Antidiabetic Failure Research Articles

Real-World Study on Effectiveness of Insulin Glargine U300 After Oral Antidiabetic Drug Failure in Patients with Type 2 Diabetes in the Gulf Region.

The effectiveness and safety of long-acting insulin glargine U300 (Gla-300), in patients with type2 diabetes mellitus (T2DM) requiring insulin, has not been reported in the Gulf region. Insulin-naïve patients with T2DM, uncontrolled on OADs, and prescribed Gla-300 were followed up in a 12-month prospective observational study. Gla-300 was titrated to glycemic targets. The primary endpoint (achieving glycemic targets) was evaluated at month 6 of treatment. The need for treatment intensification, safety, and patient-reported outcomes (PRO) were also reported. The study included 412 patients (61.7% men; age 52.2 ± 11.1years and T2DM duration 10.7 ± 6.8years). Almost 50% were on more than 3 OADs, mostly biguanides, sulfonylureas, and dipeptidyl-peptidase-4 inhibitors. Baseline HbA1c level was 9.2% ± 1.1% and targets were set at 6.9% ± 0.4%. Baseline fasting plasma glucose was 11.5 ± 3.8mmol/l. Fifty-seven patients (13.8%) achieved glycemic targets at month 6, hindered by baseline HbA1c ≥ 10%, frequent co-morbidities, older age, suburban/rural residence, and full-time employment. Levels of HbA1c dropped progressively by 0.96% ± 0.07% (month 3), 1.29% ± 0.08% (month 6), and 1.76% ± 0.06% (month 12). Gla-300 dose was 17.0 ± 9.0IU/day at baseline, 24.6 ± 9.6 IU/day at month 3, 28.5 ± 9.9IU/day at month 6, and 30.7 ± 10.7IU/day at month 12. Three patients experienced non-severe hypoglycemia and a slight decrease in body weight and PROs improved. In the Gulf, Gla-300 in patients with T2DM uncontrolled on OADs improved glycemic control, with low rates of hypoglycemia and improved PROs. Gla-300 dose up-titration from baseline to month 6 did not, however, result in a vast proportion of patients achieving their pre-determined HbA1c targets. ClinicalTrials.gov identifier: NCT03703869.

A 12-Month Prospective Observational Study Assessing the Real-World Clinical Effectiveness and Safety of Insulin Glargine 300 U/mLInitiation After Oral Antidiabetic Drug Failure in Insulin-Naïve Individuals with Type 2 Diabetes Mellitus in Egypt: A Posthoc Subgroup Analysis [ATOS Study

A 12-Month Prospective Observational Study Assessing the Real-World Clinical Effectiveness and Safety of Insulin Glargine 300 U/mLInitiation After Oral Antidiabetic Drug Failure in Insulin-Naïve Individuals with Type 2 Diabetes Mellitus in Egypt: A Posthoc Subgroup Analysis [ATOS Study

Real-world Clinical Effectiveness on Glycaemic Parameters, Safety and Additional Benefits of Glargine U300 (Toujeo®) Initiation after Oral Antidiabetic Drug Failure in Insulin-naïve Patients with type 2 Diabetes Mellitus.

Several studies have proved the advantages of second-generation insulin analogs in lowering intra-individual variability in plasma insulin levels, flexibility in dosing, a sustained glucose-lowering effect, and decreasing the risk of hypoglycemia. Glargine 300 is one of the newer second-generation basal insulin analogs to have been approved for both type 1 and 2 diabetes. The present study aims to assess the real-world clinical effectiveness and safety of Glargine U300 (Toujeo®) initiation after oral antidiabetic drug failure in insulin-naïve patients with T2DM. A prospective, observational study was conducted where participants were interviewed regarding their basic demographics, body weight, and treatment details. Glycemic parameters (HbA1C%, Fasting Plasma Glucose, and Post Prandial Blood Glucose) were observed in the initial 6 months, and changes were noted and compared. Any hypoglycemic events or other complications were also noted. Data collected were statistically analyzed. The study included a total of 188 patients. Treatment with glargine 300 significantly reduced the mean HbA1C level from 9.78% at baseline to 7.90% at the end of 6 months of treatment (p < 0.001). 10.60% of patients achieved the glycemic target of ≤7.0% by the end of 6 months, while only 6.90% were within the target range at baseline. Similarly, significant reduction in FPG was observed at the end of 6 months treatment period with Glargine U300. A significant increase in dose requirement was observed throughout the study phase (p < 0.001). Incidence of hypoglycemia was noted in 2.12% of subjects. The lower incidence statistics of hypoglycemia coupled with sustained positive glycemic effects, stands out to be a prominent advantage of Glargine U300 over its other congeners.

Reliable prediction of anti-diabetic drug failure using a reject option

The medical care for patients with type 2 diabetes generally involves ingestion of oral hypoglycemic agents in order to lower their glucose level. When predicting the result of the medication using a classification approach, high prediction accuracy of the classifier is essential because of high misclassification costs. The application of a reject option to this approach supports more accurate prediction, allowing for human experts to examine when the classifier is unreliable to predict. In this paper, we propose a reject option framework based on heterogeneous ensemble learning through a two-phase fusion. The first phase is to calculate confidence scores, which are used to determine whether to predict, and the second phase is to derive final prediction results by fusing the outputs from multiple heterogeneous classifiers. We confirm the effectiveness of the proposed method to the anti-diabetic drug failure prediction problem through experiments on actual electronic medical records data of type 2 diabetes. The proposed method yields a better trade-off between accuracy and rejection than other reject options with statistical significance. A lower prediction error is obtained for the same degree of rejection. We obtained desirable accuracy for the anti-diabetic drug failure problem by applying the proposed reject option, which allows using the classification approach in practice. The accurate prediction of drug failure at the moment of prescription can assist clinical decisions for patients. In addition, in-depth analysis can be considered for those prescriptions that are predicted as failure or rejected.

An efficient and effective ensemble of support vector machines for anti-diabetic drug failure prediction

The treatment of patients with type 2 diabetes is mostly based on drug therapies, aiming at managing glucose levels appropriately. As the number of patients with type 2 diabetes continually increases worldwide, predicting drug treatment failure becomes an important issue. Support vector machine (SVM) can be a good method for the anti-diabetic drug failure prediction problem; however, it is difficult to train SVM on large-scale medical datasets directly because of its high training time complexity O(N3). To address the limitation, we propose an efficient and effective ensemble of SVMs, called E3-SVM. The proposed method excludes superfluous data points when constructing an SVM ensemble, thereby yielding a better classification performance. The proposed method consists of two phases. The first phase is to select the data points that are likely to be the support vectors by applying data selection methods. The second phase is to construct an SVM ensemble using the selected data points. We demonstrated the efficiency and effectiveness of the proposed method using the real-world dataset of the anti-diabetic drug failure prediction problem for type 2 diabetes. Experimental results show that the proposed method requires less training time to achieve comparable success, compared to the conventional SVM ensembles. Moreover, the proposed method obtains more reliable prediction results for each independent run of constructing an ensemble. In conclusion, firstly, the proposed method provides an efficient and effective way to use SVM for large-scale datasets. Secondly, we confirmed the suitability of SVM for the anti-diabetic drug failure prediction problem with an accuracy of about 80%.

Efficacy and Safety of Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients with Type 2 Diabetes Mellitus: A Randomized Placebo-Controlled Study

There is a growing interest in cell-based therapies in T2DM as β-cell failure is progressive and inexorable with the advancing duration of disease. This prospective, randomized, single-blinded placebo-controlled study evaluates the efficacy and safety of autologous bone marrow-derived stem cell transplantation (ABMSCT) in T2DM. Twenty-one patients with triple oral antidiabetic drug failure and requiring insulin ≥0.4 IU per kg per day with HbA1c <7.5% were randomly assigned to an intervention (n = 11) and control group (n = 10) and followed for 12 months. Patients in the intervention group received ABMSCT through a targeted approach, and after 12 weeks, a second dose of stem cells was administered through the antecubital vein after mobilization with G-CSF, while the control group underwent a sham procedure. The primary end point was a reduction in insulin requirement by ≥50% from baseline while maintaining HbA1c <7%. Nine out of the 11 (82%) patients in the intervention group achieved the primary end point, whereas none of the patients in the control group did over the study period (p = 0.002). The insulin requirement decreased by 66.7% in the intervention group from 42.0 (31.0‐64.0) IU per day to 14.0 (0.0‐30.0) IU per day (p = 0.011), while in controls it decreased by 32.1% from 40.5 (31.8‐44.3) IU per day to 27.5 (23.5‐33.3) IU per day (p = 0.008) at 12 months. The reduction in insulin requirement was significantly more in the intervention group compared to controls at both 6 (p = 0.001) and 12 months (p = 0.004). There was a modest but nonsignificant increase in HbA1c (%) in cases from 6.9% (6.4‐7.2%) to 7.1% (6.6‐7.5%) as well as in controls from 6.9% (6.2‐7.0%) to 7.0% (6.9‐7.5%). Ten out of 11 (91%) patients could maintain HbA1c <7% in the intervention group, whereas 6 out of 10 did (60%) in the control group (p = 0.167). The glucagon-stimulated C-peptide significantly increased in treated cases compared to controls (p = 0.036). The decrease in insulin requirement positively correlated with stimulated C-peptide (r = 0.8, p = 0.001). In conclusion, ABMSCT results in a significant decrease in the insulin dose requirement along with an improvement in the stimulated C-peptide levels in T2DM. However, a greater number of patients with a longer duration of follow-up are required to substantiate these observations.

Common Standards of Basal Insulin Titration in T2DM

Type 2 diabetes mellitus has become a worldwide major health problem, and the number of people affected is steadily increasing. Thus, not all patients suffering from the disease can be treated by specialized diabetes centers or outpatient clinics, but by primary care physicians. The latter, however, might have time constraints and have to deal with many kinds of diseases or with multimorbid patients, so their focus is not so much on lowering high blood glucose values. Thus, the physicians, as well as the patients themselves, are often reluctant to initiate and adjust insulin therapy, although basal insulin therapy is considered the appropriate strategy after oral antidiabetic drug failure, according to the latest international guidelines. A substantial number of clinical studies have shown that insulin initiation and optimization can be managed successfully by using titration algorithms-even in cases where patients themselves are the drivers of insulin titration. Nevertheless, tools and strategies are needed to facilitate this process in the daily life of both primary health care professionals and patients with diabetes.

Efficacy and safety of patient-directed titration of once-daily pre-dinner premixed biphasic insulin aspart 70/30 injection in Japanese type 2 diabetic patients with oral antidiabetic drug failure: STEP-AKITA study.

Aims/Introduction: To clarify clinical characteristics related to optimal glycemic control achieved after adding once-daily pre-dinner biphasic insulin aspart 70/30 (BIAsp 30) in Japanese type 2 diabetic (T2D) patients with oral antidiabetic drug (OAD) failure. Under this regimen, we evaluated changes in HbA1c levels and daily self-monitoring blood glucose (BG) profiles, as well as the incidences of hypoglycemia and retinopathy progression. The patients adjusted BIAsp 30 dosages themselves every 3-4 days according to a pre-determined algorithm to achieve fasting BG levels of 101-120 mg/dL. HbA1c levels were expressed as Japan Diabetes Society values. Of 29 enrolled patients, 22 (HbA1c levels, 8.5 ± 1.5% [mean ± SD]) and 20 patients completed the 16- and 24-week follow-up, respectively. At 16 weeks 68.2 and 45.5%, and at 24 weeks 80.0 and 35% of patients had achieved HbA1c levels of <7.0 and <6.5%, respectively. The patients who had achieved optimal glycemic control, including daytime postprandial BG profiles after treatment, had lower post-breakfast BG excursions at baseline, shorter diabetes durations and younger age. No severe hypoglycemic episodes were recorded. Progression of retinopathy was observed in 3 of the 29 enrolled patients. Lower post-breakfast BG excursions, shorter diabetes duration and younger age in Japanese T2D patients with OAD failure might warrant optimal glycemic control with safety after adding once-daily pre-dinner BIAsp 30 initiating regimen. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00062.x, 2010).

Rosiglitazone versus bedtime insulin in the treatment of patients with conventional oral antidiabetic drug failure: A 1-year randomized clinical trial

This study was conducted to evaluate the efficacy and tolerability of rosiglitazone in the treatment of patients with secondary oral antidiabetic drug (OAD) failure and to directly compare its use with bedtime insulin. A total of 112 Chinese patients with type 2 diabetes and conventional OAD failure were recruited. Patients were randomly assigned to treatment with rosiglitazone or bedtime isophane insulin; they continued to take their original oral antidiabetic drugs. Glycemic index, other clinical profiles, and tolerability were assessed during treatment and 1 y after add-on treatment was provided. Among the 112 patients, mean age (+/-SD) was 58.2+/-11.0 y (median, 58 y; range, 37 to 84 y). Both rosiglitazone (n=56) and insulin (n=56) significantly improved fasting glucose (2.4 and 3.7 mmol/L, respectively) and hemoglobin A1c concentrations (1.1% and 1.3%, respectively). Both therapies increased body mass index after 1 y of treatment (0.9 and 0.8 kg/m2, respectively). Only rosiglitazone increased high-density lipoprotein cholesterol concentrations (0.1 mmol/L). Four patients (7.1%) who were given rosiglitazone developed adverse effects (2, ankle edema, and 2, gastrointestinal disturbance). Six insulin-treated patients (10.7%) described adverse effects (5, early morning hypoglycemia, and 1, anxiety). Investigators concluded that in Chinese patients with type 2 diabetes and secondary conventional OAD failure, 1 y of treatment with rosiglitazone or bedtime insulin added to the regular regimen resulted in similar improvements in glycemic control. Rosiglitazone was also associated with improved high-density lipoprotein cholesterol levels. The addition of rosiglitazone may offer a safe and effective alternative to bedtime insulin treatment.