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Background: To assess the bioequivalence between Gan & Lee (GL) glargine U300 and Toujeo® regarding pharmacokinetics (PK), pharmacodynamics (PD), and safety in Chinese healthy male participants. Methods: A single-center, randomized, double-blind, single-dose, two-preparation, two-sequence, four-cycle repeated crossover design study was performed to compare GL glargine U300 and Toujeo® in 40 healthy participants. The primary PK endpoints were the area under the curve of glargine metabolites, M1 concentration from 0 to 24 hours (AUC0-24h), and the maximum glargine concentration within 24 hours post-dose (Cmax). The primary PD endpoints were the area under the glucose infusion rate (GIR) curve from 0 to 24 hours (AUCGIR.0-24h) and the maximum GIR within 24 hours post-dose (GIRmax). Results: GL Glargine U300 demonstrated comparable PK parameters (AUC0-24h, Cmax, AUC0-12h, and AUC12-24h of M1) and PD responses [AUCGIR.0--24h, GIRmax, AUCGIR.0-12h, and AUCGIR.12--24h] to those of Toujeo®, as indicated by 90% confidence intervals ranging from 80% to 125%. No significant disparities in safety profiles were observed between the two treatment groups, and there were no reported instances of serious adverse events. Conclusion: The PK, PD, and safety of GL glargine U300 were bioequivalent to that of Toujeo®. [ABSTRACT FROM AUTHOR]

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Copyright of Remedia is the property of Medical Tribune CZ, s.r.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To evaluate the cost-utility of insulin degludec (IDeg) versus insulin glargine U100 (IGlar U100) and insulin glargine U300 (IGlar U300) in Chinese patients with type 2 diabetes. Methods From the perspective of health system, based on the IQVIA CORE diabetes model, the long-term medical costs and health outcomes of treatment with IDeg, IGlar U100 and IGlar U300 were calculated and an incremental cost-effectiveness analysis was performed. Health outcomes included life years and quality adjusted life year (QALY), and medical costs included drug cost, disease management cost and complication treatment cost. The price of insulin adopted the price of national volume-based procurement. The simulation model runs for 30 years at a discount rate of 5%. The robustness of the results was evaluated by one-way sensitivity analysis and probabilistic sensitivity analysis. Results Compared with the IGlar U100 group, the quality of life in IDeg group was gained by 0.060 QALY, the direct medical cost was increased by RMB 158 Yuan, and the ICER was RMB 2 639 Yuan/QALY. Compared with the IGlar U300 group, the quality of life in IDeg group was gained by 0.085 QALY, the direct medical cost was reduced by RMB 1 402 Yuan. Sensitivity analysis verified the robustness of the results. Conclusions Compared with IGlar U100 and IGlar U300, IDeg was likely to be a cost-effective treatment in Chinese patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: There is an ongoing discussion about possible differences between insulin degludec (IDeg-100) and glargine U300 (IGlar-300). There is little data and head-to-head comparison of IDeg-100 and IGlar-300 regarding their simultaneous impact on glycemic variability and oxidative stress in patients with type 2 diabetes mellitus (T2DM). Objective: In our randomized, open-label, crossover study, we compared the impact of IDeg-100 and IGlar-300 on glycemic variability and oxidative stress in insulin-naive patients with T2DM. Methods: We recruited a total of 25 adult patients with T2DM (7 females) whose diabetes was uncontrolled (HbA1c ≥7.5%) on two or more oral glucose-lowering drugs; a total of 22 completed the study. Mean age was 57.3 (SD 6.99) years and duration of diabetes was 9.94 (SD 5.01) years. After the washout period, they were randomized alternately to first receive either IDeg-100 or IGlar-300 along with metformin. Each insulin was administered for 12 weeks and then switched. At the beginning and end of each phase, biochemical and oxidative stress parameters were analyzed. On 3 consecutive days prior to each control point, patients performed a 7-point self-monitoring of blood glucose profile. Oxidative stress was assessed by measuring thiol groups and hydroperoxides (determination of reactive oxygen metabolites test) in serum. Results: IGlar-300 reduced mean glucose by 0.02-0.13 mmol/L, and IDeg-100 reduced glucose by 0.10-0.16 mmol/L, with no significant difference. The reduction of the coefficient of glucose variation also did not show a statistically significant difference. IGlar-300 increased thiols by 0.08 μmol/L and IDeg-100 increased thiols by 0.15 μmol/L, with no significant difference (P=.07) between them. IGlar-300 reduced hydroperoxides by 0.040 CARR U and IDeg-100 increased hydroperoxides by 0.034 CARR U, but the difference was not significant (P=.12). Conclusions: The results of our study do not show a significant difference regarding glycemic variability between patients receiving either insulin IDeg-100 or IGlar-300, although IGlar-300 showed greater dispersion of data. No significant difference in oxidative stress was observed. In a larger study, doses of insulins should be higher to achieve significant impact on glycemic parameters and consequently on glycemic variability and oxidative stress. [ABSTRACT FROM AUTHOR]

With the availability of second-generation basal insulin analogs, insulin degludec (100 and 200 units/ml [degludec]) and insulin glargine 300 units/ml (glargine U300), clinicians now have long-acting, efficacious treatment options with stable pharmacokinetic profiles and associated low risks of hypoglycemia that may be desirable for many patients with type 2 diabetes. In this narrative review, we summarize the current evidence on glycemic control in hospitalized patients and review the pharmacokinetic properties of degludec and glargine U300 in relation to the challenges these may pose during the hospitalization of patients with type 2 diabetes who are receiving outpatient regimens involving these newer insulins. Their increased use in clinical practice requires that hospital healthcare professionals (HCPs) have appropriate protocols to transfer patients from these second-generation insulins to formulary insulin on admission, and ensure the safe discharge of patients and transition back to degludec or glargine U300. However, there is no guidance available on this. Based on the authors' clinical experience, we identify key issues to consider when arranging hospital care of such patients. We also summarize the limited available evidence on the potential utility of these second-generation basal insulin analogs in the non-critical inpatient setting and identify avenues for future research. To address current knowledge gaps, it is important that HCPs are educated about the differences between standard formulary insulins and second-generation insulins, and the importance of clear communication during patient transitions. [ABSTRACT FROM AUTHOR]

Insulin degludec is a new ultra-long-action basal insulin. Using treat-to-target protocols, controlled trials have shown comparable HbA 1c reductions with insulin degludec and comparators in both type 1 and type 2 diabetes. Most studies identify, however, better control of fasting plasma glucose with insulin degludec vs. either insulin glargine U100 or detemir, and all have consistently demonstrated clinically relevant decreases in (nocturnal) hypoglycaemic episodes. These characteristics have provided added therapeutic value for insulin degludec in clinical practice. Thus, the aim of this review is to discuss, within the context of randomized and observational studies, the clinical effects of insulin degludec use in type 1 and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Research on pharmacological therapies for the treatment and prevention of Coronavirus Disease 2019 (COVID-19) is limited in patients with Type 2 Diabetes Mellitus (T2DM). In this case, diabetes management of a 51-year-old male patient who was followed up and treated with COVID-19 diagnosis in the pandemic clinic is presented. While metformin (2000 mg/day) oral therapy was continued, insulin glargine U100 (IGlar100) was added to the treatment subcutaneously. In addition, enoxaparin, hydroxychloroquine, azithromycin were started to be administered to the patient. During follow-up, respiratory distress and tachypnea (26 breaths/min), high fever (38.3°C), increased CRP (42 mg/dL), and decreased oxygen saturation (91%) were detected. Favipiravir was added to the treatment, and metformin was stopped due to possible lactic acidosis risk. IGlar300 treatment with more potency effect and lower risk of hypoglycaemia was initiated while IGlar100 was discontinued. In the follow-ups, titration was provided with IGlar300 to keep fasting blood glucose between 100-140 mg/dL and postprandial one between 140-180 mg/dL. In the treatment for this purpose, a maximum of 34 units/day insulin was needed. Capillary blood sugar monitoring was revised every 12 hours and then once a day. As the infection was brought under control, the required dose of IGlar300 decreased to 14 units/day. After diabetes training with a video phonecall, he was discharged with metformin and IGlar300. IGlar300 may be effective against diabetes in the COVID-19 pandemic. In addition, a significant contribution can be made both to the treatment safety of the patient in a glycemic sense and to the safety of contamination by reduced contact of health care professionals. [ABSTRACT FROM AUTHOR]

Aims: To investigate efficacy, safety and usability of the GlucoTab system for glycaemic management using insulin glargine U300 in non‐critically ill hospitalized patients with type 2 diabetes (T2D). Materials and Methods: In this open, non‐controlled single‐arm pilot study, glycaemic control at the general ward of a tertiary care hospital was guided by a mobile decision support system (GlucoTab) for basal‐bolus insulin dosing using the novel basal insulin analogue insulin glargine U300 for the first time. Glycaemic control was surveilled with capillary glucose measurements and continuous glucose monitoring (CGM). The primary endpoint was efficacy of glycaemic management, defined as the percentage of blood glucose measurements within the target range of 3.9 to 7.8 mmol/L. Results: A total of 30 patients with T2D (12 female; age, 67 ± 11 years; HbA1c, 70 ± 26 mmol/mol; BMI, 31.8 ± 5.6 kg/m2; length of study, 8.5 ± 4.5 days) were included. In total, 894 capillary glucose values and 49 846 data points of CGM were available, of which 56.1% of all measured capillary glucose values and 54.3% of CGM values were within the target area (3.9‐7.8 mmol/L). Overall capillary mean glucose was 8.5 ± 1.2 and 8.4 ± 1.2 mmol/L assessed by CGM. Time within glucose target improved continuously during the course of treatment, while time within hypoglycaemia (<3.9 mmol/L) decreased substantially. The GlucoTab‐suggested total daily dose was accepted by staff in 97.3% of situations. Conclusions: Treatment with GlucoTab using insulin glargine U300 in hospitalized patients with T2D is effective and safe. [ABSTRACT FROM AUTHOR]

Introduction: Administered basal insulin markedly influences the fasting plasma glucose (FPG) level of individuals with type 1 diabetes. Insulin degludec (IDeg) and insulin glargine U300 (IGlar U300) are now available as ultra-long-acting insulin formulations, but whether or how their glucose-stabilizing effects differ remains unclear. We will compare the effects of these basal insulins on parameters related to blood glucose control, with a focus on day-to-day glycemic variability, in individuals with type 1 diabetes treated with multiple daily injections.Methods: A multicenter, randomized, open-label, crossover, comparative study (Kobe Best Basal Insulin Study 2) will be performed at 13 participating institutions in Japan. A total of 46 C-peptide-negative adult outpatients with type 1 diabetes will be randomly assigned 1:1 by a centralized allocation process to IGlar U300 (first period)/IDeg (second period) or IDeg (first period)/IGlar U300 (second period) groups, in which subjects will be treated with the corresponding basal insulin for consecutive 4-week periods. The basal insulin will be titrated to achieve an FPG of less than 130 mg/dL initially and then less than 110 mg/dL if feasible. In the last week of each period, plasma glucose will be determined seven times a day by self-monitoring of blood glucose (SMBG) and intraday and day-to-day glucose excursions will be determined by flash glucose monitoring (FGM). The primary end point is comparison of day-to-day glycemic variability as evaluated by the standard deviation (SD) of FPG during the last week of each treatment period. Secondary end points include the coefficient of variance of FPG, the frequency of severe hypoglycemia as evaluated by SMBG, the duration of hypoglycemia as evaluated by FGM, intraday glycemic variability calculated from both SMBG and FGM data, and the administered insulin dose.Planned Outcomes: The results of the study will be submitted for publication in a peer-reviewed journal to report differences in the effects of two ultra-long-acting basal insulins, IDeg and IGlar U300.Conclusion: This head-to-head comparison will be the first study to compare the effects of IDeg and IGlar U300 on day-to-day FPG variability in C-peptide-negative individuals with type 1 diabetes.Trial Registration: Registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry as 000029630 on 20 June 2017.Funding: Novo Nordisk Pharma Ltd. [ABSTRACT FROM AUTHOR]

Insulin is a peptide hormone released by pancreatic beta cells. An autoimmune reaction in diabetes mellitus type 1 causes the beta cells to die, preventing insulin from being produced or released into the bloodstream; that impacts 30 million people globally and is linked to shortened lifespan due to acute and chronic repercussions. Insulin therapy aims to replicate normal pancreatic insulin secretion, which includes low levels of insulin that are always present to support basic metabolism, as well as the two-phase secretion of additional insulin in response to high blood sugar - an initial spike in secreted insulin, followed by an extended period of continued insulin secretion. This is performed by combining various insulin formulations at varying rates and lengths of time. Since the beginning of human insulin use, several advances in insulin formulations have been made to help meet these aims as much as possible, resulting in improved glycaemic control while limiting hypoglycemia. In this review, we looked at devices used by patients with type 1 diabetes, such as insulin pumps, continuous glucose monitors, and, more recently, systems that combine a pump with a monitor for algorithm-driven insulin administration automation. We intend to provide insight into supplementary therapies and nanotechnology employed in insulin therapy as a result of our review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Type 1 diabetes is characterized by insulin deficiency and requires near-physiological insulin replacement. In most patients, this is accomplished by basal bolus therapy consisting of a long-acting basal insulin administered once or twice daily and short-acting insulin with main meals. Several long-acting insulin analogs have been developed to optimize basal insulin therapy., Areas Covered: This paper reviews the design of - and data from - randomized controlled trials (RCTs) to assess glucose lowering efficacy and safety of long-acting insulin analogs for the treatment of type 1 diabetes., Expert Opinion: Due to the non-inferiority treat-to-target design of insulin, RCTs treatment differences primarily appear as differences in hypoglycemia risk. Data suggest that the first generation long-acting insulin analogs insulin glargine U100 and insulin detemir have a similar glucose lowering efficacy compared to NPH insulin but a lower risk of hypoglycemia, particularly during nighttime. The newer analogs insulin glargine U300 and insulin degludec provide non-inferior efficacy, although insulin glargine U300 is less potent unit-to-unit. Insulin degludec reduces hypoglycemia risk compared to insulin glargine U100. Future studies should explore the potential for further improvement of treatment results in type 1 diabetes by a structured approach to personalization of basal insulin therapy.

Introduction: We aimed to see whether insulin glargine U300 can provide better blood glucose control while reducing hypoglycaemia in a more homogeneous population compared to previous studies., Material and Methods: The retrospective study included type 1 diabetes mellitus (T1DM) patients with frequent hypoglycaemia. For evaluation of fasting blood glucose, haemoglobin glycated (HbA 1c ) and weight at 6 months and 12 months (final), observation windows of 120-240 days (4-8 months) and 240-480 days (9-16 months) after insulin glargine U300 initiation, respectively, were permitted. Mean follow-up time was 12 months. Hypoglycaemia was defined as blood glucose level < 70 mg/dl, either symptomatic or asymptomatic, measured in hospital or at home., Results: Forty-four patients were included in the study, and 35 patients completed the study - 20 (57.1%) females and 15 (42.9%) males, with a mean age of 24.1 ±6.6 years. Mean body mass index was 24.4 ±7.4 kg/m 2 . A significant decrease was not found between baseline and HbA 1c values at 6 months ( p = 0.199), but a significant decrease was found in the final period (between 9-16 months) ( p = 0.025). Hypoglycaemic events occurred in all patients (100%) before using insulin glargine U300, while the incidence of hypoglycaemic events gradually decreased to 74.3%, 68.6%, and 68.6% between months 1-3, 3-6, and 6-9, respectively. Of the 26 patients who declared their level of satisfaction, 23 (88.5%) were satisfied, 2 (7.7%) indicated that there was no significant difference, and 1 (3.8%) patient was unsatisfied., Conclusions: Over 9-16 months of follow-up, insulin glargine U300 led to a significant reduction not only of HbA 1c levels but also of the frequency of hypoglycaemia, and also yielded high satisfaction rates., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2021 Termedia & Banach.)

To examine the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) or once-daily second-generation basal insulin analogs (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes in routine clinical practice. A 12-week multicenter, open-label, randomized, pilot study was performed in 52 subjects with type 2 diabetes treated with oral antidiabetic drugs (OADs). Subjects were randomized to once-daily IDegAsp (n = 26) or basal insulin (n = 26). The primary endpoint was percent change in HbA1c from baseline to week 12. Furthermore, it was analyzed post hoc in subgroups stratified by baseline HbA1c. During a follow-up period, percent change in HbA1c was not significantly different between the two groups (p = 0.161). Daily insulin doses and frequency of overall hypoglycemia were also similar in the two groups. In post hoc analyses, once-daily basal insulin was more effective than IDegAsp in subjects with HbA1c more than or equal to 8.5% (p < 0.05); however, in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant improvement in percent change in HbA1c at week 12, compared with basal insulin (p < 0.01). Although there was no apparent difference in the HbA1c-lowering effects between two groups, when compared in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant effect in comparison with once-daily basal insulin. These findings suggest that the baseline HbA1c level might provide the important information for choosing IDegAsp or basal insulin in patients insufficiently controlled with OADs. This trial was registered with UMIN (no. UMIN000035431).

Type 2 diabetes is a chronic, progressive disease with increasing prevalence and still late diagnostic. This leads to an increase in the incidence of chronic complications, with signifi cantly increasing health costs. There is also a delay in the onset of insulin therapy in patients with type 2 diabetes for causes related to both patients and physicians. Despite advances in treatment, a low proportion of patients achieve adequate glycemic control. The high hypoglycemia prevalence, consequence of insulin, has led to the development of a new generation long-acting basal insulins to achieve a more stable and prolonged action profile, reducing the variability and risk of hypoglycemia. The EDITION program evaluated the efficacy and safety of glargine U300 compared to glargine U100 in patients with type 1 and 2 diabetes at different stages of the disease. Gla-300 is a new formulation of insulin glargine which has a more stable and prolonged pharmacokinetic and pharmacodynamic profile. Gla-300 demonstrated efficacy and tolerability comparable to glargine U100, with a significant decrease in the risk of hypoglycemia, at night and in 24 hours, providing greater flexibility in the injection schedule, with a window of 6 hours. No increase in weight was observed compared to glargine U100. Bright study (2018) compared glargine U300 vs. degludec U100, demonstrating greater benefit in relation to the risk of hypoglycemia with Gla-300 during titration period. Gla-300 is a last-generation basal insulin, available to improve metabolic control, with a lower risk of hypoglycemia.

Objective: To review clinical efficacy and safety of insulin glargine 300 units/mL (Gla-300), a novel high-concentration basal insulin. Data Sources: A MEDLINE search was performed to identify relevant articles published 1960 through February 2015 using the search term glargine 300. Published abstracts from conference proceedings of the American Diabetes Association 74th Scientific Sessions were identified. Study Selection and Data Extraction: Human studies that evaluated pharmacokinetics, efficacy, or safety of Gla-300 were included. Data Synthesis: Six trials investigated efficacy and safety of Gla-300; 3 of 6 trials were available in abstract form only. The EDITION group of trials compared Gla-300 to insulin glargine 100 units/mL (Gla-100) in several populations. These included subjects with type 1 diabetes continuing mealtime insulin and subjects with type 2 diabetes on basal and mealtime insulin, basal insulin and oral antidiabetic drugs (OADs), and with no prior insulin use. Three studies were multinational including 2 studies exclusive to Japanese participants. Each clinical trial was an open-label, multicenter, randomized study with 6 to 12 months of follow-up. Gla-300 demonstrated similar reductions in HbA 1c compared to Gla-100. Basal insulin requirements increased by 11% to 17% with Gla-300 without excessive weight gain. Rates of overall hypoglycemia were similar with Gla-300 compared to Gla-100; however, 16% to 38% less nocturnal hypoglycemia was observed in type 2 clinical trials. Conclusions: Gla-300 in combination with mealtime insulin or OADs has shown comparable glycemic control with higher insulin dose requirements versus Gla-100, and may induce less hypoglycemia in patients with type 2 diabetes., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2015.)