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https://www.readbyqxmd.com/read/27905149/scope-limitations-of-fmoc-chemistry-spps-based-approaches-to-the-total-synthesis-of-insulin-lispro-via-ester-insulin
#1
Stephen Kent, Balamurugan Dhayalan, Kalyaneswar Mandal, Nischay Rege, Michael Weiss, Simon Eitel, Thomas Meier, Ralph Schoenleber
We have systematically explored three approaches based on Fmoc chemistry SPPS for the total chemical synthesis of the key depsipeptide intermediate for the efficient total chemical synthesis of insulin. The approaches used were: stepwise Fmoc chemistry SPPS; the 'hybrid method', in which maximally-protected peptide segments made by Fmoc chemistry SPPS are condensed in solution; and, native chemical ligation using peptide-thioester segments generated by Fmoc chemistry SPPS. A key building block in all three approaches was a Glu[Oβ(Thr)] ester-linked dipeptide equipped with a set of orthogonal protecting groups compatible with Fmoc chemistry SPPS...
November 30, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27860499/premixed-insulin-analogue-compared-with-basal-plus-regimen-for-inpatient-glycemic-control
#2
Abraham Edgar Gracia-Ramos, María Del Pilar Cruz-Domínguez, Eduardo Osiris Madrigal-Santillán, José Antonio Morales-González, Eduardo Madrigal-Bujaidar, José Leopoldo Aguilar-Faisal
BACKGROUND: No previous studies have investigated the use of a premixed insulin analogue in a hospital setting. OBJECTIVE: To compare the efficacy and safety of treatment with premixed insulin analogue (insulin lispro mix 75/25, LM75/25) with the basal-plus regimen with insulin glargine in hospitalized patients with type 2 diabetes (T2D). MATERIALS AND METHODS: A randomized clinical trial in hospitalized patients with T2D and glucose >140 mg/dL on admission was performed...
November 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27776251/the-effects-of-exenatide-twice-daily-compared-to-insulin-lispro-added-to-basal-insulin-in-latin-american-patients-with-type-2-diabetes-a-retrospective-analysis-of-the-4b-trial
#3
Silvia Beatriz Gorban de Lapertosa, Gustavo Frechtel, Elise Hardy, Leobardo Sauque-Reyna
AIMS: Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. METHODS: This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin...
October 8, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27660663/insulin-lispro-low-mixture-twice-daily-vs-basal-insulin-glargine-once-daily-and-prandial-insulin-lispro-once-daily-as-insulin-intensification-strategies-in-patients-with-type-2-diabetes-latin-american-subpopulation-analysis-of-a-randomized-trial
#4
Arturo Rojas, Georgina Sposetti, Jorge L Gross, Douglas Eugenio Barbieri, Ran Duan, Bruno Linetzky, Janaina Martins De Lana, Oded Stempa, Angel Rodriguez
BACKGROUND: This post hoc analysis examined the efficacy and safety of twice-daily insulin lispro low mixture (LM25) and once-daily basal insulin glargine plus once-daily prandial insulin lispro (IGL) in a Latin American subpopulation with type 2 diabetes mellitus (T2DM). METHODS: A phase 4, randomized, open-label, parallel-arm trial included participants aged 18-75 years with T2DM taking once-daily insulin glargine and stable doses of metformin and/or pioglitazone with glycated hemoglobin (HbA1c) 7...
2016: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/27563254/comparison-of-efficacy-and-safety-of-two-starting-insulin-regimens-in-non-asian-asian-indian-and-east-asian-patients-with-type-2-diabetes-a-post-hoc-analysis-of-the-paradigm-study
#5
Linong Ji, Kyung Wan Min, Juliana Oliveira, Thomas Lew, Ran Duan
OBJECTIVE: The objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L) in insulin-naïve patients with type 2 diabetes from different racial/ethnic groups. METHODS: Three subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89). RESULTS: All subgroups recorded glycated hemoglobin (HbA1c) reductions: non-Asian (LM25, -2...
2016: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/27553192/an-assessment-of-the-central-disposition-of-intranasally-administered-insulin-lispro-in-the-cerebrospinal-fluid-of-healthy-volunteers-and-beagle-dogs
#6
Stephen Lowe, Emanuele Sher, Graham Wishart, Kimberley Jackson, Eunice Yuen, Claire Brittain, Siew Chinn Fong, David O Clarke, William H Landschulz
Intranasally administered regular insulin and insulin aspart have shown cognitive benefit for patients with Alzheimer's disease (AD). To support development of intranasally administered insulin analogs for AD, the central disposition of intranasal insulin lispro in the cerebrospinal fluid (CSF) of healthy volunteers was investigated. Healthy volunteers (N = 8) received two sequential doses of intranasal insulin lispro (48 or 80 IU followed by 160 IU) by Aero Pump in an open-label, single-period study with serial CSF and serum sampling over 5 hours after each dose...
August 23, 2016: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/27540462/treatment-with-insulin-analogs-especially-glargine-and-lispro-associates-with-better-renal-function-and-higher-hemoglobin-levels-in-type-1-diabetic-patients-with-impaired-kidney-function
#7
Christoph Hasslacher, Felix Kulozik, Justo Lorenzo Bermejo
OBJECTIVES: The influence of type of insulin treatment - insulin analogs versus human insulin - on the development of diabetes related vascular complications has been sparsely investigated. We examine here possible differences regarding kidney function and hemoglobin levels. METHODS: Multiple linear regression was used to investigate the relationship between the following characteristics measured in 509 type 1 diabetic patients who were recruited in an outpatient practice: current clinical status and treatment modalities, type of injected insulin and the routine laboratory parameters hemoglobin, HbA1c, serum creatinine, eGFR, hs CRP and urinary albumin/creatinine ratio...
August 2016: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27528391/addition-of-20-kda-peg-to-insulin-lispro-alters-absorption-and-decreases-clearance-in-animals
#8
Mary Pat Knadler, Tri-Hung Nguyen, Kristina Campanale, Michael J De Veer, John M Beals, Shun Li, Ryan Hansen, Angela Siesky, M Dodson Michael, Christopher J H Porter
PURPOSE: Determine the pharmacokinetics of insulin peglispro (BIL) in 5/6-nephrectomized rats and study the absorption in lymph duct cannulated (LDC) sheep. METHODS: BIL is insulin lispro modified with 20-kDa linear PEG at lysine B28 increasing the hydrodynamic size to 4-fold larger than insulin lispro. Pharmacokinetics of BIL and insulin lispro after IV administration were compared in 5/6-nephrectomized and sham rats. BIL was administered IV or SC into the interdigital space of the hind leg, and peripheral lymph and/or serum samples were collected from both LDC and non-LDC sheep to determine pharmacokinetics and absorption route of BIL...
December 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27517679/clinical-effects-and-safety-of-direct-acting-insulin-analogs-in-patients-with-type-1-diabetes-a-nation-wide-observational-cohort-study
#9
Vincent Lak, Ann-Marie Svensson, Mervete Miftaraj, Stefan Franzén, Björn Eliasson
INTRODUCTION: Studies comparing direct-acting insulin analogs (DAIs) in terms of effectiveness and long-term safety are scarce. Our aim was to explore these variables in clinical practice among patients with type 1 diabetes, including the elderly and those with renal impairment. METHODS: We linked four national registers in a population-based cohort study. Patients with type 1 diabetes and continuous use of all currently available DAIs (lispro, aspart, or glulisine) in 2005-2013 were monitored for up to 7...
September 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27411698/insulin-injection-into-lipohypertrophic-tissue-blunted-and-more-variable-insulin-absorption-and-action-and-impaired-postprandial-glucose-control
#10
Susanne Famulla, Ulrike Hövelmann, Annelie Fischer, Hans-Veit Coester, Lidia Hermanski, Matthias Kaltheuner, Lars Kaltheuner, Lutz Heinemann, Tim Heise, Laurence Hirsch
OBJECTIVE: Lipohypertrophy (LHT) is common in insulin-treated patients but its exact impact on insulin absorption and action is unclear. RESEARCH DESIGN AND METHODS: In this crossover study, 13 patients with type 1 diabetes received subcutaneous abdominal injections of 0.15 units/kg insulin lispro into LHT (confirmed by examination and ultrasound) and normal adipose tissue (NAT). On one day, a euglycemic clamp was performed with two injections each into LHT and NAT, and on another day one injection per region was given before a standardized mixed meal (75 g carbohydrates), all in randomized order...
September 2016: Diabetes Care
https://www.readbyqxmd.com/read/27393697/a-randomized-clinical-trial-comparing-basal-insulin-peglispro-and-insulin-glargine-in-combination-with-prandial-insulin-lispro-in-patients-with-type-1-diabetes-imagine-1
#11
(no author information available yet)
This article will be part of a supplement and will be republished when the entire issue is complete.
July 8, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27390032/20-years-of-insulin-lispro-in-pediatric-type-1-diabetes-a-review-of-available-evidence
#12
Kevin Kaiserman, Heike Jung, Imane Benabbad, Beate Karges, Michel Polak, Myriam Rosilio
BACKGROUND: Insulin lispro, the first rapid-acting insulin analog, was developed 20 years ago and has been studied in multiple situations and various populations. OBJECTIVE: To review the literature on the use of insulin lispro in children, adolescents, and young adults. PATIENTS: Children, adolescents, and young adults with type-1-diabetes. METHODS: One hundred and twenty-two relevant publications, identified by a systematic (MEDLINE) and manual literature search, were reviewed...
July 8, 2016: Pediatric Diabetes
https://www.readbyqxmd.com/read/27371341/comparison-of-insulin-lispro-mix-25-with-insulin-lispro-mix-50-as-insulin-starter-in-chinese-patients-with-type-2-diabetes-mellitus-classify-study-a-subgroup-analysis-of-a-phase-4-open-label-randomized-trial
#13
Qing Su, Chao Liu, Hongting Zheng, Jun Zhu, Peng Fei Li, Lei Qian, Wen Ying Yang
BACKGROUND: Premixed insulins are recommended starter insulins in Chinese patients after oral antihyperglycemic medication (OAM) failure. Here, we compared the efficacy and safety of Insulin Lispro Mix25 (LM25) twice daily (BID) and Insulin Lispro Mix50 (LM50) BID as starter insulin regimen in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with OAMs. METHODS: Primary efficacy outcome in this open-label, parallel, randomized clinical trial was change in hemoglobin A1c (HbA1c) from baseline to 26 weeks...
July 1, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27356188/the-cost-effectiveness-of-exenatide-twice-daily-bid-versus-insulin-lispro-three-times-daily-tid-as-add-on-therapy-to-titrated-insulin-glargine-in-patients-with-type-2-diabetes
#14
J Gordon, P McEwan, U Sabale, B Kartman, B H R Wolffenbuttel
OBJECTIVE: To evaluate the cost-effectiveness of exenatide twice daily (BID) versus bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is suboptimal with titrated basal insulin glargine and metformin. METHODS: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study...
June 29, 2016: Journal of Medical Economics
https://www.readbyqxmd.com/read/27333446/improving-efficacy-of-inhaled-technosphere-insulin-afrezza-by-postmeal-dosing-in-silico-clinical-trial-with-the-university-of-virginia-padova-type-1-diabetes-simulator
#15
Roberto Visentin, Clemens Giegerich, Robert Jäger, Raphael Dahmen, Anders Boss, Marshall Grant, Chiara Dalla Man, Claudio Cobelli, Thomas Klabunde
BACKGROUND: Technosphere(®) insulin (TI), an inhaled human insulin with a fast onset of action, provides a novel option for the control of prandial glucose. We used the University of Virginia (UVA)/Padova simulator to explore in-silico the potential benefit of different dosing regimens on postprandial glucose (PPG) control to support the design of further clinical trials. Tested dosing regimens included at-meal or postmeal dosing, or dosing before and after a meal (split dosing). METHODS: Various dosing regimens of TI were compared among one another and to insulin lispro in 100 virtual type-1 patients...
September 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27279266/continuous-glucose-monitoring-in-patients-with-type-2-diabetes-treated-with-glucagon-like-peptide-1-receptor-agonist-dulaglutide-in-combination-with-prandial-insulin-lispro-an-award-4-substudy
#16
Johan Jendle, Marcia A Testa, Sherry Martin, Honghua Jiang, Zvonko Milicevic
AIM: To conduct a substudy, using 24-hour continuous glucose monitoring (CGM), of the AWARD-4 trial, which was designed to compare insulin + glucagon-like peptide-1 receptor agonist treatment with an insulin-only regimen. METHODS: The AWARD-4 trial randomized 884 conventional insulin regimen-treated patients to dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM substudy included 144 patients inserted with a Medtronic CGMS iPro CGM device to enable 3-day glucose monitoring...
October 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27267431/lispro-administered-by-the-qs-m-needle-free-jet-injector-generates-an-earlier-insulin-exposure
#17
Jinbo Hu, Hui Shi, Changhong Zhao, Xiyue Li, Yue Wang, Qingfeng Cheng, Richa Goswami, Qianna Zhen, Mei Mei, Ying Song, Shumin Yang, Qifu Li
OBJECTIVE: The aim of this study is to evaluate the pharmacokinetic and pharmacodynamic (PK-PD) profiles of lispro administered by the QS-M needle-free jet injector in Chinese subjects. RESEARCH DESIGN AND METHODS: A randomized, double-blind, double-dummy, cross-over study was performed. Eighteen healthy volunteers were recruited. Lispro (0.2 units/kg) was administered by the QS-M needle-free jet injector or by conventional pen. Seven-hour euglycemic clamp tests were performed...
September 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27265390/randomized-double-blind-clinical-trial-comparing-basal-insulin-peglispro-and-insulin-glargine-in-combination-with-prandial-insulin-lispro-in-patients-with-type-1-diabetes-imagine-3
#18
R M Bergenstal, H Lunt, E Franek, F Travert, J Mou, Y Qu, C J Antalis, M L Hartman, M Rosilio, S J Jacober, E J Bastyr
AIMS: To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes. MATERIALS AND METHODS: In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management...
November 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27234693/randomized-double-blind-clinical-trial-comparing-basal-insulin-peglispro-and-insulin-glargine-in-combination-with-prandial-insulin-lispro-in-patients-with-type-2-diabetes-imagine-4
#19
T Blevins, T R Pieber, G Colón Vega, S Zhang, E J Bastyr, A M Chang
AIMS: To evaluate the efficacy and safety of basal insulin peglispro (BIL) with those of insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (T2D). METHODS: In this phase III, multicentre, double-blind, 26-week study, we randomized patients with T2D [glycated haemoglobin (HbA1c) ≥7 and <12%, on ≥1 insulin injections daily) to BIL (n = 691) or glargine (n = 678), in combination with lispro. RESULTS: At week 26, the primary objective of non-inferiority of BIL versus glargine for HbA1c reduction was achieved (least squares mean difference -0...
November 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27228041/what-is-the-role-of-concentrated-insulin-in-diabetes-management
#20
Cortney M Mospan
Two concentrated analog insulins, long-acting insulin glargine U-300 (Toujeo) and rapid-acting insulin lispro (Humalog U-200), were recently approved by the FDA. Providers must be aware of clinical differences in these new product formulations compared with their nonconcentrated formulations, so that they can select appropriate patients for these products and minimize drug errors.
June 2016: JAAPA: Official Journal of the American Academy of Physician Assistants
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