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Tim Heise, Sascha Heckermann, J Hans DeVries
The variability in the time-action profiles of insulin preparations, in particular basal insulins, has been a matter of debate ever since the publication of a glucose clamp study comparing the day-to-day variability of three different basal insulins (glargine U100, detemir and NPH) in 2004 [1]. While critics did not contest the findings of a lower variability of some basal insulins in this and a later [2] glucose clamp study, they did question the relevance of a lower pharmacokinetic (PK) and pharmacodynamic (PD) variability for clinical endpoints [3, 4]...
May 17, 2018: Diabetes, Obesity & Metabolism
Tim Heise, Kadriye Kaplan, Hanne L Haahr
BACKGROUND: Insulin degludec (IDeg) has significantly lower day-to-day and within-day variability compared to insulin glargine (IGlar) 100U/mL (U100) and 300U/mL (U300). Here, we report post hoc assessments to confirm the robustness of these observations while accounting for potential experimental confounders. METHODS: Two euglycemic clamp studies in type 1 diabetes patients, comparing IDeg to IGlar-U100 (Study A, parallel design, 54 patients; Study B, crossover, 22 patients) and one study comparing IDeg to IGlar-U300 (Study C, crossover, 57 patients), all dosed at 0...
March 2018: Journal of Diabetes Science and Technology
Barbara Bohn, Peter Bramlage, Christian Wagner, Matthias Kaltheuner, Reinhard Welp, Stefan Sziegoleit, Artur Zimmermann, Hans Martin Reuter, Michael Hummel, Jörg Gloyer, Reinhard W Holl, Thomas Danne
BACKGROUND: Glargine U300 (Gla-300) is a further development of glargine U100 (Gla-100). Since 2015, Gla-300 has been available in Germany and Austria. We compared patients initiating therapy with Gla-300 with patients starting with Gla-100. Moreover, it was investigated whether patients from real-life diabetes care differ from patients participating in the EDITION clinical study program. METHODS: Data are based on the diabetes registries DPV and DIVE. Patients started/switched to Gla-100 or Gla-300 in 2015 were included...
August 21, 2017: Wiener Medizinische Wochenschrift
Hiroyuki Iuchi, Masaya Sakamoto, Daisuke Matsutani, Hirofumi Suzuki, Ryuzo Horiuchi, Kazunori Utsunomiya
BACKGROUND: Not only within-day glycemic variability but also day-to-day glycemic variability is a risk factor for diabetic patients. However, the ways of controlling day-to-day glycemic variability are unclear. We hypothesized that the durability of basal insulin plays an important role in controlling day-to-day glycemic variability in type 2 diabetes patients, and we therefore aimed to evaluate whether glargine U300, which exhibits prolonged absorption compared with glargine U100 but the same composition as glargine U100, would lead to improved day-to-day glycemic variability...
August 2017: Diabetes Technology & Therapeutics
Marina Gradišer, Maja Cigrovski Berković, Ines Bilić-Ćurčić
We included diabetes type 1 (T1DM) patients with suboptimal glycemic control on morning application glargine (I-Glar) U100, switching them to U300. After six months improvement in HbA1c was observed, while hypoglycemic episodes decreased. Switch from I-Glar U100 to U300 could be a good therapeutic option for that subset of patients.
July 2017: Diabetes Research and Clinical Practice
Tim Heise, Marianne Nørskov, Leszek Nosek, Kadriye Kaplan, Susanne Famulla, Hanne L Haahr
AIM: To compare day-to-day and within-day variability in glucose-lowering effect between insulin degludec (IDeg) and insulin glargine 300 U/mL (IGlar-U300) in type 1 diabetes. MATERIALS AND METHODS: In this double-blind, crossover study, patients were randomly assigned to 0.4 U/kg of IDeg or IGlar-U300 once daily for two treatment periods lasting 12 days each. Pharmacodynamic variables were assessed at steady-state from the glucose infusion rate profiles of three 24-hour euglycaemic glucose clamps (days 6, 9 and 12) during each treatment period...
July 2017: Diabetes, Obesity & Metabolism
Andreas Pfützner
In this issue, Pohlmeier et al report on a device assessment study in insulin-naïve patients with type 2 diabetes, to investigate the ease of use/learning and patient preference of the new prefilled U300 insulin glargine injection pen. Human factor studies are required by regulatory agencies and should ensure the proper use of the device in the context of the provided instructions. The patients found the device easy to learn/use and had a stable treatment satisfaction despite introduction of injection treatment...
March 2017: Journal of Diabetes Science and Technology
Marc Evans, Barrie Chubb, Jens Gundgaard
INTRODUCTION: To estimate the cost-effectiveness of insulin degludec (IDeg) versus insulin glargine U100 (IGlar U100) and new-to-market basal insulin analogues in patients with diabetes in order to aid decision-making in a complex basal insulin market. METHODS: A simple, short-term model was used to evaluate the costs and effects of treatment with IDeg versus IGlar U100 over a 12-month period in patients with type 1 (T1DM) and type 2 diabetes (T2DM) from the perspective of the UK National Health Service...
April 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Kathryn M Hurren, Jessica L O'Neill
Glargine 300 units/ml (Gla-300) is a novel basal insulin formulation approved in 2015 for the treatment of diabetes. This more concentrated form of glargine causes delayed redissolution from the subcutaneous depot after injection and thus altered action profile. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of Gla-300 in patients with type 1 diabetes mellitus (T1DM) will be reviewed. Expert opinion: Gla-300 has a flatter and more prolonged pharmacokinetic profile compared to glargine 100 units/ml (Gla-100), but is less potent on a unit per unit basis...
December 2016: Expert Opinion on Drug Metabolism & Toxicology
Tim Heise, Chantal Mathieu
Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine...
January 2017: Diabetes, Obesity & Metabolism
Alexandra Shields, Sailesh Sankaranarayanan
An active 28-year-old man with type 1 diabetes mellitus reported a reduced number of hypoglycaemic episodes following change in basal regime insulin glargine from U100 Lantus to U300 Toujeo. Consequently, an improved quality of life was also reported. Flash-based glucose monitoring was utilised to record 24-hour continuous glucose levels throughout two comparable 60-day periods before and after the change in regimen. Low blood glucose was most likely between 03:00 and 08:00. Nocturnal hypoglycaemic episodes (≤3...
June 15, 2016: BMJ Case Reports
Elizabeth M Lamos, Lisa M Younk, Stephen N Davis
INTRODUCTION: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. AREAS COVERED: This review highlights the published reports of the pharmacokinetic (PK) and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market...
2016: Therapeutics and Clinical Risk Management
L Monnier, D R Owens, G B Bolli
No abstract text is available yet for this article.
April 2016: Diabetes & Metabolism
Jennifer Goldman, John R White
OBJECTIVE: To describe the studies evaluating the efficacy and safety of new insulin glargine 300 U/mL (Gla-300) as a basal insulin in the treatment of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. DATA SOURCES: A literature search of MEDLINE was conducted (January 2008-June 2015) using the terms U300, Gla-300, and insulin glargine 300 units/mL and supplemented with congress abstracts published in 2014 and 2015. STUDY SELECTION AND DATA EXTRACTION: All English language studies assessing the efficacy and/or safety of Gla-300 were evaluated...
October 2015: Annals of Pharmacotherapy
Sanjay Kalra
Over the past few decades, continuous progress has been made in the development of insulin therapy. Basal insulins were developed around 60 years ago. However, existing basal insulins were found to have limitations. An ideal basal insulin should have the following properties viz. longer duration of action, a flat time-action profile, low day-to-day glycaemic variability, and the potential for flexible dosing. Basal insulins have advanced over the years, from lectin and neutral protamine Hagedorn to the currently available insulin degludec...
April 2015: Indian Journal of Endocrinology and Metabolism
Gemma Sutton, Joan Minguet, Carmen Ferrero, Peter Bramlage
INTRODUCTION: Insulin glargine (100 U/ml; U100) was the first long-acting basal insulin analog to be introduced into clinical practice and it remains the most widely used. Although U100 is an effective and safe treatment, research is ongoing to optimize the time-action profile. The focus of this review is insulin glargine [rDNA origin] injection 300 U/ml (U300), a novel formulation that contains a higher concentration of insulin than U100. AREAS COVERED: The clinical efficacy and safety of U300 in patients with type 1 and type 2 diabetes mellitus are discussed, with an emphasis on recently released data from the Phase III EDITION clinical trials...
December 2014: Expert Opinion on Biological Therapy
Jordi Mesa
Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now...
July 20, 2015: Medicina Clínica
Maria Ida Maiorino, Michela Petrizzo, Annalisa Capuano, Dario Giugliano, Katherine Esposito
INTRODUCTION: The basal insulin products currently on market do not optimally mimic endogenous insulin secretion. These unmet clinical needs have fueled the development of new basal insulin analogues for improving their pharmacokinetics/pharmacodynamics profile. AREAS COVERED: We review the recent literature investigating the efficacy and safety of new basal insulin analogues in type 2 diabetes, as in the USA, insulin utilization accounted for 26% of treatment visits for these patients in 2012...
June 2014: Expert Opinion on Biological Therapy
David R Owens, Glenn Matfin, Louis Monnier
Insulin remains the most effective and consistent means of controlling blood glucose levels in diabetes. Since 1946, neutral protamine Hagedorn (NPH) has been the predominant basal insulin in clinical use. However, absorption is variable due to the need for resuspension and the time-action profile (peak activity 4-6 h after subcutaneous administration) confers an increased propensity for between-meal and nocturnal hypoglycaemia. In the 1980s, recombinant DNA technology enabled modifications to the insulin molecule resulting in the soluble long-acting insulin analogues, glargine and detemir...
February 2014: Diabetes/metabolism Research and Reviews
A A Szewczak, L Ortoleva-Donnelly, M V Zivarts, A K Oyelere, A V Kazantsev, S A Strobel
Key to understanding the structural biology of catalytic RNA is determining the underlying networks of interactions that stabilize RNA folding, substrate binding, and catalysis. Here we demonstrate the existence and functional importance of a Hoogsteen base triple (U300.A97-U277), which anchors the substrate helix recognition surface within the Tetrahymena group I ribozyme active site. Nucleotide analog interference suppression analysis of the interacting functional groups shows that the U300.A97-U277 triple forms part of a network of hydrogen bonds that connect the P3 helix, the J8/7 strand, and the P1 substrate helix...
September 28, 1999: Proceedings of the National Academy of Sciences of the United States of America
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