Diabetes Therapy

Efficacy of Vildagliptin Added to Continuous Subcutaneous Insulin Infusion (CSII) in Hospitalized Patients with Type 2 Diabetes Abstract Introduction The aim of this study was to compare the efficacy of vildagliptin as add-on therapy to short-term continuous subcutaneous insulin infusion (CSII) with CSII monotherapy in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods A total of 200 hospitalized patients with inadequately controlled T2DM were randomized into groups, with one group receiving CSII monotherapy (CSII group, n =100) and the other group receiving CSII plus vildagliptin as add-on (CSII + Vig group, n = 100). Of these, 191 completed the 7-day trial (CSII group, n = 99; CSII + Vig group, n = 92) and included in the analysis. The glycemic control and variability of the patients were measured using all-day capillary blood glucose (BG) monitoring. Weight and fasting C-peptide levels were evaluated before and after the interventions. Results Mean BG concentrations during the whole treatment period were lower and the time to reach target BG was reduced in the CSII + Vig group compared with the CSII group (9.89 ± 3.37 vs. 9.46 ± 3.23 mmol/L, P < 0.01; 129 ± 4 vs. 94 ± 5 h, P < 0.01, respectively). Similarly, the indicators of glycemic variability, namely the standard deviation of BG and the largest amplitude of glycemic excursion, were significantly decreased in the CSII + Vig group compared with the CSII group (2.68 ± 1.05 vs. 2.39 ± 1.00 mmol/L, P < 0.01; 7.19 ± 2.86 vs. 6.23 ± 2.73 mmol/L, P < 0.01, respectively). Conclusions Short-term CSII with vildagliptin as add-on therapy may be an optimized treatment for hospitalized patients with T2DM compared with short-term CSII monotherapy.

Application of Machine Learning Models to Evaluate Hypoglycemia Risk in Type 2 Diabetes Abstract Introduction To identify predictors of hypoglycemia and five other clinical and economic outcomes among treated patients with type 2 diabetes (T2D) using machine learning and structured data from a large, geographically diverse administrative claims database. Methods A retrospective cohort study design was applied to Optum Clinformatics claims data indexed on first antidiabetic prescription date. A hypothesis-free, Bayesian machine learning analytics platform (GNS Healthcare REFS™: Reverse Engineering and Forward Simulation) was used to build ensembles of generalized linear models to predict six outcomes defined in patients’ 1-year post-index claims history, including hypoglycemia, antidiabetic class persistence, glycated hemoglobin (HbA1c) target attainment, HbA1c change, T2D-related inpatient admissions, and T2D-related medical costs. A unified set of 388 variables defined in patients’ 1-year pre-index claims history constituted the set of predictors for all REFS models. Results The derivation cohort comprised 453,487 patients with a T2D diagnosis between 2014 and 2017. Patients with comorbid conditions had the highest risk of hypoglycemia, including those with prior hypoglycemia (odds ratio [OR] = 25.61) and anemia (OR = 1.29). Other identified risk factors included insulin (OR = 2.84) and sulfonylurea use (OR = 1.80). Biguanide use (OR = 0.75), high blood glucose (> 125 mg/dL vs. < 100 mg/dL, OR = 0.47; 100–125 mg/dL vs. < 100 mg/dL, OR = 0.53), and missing blood glucose test (OR = 0.40) were associated with reduced risk of hypoglycemia. Area under the curve (AUC) of the hypoglycemia model in held-out testing data was 0.77. Patients in the top 15% of predicted hypoglycemia risk constituted 50% of observed hypoglycemic events, 26% of T2D-related inpatient admissions, and 24% of all T2D-related medical costs. Conclusions Machine learning models built within high-dimensional, real-world data can predict patients at risk of clinical outcomes with a high degree of accuracy, while uncovering important factors associated with outcomes that can guide clinical practice. Targeted interventions towards these patients may help reduce hypoglycemia risk and thereby favorably impact associated economic outcomes relevant to key stakeholders.

Best Practices and Tools for Titrating Basal Insulins: Expert Opinion from an Indian Panel via the Modified Delphi Consensus Method Abstract Aim To develop an evidence-based expert group consensus document on the best practices and simple tools for titrating basal insulins in persons with type 2 diabetes mellitus (T2DM). Background Glycemic control is suboptimal in a large proportion of persons with T2DM, despite insulin therapy, thereby increasing the risk of potentially severe complications. Early initiation of insulin therapy and appropriate dose titration are crucial to achieving glycemic targets. Attitudes and practices among healthcare professionals (HCPs) and perceptions about insulin therapy among persons with diabetes contribute largely to suboptimal glycemic control. Improving HCP–patient communication, encouraging the use of additional educational tools, and providing support for the titration process to increase confidence, both at the initiation visit and at home, facilitate the optimization of dose titration. In Indian settings, specific guidelines and a consensus statement are lacking on the optimal insulin initiation dose, frequency of dose titration, and basal insulin profile needed to achieve optimal titration. In clinical practice, physicians and persons with diabetes often do not adhere to the titration algorithms that currently exist for the purpose of achieving optimal titration as they perceive these to be very cumbersome. In this context, a group of experts met at an advisory board meeting and arrived at a consensus on best practices for the titration of basal insulin in persons withT2DM in India, using the modified Delphi methodology. Review Results After a review of evidence and further discussions, the expert group provided recommendations on insulin initiation dose, ideal period for titration in practice, titration regimen for use in practice, basal insulin profile for titration, and choosing a self-monitoring blood glucose schedule for titration. Conclusions In the management of T2DM, insulin can be effectively titrated by following a few simple recommendations. The use of second-generation basal insulin aids in mitigating the risk of hypoglycemic events. The implementation of a simplified titration regimen is crucial to achieving glycemic targets and long-term treatment goals.

Correction to: The Association Between Phosphorylated Neurofilament Heavy Chain (pNF-H) and Small Fiber Neuropathy (SFN) in Patients with Impaired Glucose Tolerance In the original article, there was some error in Table 2. The correct table is given below.

Correction to: Optimising the Benefits of SGLT2 Inhibitors for Type 1 Diabetes In the original article, Associated Medical Education Section has been published mistakenly. It has been removed from the original publication.

Insulin Glargine 300 U/mL and Insulin Glulisine Treatment in Patients with Type 2 Diabetes: A Non-Interventional Study of Effectiveness in Routine Clinical Practice Abstract Introduction The EDITION development program confirmed that insulin glargine 300 U/mL (Gla-300) provides comparable glycemic control to insulin glargine 100 U/mL (Gla-100) but with lower hypoglycemia risk. Our study aimed to evaluate the effectiveness of Gla-300 in everyday practice. Methods This one-arm, non-interventional study included patients with type 2 diabetes who were switched to Gla-300-based basal-bolus therapy (BBT) and followed for 6 months. Indications for switching included inadequate glycemic control and/or hypoglycemic events with the previous regimen. Results Overall 229 patients were included, with mean age of 60.9 years. All glycemic variables improved between baseline and 6 months significantly (mean ± standard deviation [SD] hemoglobin A1c [HbA1c] from 8.9 ± 1.5% to 7.5 ± 1.1%, fasting blood glucose from 9.5 ± 3.1 mmol/L to 7.0 ± 2.1 mmol/L, postprandial blood glucose from 12.0 ± 3.8 mmol/L to 8.9 ± 2.5 mmol/L). Gla-300 doses were increased and mealtime insulin doses were unchanged. Rates of both non-severe and severe hypoglycemic events decreased significantly compared to pre-study and 6-month follow-up periods. Patients switched because of elevated HbA1c had higher baseline HbA1c and greater decrease in HbA1c paralleled with increase in insulin doses compared to those switched because of hypoglycemia. Conclusions In day-to-day practice, switching from human insulin to Gla-300-based BBT resulted in significant improvement in glycemic control and decrease in hypoglycemia risk.

Cost of Managing Type 2 Diabetes Before and After Initiating Dipeptidyl Peptidase 4 Inhibitor Treatment: A Longitudinal Study Using a French Public Health Insurance Database Abstract Introduction Diabetes is a growing epidemic that imposes a substantial economic burden on healthcare systems. This study aimed to evaluate the cost of managing type 2 diabetes (T2D) with dipeptidyl peptidase 4 inhibitors (DPP4Is) using real-world data. Method This longitudinal study used data from the French EGB (Echantillon Généraliste des Bénéficiaires) database. The annual average direct healthcare cost of treating patients with T2D was calculated 3 years prior and 3 years after initiation of DPP4I therapy. Actual total ambulatory and hospital care expenditure for the 3 years after DPP4I initiation was compared to projected costs. The distribution of costs across all care modalities was assessed over the 6-year period. Results Ambulatory and hospital care expenditure data for 919 patients with T2D starting DPP4I therapy alone or in combination in 2013 were analyzed. A total of 526 patients (57.2%) were still being treated with DPP4I 3 years after DPP4I initiation. Regardless of the treatment regimen, the ambulatory and hospital care costs increased above projected costs in the first year following DPP4I initiation, and then declined during the second and third years to levels in line with or below projected values for patients using DPP4Is as an add-on therapy. The increase in total expenditure in the first year following DPP4I initiation and the subsequent decline in costs in the second and third years were both associated with general trends in consumption across all aspects of patient care. Conclusion Despite an initial increase in healthcare expenditure, concomitant with reevaluation of patient care, this study showed that initiation of DPP4Is as an add-on therapy in French patients with T2D was associated with care expenditure that was in line or below predicted values within the 3 years following treatment initiation. Additional studies are required to evaluate the economic impact of the long-term treatment benefits.

Utility of Precision Medicine in the Management of Diabetes: Expert Opinion from an International Panel Abstract Aim The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management. Background The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations. Review Results After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most. Conclusion Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.

Impact of Switching from Twice-Daily Basal Insulin to Once-Daily Insulin Glargine 300 U/mL in People with Type 1 Diabetes on Basal–Bolus Insulin: Phase 4 OPTIMIZE Study Abstract Introduction OPTIMIZE evaluated the efficacy, safety and treatment satisfaction of insulin glargine 300 U/mL once daily (Gla-300 OD) in people with type 1 diabetes mellitus (T1DM) previously uncontrolled on basal insulin twice daily (BID) as part of basal–bolus therapy. Methods OPTIMIZE was a 28-week, prospective, interventional, single-arm phase 4 trial in adults with T1DM. At baseline, basal insulin BID treatment was switched to Gla-300 OD titrated to a fasting self-monitored blood glucose target of 4.4–7.2 mmol/L (80–130 mg/dL). The primary endpoint was the mean glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary endpoints included self-monitored blood glucose, fasting-plasma glucose, hypoglycaemia and patient-reported outcomes including the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs). Results Switching to Gla-300 OD significantly improved mean HbA1c (8.54% at baseline and 8.27% at week 24 [last observation carried forward, N = 94, p < 0.0001]; mean difference 0.27% [95% CI 0.15, 0.40]). There was a statistically significant decrease in fasting self-monitored blood glucose during the study (analysis of variance for repeated measures, p = 0.014; N = 72). Eight-point self-monitored blood glucose was significantly improved between baseline and week 24 for post-breakfast (p = 0.009), post-dinner (p = 0.009) and bedtime (p = 0.049) values. The study did not allow for any significant effects on confirmed and/or severe hypoglycaemia at the ≤ 3.9 mmol/L [≤ 70 mg/dL] or < 3.0 mmol/L [< 54 mg/dL] blood glucose cut-offs to be observed. Statistically significant improvements were observed in DTSQs total scores from baseline (24.1) to week 24 (29.4, p < 0.0001). Conclusions A basal–bolus regimen including Gla-300 OD was associated with improvements in HbA1c and treatment satisfaction in people with uncontrolled T1DM previously receiving basal–bolus insulin including a basal insulin BID analogue. Trial Registration EudraCT number: 2015-001186-46.

A Multinational Real-World Study on the Clinical Characteristics of Patients with Type 2 Diabetes Initiating Dapagliflozin in Southern Europe Abstract Introduction A real-world study was performed to describe the clinical characteristics of patients who received dapagliflozin to better understand differences when initiating dapagliflozin in various countries and different prescribing settings. Methods We assessed pooled data from observational studies carried out in Italy (n = 2484), Spain (n = 564) and Greece (n = 87). The primary objective was to compare the clinical profile of patients initiating dapagliflozin in the three countries. We also evaluated the percentage of patients who received dapagliflozin in clinical practice who satisfied DECLARE-TIMI 58 enrolment criteria. Results In Italy and Spain, around 90% of patients were receiving metformin vs. 66% in Greece (p < 0.0001). Patients in Greece had lower levels of estimated glomerular filtration rate and lower prevalence rates of retinopathy, prior stroke, acute myocardial infarction, peripheral arterial disease and atherosclerotic cardiovascular disease. Grouping the cohorts by prescribing setting (primary vs. specialist care), baseline HbA1c was lower in primary care (8.4 ± 1.7 vs. 8.7 ± 1.5, respectively; p < 0.0001). Significantly more patients were receiving other medications for concomitant conditions in specialist care. A total of 1416 patients (48%) did not meet DECLARE inclusion criteria, while 1561 (52%) patients met the criteria (Greece 41.05%, Italy 53.19%, Spain 51.35%). Conclusions Significant differences were seen among patients initiating dapagliflozin in southern Europe. Our results suggest that dapagliflozin was being initiated at different stages of the disease according to the country and prescribing settings. Such geographic heterogeneity may have an impact upon effectiveness of dapagliflozin on glucose lowering, as well as cardiovascular and renal outcomes.