed insulin (Group C; n=17). Glycaemic control and incidence of hypoglycaemia were evaluated. HbA (1c) decreased significantly from baseline in Groups A and B, but not in Group C; (Group A: 7.87+/-0.66%, -0.35%, p=0.013; Group B: 7.44+/-0.92%, -0.69%, p=0.0057; Group C: 7.83+/-1.13%, -0.25%, p=0.32). There were no between-treatment differences at endpoint in HbA (1c), fasting blood glucose, mean daily blood glucose or symptomatic hypoglycaemia (mean events/patient: Group A, 2.2; Group B, 2.3; Group C, 2.0). At endpoint, 88% of patients in Group A, 81% in Group B and 94% in Group C opted to continue with their assigned regimen. This pilot study is the first prospective study to show that switching from premixed insulin to insulin glargine plus OAD treatment resulted in similar glycaemic control and treatment satisfaction. The results support the need for prospective examination in a larger-scale clinical study in patients with long-standing Type 2 diabetes and sub-optimal glycaemic control previously using a conventional premixed insulin regimen.

Efficacy of insulin glargine and glimepiride in controlling blood glucose of ethnic Japanese patients with type 2 diabetes mellitus

Background To evaluate the efficacy and safety of glimepiride plus insulin glargine in ethnic Japanese patients with type 2 diabetes mellitus (T2DM). Methods This 24-week, open-label, single-arm study was conducted in eight centers in Brazil. One hundred ethnic Japanese T2DM patients with inadequate glycemic control [HbA 1c: 8.0–11.0% and fasting plasma glucose (FPG) ≥ 140 mg/dL] on oral antidiabetic drugs (OADs) were enrolled. Patients were treated once daily with glimepiride 3 mg (morning) and glargine (bedtime) with dose titration to achieve FPG 72–100 mg/dL. Results At Week 24, the mean dose of glargine was 37.6 IU/day. There were significant decreases ( p < 0.0001) compared with baseline, for mean HbA 1c (1.5%), mean FPG (88.3 mg/dL) ( p < 0.0001), mean PPG (112.0 mg/dL), and mean fasting C-peptide (1.14 ng/mL). Peptide index (peak − basal/basal) in carbohydrate challenge test increased by 2.24 units. No severe adverse events, including severe hypoglycemia were reported. Conclusions Our study suggests that combined therapy of insulin glargine and glimepiride should be considered for T2DM patients who have unsatisfactory response to previous OAD treatment.