Indian consensus on durability of glycemic control in type 2 diabetes management and role of oral antidiabetic drugs

The prevalence of type 2 diabetes mellitus (T2DM) is increasing in an alarming way in India as well as across the globe. In order to minimize complications, there is a need to maintain good glycemic control in patients with T2DM and long-term durable glycemic control remains a challenge. Clinically, this challenge was addressed by step-wise intensification of therapy with additional antidiabetic drugs to maintain glycemic control. Various disease and patient-related factors as well as different antidiabetic agents influenced the durability of glycemic control differently. While understanding of the factors that influenced therapeutic outcomes had evolved, there was paucity of information about the durability of glycemic control and the role of oral antidiabetic drugs (OADs) in achieving it. With an objective to understand the role of durability of glycemic response in the management of Indian patients with T2DM, 4 advisory board meetings attended by 48 physicians from across the country were conducted in Mumbai, Delhi, Kolkata and Bengaluru. There was consensus to consider durability of glycemic control as an important goal in the management of T2DM. Personalized approach in T2DM management along with early initiation of dual combination therapy were recommended to achieve durability. Age group of patients, body mass index, glycated hemoglobin levels at diagnosis, presence or absence of comorbidities and complications are important factors that need to be considered before initiating dual combination therapy for patients with T2DM.

Cost-Effectiveness of Oral Antidiabetic Drugs: A Prospective Multicenter Study of Real-World Patients

This real-world, multicenter, prospective study aims to analyze the cost-effectiveness of prevalent oral antidiabetic drugs, including traditional Chinese medicine and its compounds, used in China. Type 2 diabetes patients initiated on one or several of the most prevalent antidiabetic drugs were recruited on the baseline and followed up over one year with no restriction on drug discontinuation, switching, and add-on. Different drugs were evaluated on their efficacy, adverse effect (AE), health-related quality of life (HRQoL), and cost. Treatments were defined as the intent-to-treat in the primary analysis and on-treatment in the sensitivity analyses. A rich set of patients’ baseline characteristics was collected and controlled using the multivariate linear model in the primary analysis and inverse probability weighting and double selection—a machine learning algorithm—in the sensitivity analyses. Estimates of “raw” outcomes, which are not adjusted by covariates and calculated as subgroup means, show that the use of Xiaoke Pill alone and in combination is among the most effective therapies with 50% and 54% of patients reaching the control target of HbA1c < 6.5%. In terms of cost, Xiaoke Pill and gliclazide, which cost participants 4,350 and 5,150 RMB per year on average, are among the least costly therapies. After adjusting patient characteristics, monotherapy and combination therapy using the Xiaoke Pill again display the best control rates, of 45% and 43% against 33% of metformin. Regarding cost, the Xiaoke Pill costs a patient 5,340 RMB per year, in sharp contrast with 8,550 RMB for metformin and 10,330 RMB for acarbose. Our study suggests that the use of Xiaoke Pill—alone or in combination—is associated with better glycemic control and lower cost than some allopathic medications such as metformin or acarbose and shows a similar incidence of hypoglycemia.

Dipeptidyl Peptidase-4 Inhibitor Administration Is Associated with Higher Eosinophil Counts and Batter Clinical Outcomes in Patients with Aorta Intramural Hematoma

Objectives Investigating whether dipeptidyl peptidase-4 (DPP-4) inhibitors could influence clinical outcomes in intramural hematoma (IMH) patients with diabetes mellitus (DM). Methods IMH patients who received a "wait and watch strategy" were included. Cox proportional hazard models were constructed to identify potential risk factors. A Kaplan–Meier survival analysis was used to estimate all-cause and aorta-related mortality during the follow-up period. Results From January 2000 to December 2020, 1094 IMH patients were divided into group A (n=572, IMH patients without DM), group B (n=191, IMH patients with DM and receiving oral antidiabetic drugs [without admission of DDP-4 inhibitors]) and group C (n=331, IMH patients with DM and receiving oral antidiabetic drugs [including admission of DDP-4 inhibitors]). Group C had the lowest rate of aorta-related adverse events (6.4%), aorta-related mortality (1.2%) and reintervention (5.2%). Cox proportional hazard models revealed that lower eosinophil count (per 0.1, hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.51-0.73, P< 0.001) and thicker hematoma thickness (HR, 1.22; 95% CI, 1.06-1.39, P <0.001) were associated with higher occurrences of aorta-related adverse events. Lower eosinophil count (per 0.1, HR, 0.24; 95% CI, 0.15-0.40, P <0.001), larger descending aorta diameters (HR, 1.12; 95% CI, 1.02-1.23, P <0.021), and thicker hematoma thickness (HR, 3.25; 95% CI, 2.36-4.46, P <0.001) were also associated with increased aorta-related mortality. Kaplan-Meier survival analysis revealed a significant decrease in all-cause and aorta-related mortality in group C ( P <0.001). Conclusions DPP-4 administration influences progression of IMH patients with DM, leading to a lower rate of aorta-related adverse events, aorta-related mortality, and reinterventions.

Update of pancreas transplantation. Experience of the Hospital Doce de Octubre

Pancreas transplantation (PT) is considered as the only treatment that can convert a diabetic patient in a euglucemic state without the use of insulin or oral antidiabetic drugs. From 1996 to the end of 2016, more than 50,000 PT were performed in USA, and in Spain were performed 1.730 PT during the last 10 years. In this review we will perform an update of PT considering the introduction of several advances in the last years, adding our accumulated experience from the beginning of our program in the year 1995. The first PT was carried out in the Hospital of the University of Minnesota, and from that date several significant improvements have been introduced along the time due to advances in surgical technique in pancreas donors and recipients, perioperative management of patients, and introduction of more potent immunosuppressors able to reduce the rejection rate under 20%. Although PT is a therapy associated with a higher morbidity (pancreas graft thrombosis, systemic and intraabdominal infections, anastomotic leakages, etc.), currently most of the PT teams have obtained a rate of 93% of patient survival at 3-years, and between 78% and 83% of graft survival at 3-years. Additionally, the normal pancreas graft function is associated with an improvement of quality of life and most of complications related to diabetes, without the necessity to treat with antidiabetics drugs or insulin.

Liu Wei Di Huang Wan and the Delay of Insulin Use in Patients with Type 2 Diabetes in Taiwan: A Nationwide Study

Introduction. Patients with type 2 diabetes are widely prescribed metformin for controlling blood glucose levels to avoid related comorbidities. In Taiwan, traditional Chinese medicine (TCM) is also commonly used, especially Liu Wei Di Huang Wan (LWDHW), which has been reported to delay the occurrence of kidney failure. However, the effect of combinational therapy of TCM and oral antidiabetic drugs is still unclear. This study aims to estimate their efficacy in delaying insulin use. Materials and Methods. This case-control study was conducted using one million randomized samples from the National Health Insurance Research Database in Taiwan. The effects of TCM and LWDHW were estimated using the Cox proportional hazards model. Results. In this study, 70,036 diabetic patients were enrolled; of them, 17,451 (24.9%) used insulin, while the rest (52,585, 75.1%) did not. TCM users had a lower risk for insulin use (HR: 0.58, 95% CI: 0.56–0.60). LWDHW users had a lower risk compared with patients who used other TCM (HR: 0.86, 95% CI: 0.82–0.90) and presented a dose-dependent effect. Conclusion. The use of LWDHW and oral antidiabetic drugs is highly associated with the delay in the use of insulin. Clinical practitioners may take them into consideration when treating patients with type 2 diabetes.

Possible Synergistic Antidiabetic Effects of Quantified Artemisia judaica Extract and Glyburide in Streptozotocin-Induced Diabetic Rats via Restoration of PPAR-α mRNA Expression

Several members of the genus Artemisia are used in both Western and African traditional medicine for the control of diabetes. A considerable number of diabetic patients switch to using oral antidiabetic drugs in combination with certain herbs instead of using oral antidiabetic drugs alone. This study examined the effect of Artemisia judaica extract (AJE) on the antidiabetic activity of glyburide (GLB) in streptozotocin (STZ)-induced diabetes. Forty-two male Wistar rats were divided into seven equal groups. Normal rats of the first group were treated with the vehicle. The diabetic rats in the second–fifth groups received vehicle, GLB (5 mg/kg), AJE low dose (250 mg/kg), and AJE high dose (500 mg/kg), respectively. Groups sixth–seventh were treated with combinations of GLB plus the lower dose of AJE and GLB plus the higher dose of AJE, respectively. All administrations were done orally for eight weeks. Fasting blood glucose (FBG) and insulin levels, glycated hemoglobin (HbA1c) percentage, serum lipid profile, and biomarkers of oxidative stress were estimated. The histopathological examination of the pancreas and the immunohistochemical analysis of anti-insulin, anti-glucagon, and anti-somatostatin protein expressions were also performed. The analysis of the hepatic mRNA expression of PPAR-α and Nrf2 genes were performed using quantitative RT-PCR. All treatments significantly lowered FBG levels when compared with the STZ-control group with the highest percentage reduction exhibited by the GLB plus AJE high dose combination. This combination highly improved insulin levels, HbA1c, and lipid profile in blood of diabetic rats compared to GLB monotherapy. In addition, all medicaments restored insulin content in the β-cells and diminished the levels of glucagon and somatostatin of the α- and δ-endocrine cells in the pancreatic islets. Furthermore, the GLB plus AJE high dose combination was the most successful in restoring PPAR-α and Nrf2 mRNA expression in the liver. In conclusion, these data indicate that the GLB plus AJE high dose combination gives greater glycemic improvement in male Wistar rats than GLB monotherapy.

MARKET OF ORAL ANTIDIABETIC DRUGS IN THE REPUBLIC OF CRIMEA

Diabetes mellitus is one of the most significant social problems of public health. The main pathogenetic factors in the development of type 2 diabetes mellitus are a decrease in insulin synthesis by β­cells of Langerhans islets or impaired insulin receptor sensitivity to insulin, which leads to a high risk of insulin resistance and β­cell dysfunction.