Preparation and in vitro/in vivo evaluation of a novel shape-memory gastric retentive delivery system loaded with Gliclazide (GLZ) for type 2 diabetes mellitus therapy

Objective:Peripheral arterial disease (PAD), an established marker of premature death and cardiovascular risk in general, is highly prevalent. We analysed factors associated with poor outcomes in an observational cohort, with particular focus on the effect of guideline orientation in the management of these patients.Methods:PACE-PAD is a multicentre, prospective, observational study of PAD patients in primary care. PAD guideline orientation was stated, if patients received the following: exercise training, (if applicable) advice for smoking cessation and diet, therapy for diabetes mellitus, hypertension, hypercholesterolaemia, or antiplatelets/anticoagulants. Multivariate regression models were applied to assess factors associated with all cause death, cardiovascular/cerebrovascular death, or cardiovascular/cerebrovascular/peripheral vascular non-fatal events.Results:After an 18-month follow-up, of the 5099 PAD patients analysed (mean age 68.0 ± 9.0 years, 68.5% males), only 28.4% of patients met all applicable quality indicators for guideline-oriented treatment. However, most patients were to a large extent managed in line with guidelines. While exercise training was reported in 41.8%, rates were very high for smoking cessation (90.7%), therapy for hypertension (92.5%), diabetes mellitus (82.0%), hypercholesterolemia (83.3%) and antiplatelet therapy (86.7%). Regarding events, there were inhomogeneous results with a statistically significant higher rate of cardiovascular/cerebrovascular deaths and all-cause deaths, but a lower rate of non-fatal vascular events in patients treated according to guidelines compared to those who were not. Limitations of this study include the open, non-controlled design, possible patient selection bias and misclassification of events.Conclusion:Even if the guideline orientation for the various indicators was remarkably stable across the three follow-up visits, the rate of patients comprehensively treated according to the guidelines was relatively low, which calls for optimisation. There was a lack of differentiation between the guideline-oriented and non-guideline-oriented therapy in terms of outcomes, which may be due to patient-related or other factors, and warrants further research.

Gliclazide MR in the structure of antihyperglycemic therapy according to the data of Moscow region diabetes register

Injectable thermosensitive hydrogel-based sustained delivery system for anti-diabetic peptides in type 2 diabetes mellitus therapy: A review.

Diabetes mellitus (DM) has a millennia-long history, with early references dating back to ancient Egypt and India. However, it was not until the 20th century that the connection between diabetes and insulin was fully understood. The sequencing of insulin in the 1950s initiated the convergence of biotechnology and diabetes management, leading to the development of recombinant human insulin in 1982. This marked the start of peptide-based therapies in DM. Recombinant peptides for DM treatment: Numerous recombinant peptides have been developed since, starting with modified insulin molecules, with the aim of bettering DM management through fine-tuning the glycemic response to insulin. Peptide-based therapies in DM have expanded substantially beyond insulin to include agonists of Glucagon-like peptide-1 receptor and Glucose-dependent insulinotropic polypeptide receptor, glucagon receptor antagonists, and even peptides exerting multiple receptor agonist effects, for better metabolic control. Insulin pumps, continuous glucose monitoring, and automated insulin delivery systems: The development of modern delivery systems combined with real-time glucose monitoring has significantly advanced diabetes care. Insulin pumps evolved from early large devices to modern sensor-augmented pumps with automated shutoff features and hybrid closed-loop systems, requiring minimal user input. The second-generation systems have demonstrated superior outcomes, proving highly effective in diabetes management. Islet cell transplantation, organoids, and biological pancreas augmentation represent innovative approaches to diabetes management. Islet cell transplantation aims to restore insulin production by transplanting donor beta cells, though challenges persist regarding graft survival and the need for immunosuppression. Organoids are a promising platform for generating insulin-producing cells, although far from clinical use. Biological pancreas augmentation relies on therapies that promote beta-cell (re)generation, reduce stress, and induce immune tolerance. Further biotechnology-driven perspectives in DM will include metabolic control via biotechnology-enabled tools such as custom-designed insulin hybrid molecules, machine-learning algorithms to control peptide release, and engineering cells for optimal peptide production and secretion.

Eco-friendly chitosan-based nanostructures in diabetes mellitus therapy: Promising bioplatforms with versatile therapeutic perspectives

AimsPatients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM.Methods and resultsOptimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n= 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7%, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used.ConclusionIn patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel.Clinical trial identifier: www.clinicaltrials.gov—NCT00642174

Background Diabetes mellitus (DM) is a degenerative disease and a leading global cause of death, often linked to increased oxidative stress and free radicals. Prolonged DM can lead to various complications, including kidney issues, heart problems, vision impairment, and more. Dietary regulation is a recommended approach to managing DM. GEMAR beverage powder, derived from germinated black rice and mung bean, holds the potential as a source of antioxidants and is beneficial for individuals with DM due to its rich phytochemical content. Objective This study aims to determine the yield and antioxidant activity of GEMAR powder beverage as a therapy for DM. Methods This is a quantitative research study employing a true experimental design, which will be analyzed descriptively. The ingredients GEMAR beverage powder germinated black rice, germinated mung bean, tempeh, red spinach, skimmed milk, soy protein isolate, and maltodextrin. The GEMAR beverage powder production includes sorting, mixing, roasting, drying, milling, and filtration stages. The GEMAR beverage yield value was obtained by comparing the final powder weight and the initial powder weight. Analysis of the antioxidant activity of GEMAR beverage powder using the DPPH method. Results The yield of GEMAR beverage powder was 41,6% and the antioxidant activity of GEMAR powder beverage was 24,30±0,07%. Conclusion This study concluded that GEMAR beverage powder is a functional beverage that has antioxidant activity and has the potential to be used as a therapy for DM. Keywords: antioxidants; functional beverages; black rice; diabetes mellitus.

Potentially inappropriate prescribing (IP) for elderly medical inpatients in Taiwan: A hospital-based study

Antihypertensive therapy in diabetes mellitus: insights from ALLHAT and the Blood Pressure-Lowering Treatment Trialists’ Collaboration meta-analysis

Preface

The aim of the study was to evaluate the clinical safety and efficacy of hydroxychloroquine in subjects with were poorly controlled type 2 diabetes mellitus (T2DM), despite treatment with insulin glargine and a combination of gliclazide and metformin. 105 patients with type 2 DM, mean age 56.84 years and mean body mass index (BMI) 26.30 kg/m 2 , were enrolled in this multicentre open label trial. They were given hydroxychloroquine 400 mg/day in addition to previous treatment with insulin glargine (≥30 units a day), gliclazide (80 mg a day) and metformin (1000 mg a day) for a period of six months. Hydroxychloroquine 400 mg/day, when added to insulin glargine and the combination of gliclazide and metformin, significantly decreased hemoglobin A1c (HbA1c) at six months from a mean of 8.15±0.24 to a mean of 6.69±0.42 (p<0.0001) and fasting plasma glucose (FPG) at six months from a mean of 209.5 ± 31.23 mg/dl to 115.14 ± 36.94 mg/dl and post prandial plasma glucose (PPG) from a mean of 338.22 ± 31.76 mg/dl to 147.71 ±22.47 mg/dl (p<0.0001). Hydroxychloroquine was well tolerated throughout the study period. The mean dose of insulin glargine decreased during the study from 35.51 ± 9.93 units per day to 20.00 ± 9.6 units/day at six months (p<0.0001). The frequency of insulin glargine injections decreased from a mean of 2.15 ± 0.22/day to 1.18 ± 0.85/day (p<0.0001). In 43 (41%) patients insulin glargine had to be totally stopped. In 13 (12%) patients the dose of gliclazide decreased to 40 mg. Hydroxychloroquine was found to improve glycemic control, when given as a fourth drug (quadruple drug therapy) in addition to insulin and the combination of gliclazide and metformin in patients with type 2 DM. In a significant number of patients, insulin therapy could be stopped, and in the rest the dose of insulin and gliclazide could be reduced.

Objective To compare the effect of gliclazide modified-release combined with morn ing or evening taking metformin to glycosylated hemoglobin A1 c (HbA1 c)and homeostasis model assessment(HOMA-IR and HOMA-β)on patients with newly diagnosed type 2 diabetes mellitus and its safety.Methods This 12-week study included 60 newly diagnosed type 2 diabetic patients who were randomly divided into two groups.Based on diet controlling and exercise therapy,patients in group A received gliclazide modified-release (diamicron) 60 mg (2 tablets) once daily before breakfast and metformin (glucophage) 850 mg(1 tablet) once daily after breakfast; patients in group B received gliclazide modifiedrelease tablet (diamicron) 60 mg (2 tablets) once daily before breakfast and metformin (glucophage) 850 mg (1 tablet) once daily after supper.Fasting blood glucose (FBG),Postprandial 2 h plasma glucose (2 h PG),Fasting insulin (F-ins),Postprandial 2 h insulin (P-ins),HbA1 c,Body weight,liver and kidney functions,triglyceride (TG),total cholesterol (TC),electrocardiogram (ECG),adverse drug reactions were measured and recorded.Results Glycosylated henoglobin A1c (HbA1c) in group A and B decreased (0.93 ± 0.63) ％ and (0.99 ± 0.89) ％,respectively,there was no significant differences between the two groups (P ＞ 0.05),HOMA-IR decreased 0.52 ± 0.62 in group A and 0.34 ± 0.59 in group B,there was no significant difference between the two groups (P ＞ 0.05).HOMA-βincreased (13.59 ± 12.83) ％ in group A and (11.35 ± 15.40) ％ in group B,there was no significant difference between the two groups (P ＞ 0.05).Conclusions Combination of gliclazide modified-release and metformin could decrease HbA1c,improve insulin resistence and increase β-cell function effectively,there is no significantly difference in morning or evening taking metformin. Key words: Type 2 diabetes mellitus; Chronotherapy ; Gliclazide modified-release ; Metformin

Diabetes mellitus and the associated complications are metabolic diseases with high morbidity that result in poor quality of health and life. The lack of diagnostic methods for early detection results in patients losing the best treatment opportunity. Oral hypoglycemics and exogenous insulin replenishment are currently the most common therapeutic strategies, which only yield temporary glycemic control rather than curing the disease and its complications. Exosomes are nanoparticles containing bioactive molecules reflecting individual physiological status, regulating metabolism, and repairing damaged tissues. They function as biomarkers of diabetes mellitus and diabetic complications. Considering that exosomes are bioactive molecules, can be obtained from body fluid, and have cell-type specificity, in this review, we highlight the multifold effects of exosomes in the pathology and therapy of diabetes mellitus and diabetic complications.

The prevalence of morbid obesity and its sequelae is increasing in Germany, Europe and worldwide. Bariatric surgery is thus gaining in importance for the treatment of patients with malignant obesity. Creation of a gastric bypass is one of the most frequently performed procedures for obesity. The gastric bypass has been used -since 1966 as a surgical means of weight reduction in obese patients. In the mean time various modifications have been developed. Thus, for example, the laparoscopic procedure represents the current standard. After the operation most patients experience an excess weight loss (EWL) of between 61 and 83 %. The comorbidities of obesity are also markedly improved and in a high percentage even cured after the operation. It is worthy of note that diabetes mellitus type II improves shortly after the operation even before any weight loss has occurred. The suggests that the operation induces more than "just" a loss of weight. For decades the gastric bypass has been a well known standard operation of overweight and, in addition to the reduction in weight, is also a therapy for diabetes mellitus -type II.

Objective To evaluate the current state of glycemie control in Chinese patients with type 2 diabetes mellitus who have received oral antidiabetic agents in the out-patient clinic,and the efficacy and safety of optimized regiments of gliclazide modified-release tablets (Diamicron MR, SERVIER, Tianjin) in patients with failed glycemic control (HbA1c 6.5%). Methods The patients with type 2 diabetes were enrolled from 54 hospitals in more than 20 cities and received long-term (more than 3 months) oral antidiabetic agents. HbA1c was measured and the success rate of HbA1c reduction was evaluated. The patients who failed to achieve glycemic control (HbA1c 6. 5%) and received daily multiple-dosing insulin secretagogues were provided with the optimized treatment regimen, consisting of replacing daily multiple-dosing insulin secretagogues with single-dosing gliclazide sustained-release tablets. Clinical efficacy and safety were evaluated after three months treatment. Results The survey of glycemic control revealed that the mean HbA1c of 5 586 patients with diabetes mellitus was (7.97±2.89)% ,and the success rate (HbA1c≤6.5%) was 14. 1%. Further more, HbA1c decreased from (8.23±4.00)% before optimization to (6.86±2.24)% after optimization with the average decrement of 1.37% (P<0. 001) and the success rate was raised to 34. 1%. The gliclazide modified-release tablets were well tolerated by most patients, only 2.6% of whom were reported to experience unconfirmed hypoglycemia. Conclusion The success rate of glycemic control was low in Chinese out-patients with type 2 diabetes mellitus receiving oral antidiabetic agents in the clinic. The optimized regimen of gliclazide modified-release tablets taken once daily can down-regulate glycemic levels and increase the success rate of HbA1c reduction,and thus plays efficiently and safely a key role in the optimized management of type 2 diabetes mellitus. Key words: Diabetes mellitus,type 2; Optimized once daily treatment regimen; HbA1c; Efficacy; Safety