Insulin glargine: the first clinically useful extended-acting insulin in half a century?

Abstract:

:Insulin glargine (HOE 901) appears to be the first clinically useful extended-acting insulin preparation for 50 years. A combination of a di-arginine addition to the C-terminal of the insulin B-chain, and a glycine substitution in the A-chain, produce an insulin which is soluble at acid pH, but precipitates in sc. tissue at neutral pH after injection. This new insulin analogue has slightly lower receptor binding affinity compared to human insulin, but equal potency in vivo. Prolonged receptor binding is not found, and IGF-1 binding is not significantly different from human insulin. Glucose clamp and sc. disappearance studies confirm that insulin glargine has a much slower onset of effect than NPH (Neutral Protamine Hagedorn) insulin, and a much more protracted profile of action. Variability of absorption is difficult to assess from published studies, but is not dissimilar to NPH insulin. Patient studies in Type 1 and Type 2 diabetes published to date are inconclusive, but appear to confirm differences in pharmacokinetics between insulin glargine and NPH, with significantly lower fasting plasma glucose levels or reduction in night hypoglycaemia. No safety concerns have emerged. It thus appears that insulin glargine is a genuinely new addition to the insulin family, and with further clinical experience it may well be possible to achieve better basal blood glucose control (without enhanced risk of hypoglycaemia), particularly at night or in conjunction with rapid-acting insulin analogues.

authors

Home P

doi

10.1517/13543784.8.3.307

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

307-14

issue

3

eissn

1354-3784

issn

1744-7658

journal_volume

8

pub_type

杂志文章
  • Next generation of mammalian target of rapamycin inhibitors for the treatment of cancer.

    abstract:INTRODUCTION:Because of the central role of the mammalian target of rapamycin (mTOR) pathway in the control and distribution of signals essential for mRNA translation of mitogenic genes and generation of oncogenic proteins, effective targeting of mTOR remains a major goal in medical oncology. AREAS COVERED:This articl...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2013.787066

    authors: Nelson V,Altman JK,Platanias LC

    更新日期:2013-06-01 00:00:00

  • Investigational therapies for celiac disease.

    abstract::Celiac disease is an autoimmune condition affecting genetically susceptible individuals. It is produced by the ingestion of gluten contained in wheat, rye, barley, and related products. The only treatment currently available is strict adherence to a gluten-free diet for life. This requirement for dietary compliance is...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780903369333

    authors: Rodrigo L

    更新日期:2009-12-01 00:00:00

  • Fertilisation Promoting Peptide: a key player in male fertility/subfertility?

    abstract::'Male factor' problems contribute to subfertility in a significant proportion of couples. In some instances, defective sperm production has qualitative and/or quantitative effects on the semen profile; in others, no obvious defects can be detected, yet spermatozoa are non-fertilising. Recent studies have revealed that...

    journal_title:Expert opinion on investigational drugs

    pub_type: 社论

    doi:10.1517/13543784.6.12.1797

    authors: Fraser LR

    更新日期:1997-12-01 00:00:00

  • Discontinued drugs in 2008: oncology drugs.

    abstract::The failure of drug candidates in clinical development remains a critical issue for the pharmaceutical and biotechnology industries. This article documents those oncology drugs discontinued in 2008 and briefly reviews reasons for termination of development. Source information was derived from a search of the Pharmapro...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543780903151806

    authors: Williams R

    更新日期:2009-11-01 00:00:00

  • Pharmacology of argatroban.

    abstract::Argatroban, a synthetic peptidomimetic antithrombin agent, is the first clinical anticoagulant solely to target thrombin. For some time, this drug has been used in Japan for the management of thromboembolic disorders. Recently, it has been approved in Japan for use in thrombotic and ischaemic stroke. Despite a large n...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.8.5.625

    authors: Jeske W,Walenga JM,Lewis BE,Fareed J

    更新日期:1999-05-01 00:00:00

  • American Association for Cancer Research: Clinical trials of immunotherapeutics and immunologic monitoring. April 1-5, 2000, San Francisco, CA, USA.

    abstract::A major session at this annual gathering of the cancer researchers from around the globe dealt with the current state of immunotherapy for cancer. Immunotherapy is a form of cancer treatment that enhances its scientific promise and legitimacy with each passing year. As a result, this topic has become one of the most h...

    journal_title:Expert opinion on investigational drugs

    pub_type:

    doi:10.1517/13543784.9.6.1413

    authors: Salgaller ML

    更新日期:2000-06-01 00:00:00

  • Novel metabotropic glutamate receptor 4 and glutamate receptor 8 therapeutics for the treatment of anxiety.

    abstract:INTRODUCTION:The fast actions of the excitatory neurotransmitter glutamate are mediated by glutamate-gated ion channels (ionotropic Glu receptors). Metabotropic glutamate receptors (mGlus) are coupled to second messenger pathways via G proteins and modulate glutamatergic and GABAergic neurotransmission. Of the eight di...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2014.986264

    authors: Raber J,Duvoisin RM

    更新日期:2015-04-01 00:00:00

  • Transgenic animals as drug factories: a new source of recombinant protein therapeutics.

    abstract::The utility of transgenic animal bioreactors for the production of complex therapeutic proteins is based on lower production costs, higher production capacities and safer, pathogen free products. Until gene therapy becomes broadly efficacious, transgenic-derived therapeutics are the most attractive alternative for pro...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.7.10.1683

    authors: Van Cott KE,Velander WH

    更新日期:1998-10-01 00:00:00

  • Recent progress in development of cyclin-dependent kinase 7 inhibitors for cancer therapy.

    abstract::Introduction: Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1080/13543784.2021.1850693

    authors: Liang H,Du J,Elhassan RM,Hou X,Fang H

    更新日期:2021-01-01 00:00:00

  • Effects of ADP-receptor antagonism beyond traditional inhibition of platelet aggregation.

    abstract::Atherothrombosis, or thrombus formation, at the site of a disrupted atherosclerotic plaque is the common pathophysiology related to myocardial infarction, ischaemic stroke and peripheral arterial disease. A growing body of evidence demonstrates an important role for vascular inflammation in the pathophysiology of athe...

    journal_title:Expert opinion on investigational drugs

    pub_type: 社论

    doi:10.1517/13543784.13.5.457

    authors: Herbert JM

    更新日期:2004-05-01 00:00:00

  • A consideration of PPAR-gamma ligands with respect to lipophilicity: current trends and perspectives.

    abstract::The fact that PPAR-gamma is expressed dramatically higher in fat, regulating gene transcription in response to small lipophilic ligands, supports an essential role of increased lipophilicity for those ligands. On the other hand, the skepticism concerning high lipophilicity as a characteristic associated with undesirab...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.16.4.413

    authors: Giaginis C,Theocharis S,Tsantili-Kakoulidou A

    更新日期:2007-04-01 00:00:00

  • Targeting enzymes to cancers--new developments.

    abstract::Two methods of using tumour located enzymes have been described. These are antibody directed enzyme prodrug therapy (ADEPT) and macromolecule directed enzyme prodrug therapy (MDEPT), where the tumour located enzyme converts a non-toxic prodrug into a cytotoxic drug at tumour sites. The alternative use of tumour locate...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.8.2.161

    authors: Bagshawe KD,Burke PJ,Knox RJ,Melton RG,Sharma SK

    更新日期:1999-02-01 00:00:00

  • Discontinued drugs in 2006: pulmonary-allergy, dermatological, gastrointestinal and arthritis drugs.

    abstract::This perspective is the second in a series discussing drugs dropped from development in 2006, with a focus on pulmonary-allergy, dermatological, gastrointestinal and arthritis drugs. A survey of discontinued drugs from 2006 is provided, based on data from the Pharmaprojects database, along with an analysis of biology,...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.16.9.1327

    authors: Ozdemir C,Akdis CA

    更新日期:2007-09-01 00:00:00

  • The potential role of PD0332991 (Palbociclib) in the treatment of multiple myeloma.

    abstract:INTRODUCTION:Multiple myeloma (MM) remains an incurable malignancy indicating a need for continued investigation of novel therapies. Recent studies have highlighted the role of cyclin-dependent kinases (CDK) in the pathogenesis of MM. PD0332991 (Palbociclib) is an orally bioavailable, highly selective inhibitor of the ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2015.993753

    authors: Altenburg JD,Farag SS

    更新日期:2015-02-01 00:00:00

  • Investigational antiviral therapies for the treatment of influenza.

    abstract:INTRODUCTION:Influenza viral ribonucleoprotein complexes (vRNPs) play a key role in viral transcription and replication; hence, the recent development of novel anti-influenza drugs targeting vRNPs has garnered widespread interest. AREAS COVERED:We discuss the function of the constituents of vRNPs and summarize those v...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2019.1606210

    authors: Yang J,Huang Y,Liu S

    更新日期:2019-05-01 00:00:00

  • Prospects for the introduction of targeted antioxidant drugs for the prevention and treatment of diseases related to free radical pathology.

    abstract:INTRODUCTION:Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target esse...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2019.1631284

    authors: Kontoghiorghes GJ,Kontoghiorghe CN

    更新日期:2019-07-01 00:00:00

  • Potential use of exenatide for the treatment of obesity.

    abstract:INTRODUCTION:Obesity is a major health threat in the Western world because of its high incidence and prevalence, and its association with metabolic and cardiovascular disease as well as cancer. The reduction of food intake in obese patients can be achieved only transiently (generally for no longer than 6 months), in th...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2011.630660

    authors: Folli F,Guardado Mendoza R

    更新日期:2011-12-01 00:00:00

  • Risperidone (Risperdal): clinical experience with a new antipsychosis drug.

    abstract::Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha- adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic effects. Early studies demonstrated risperidone to be an effective medication for psychoti...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章

    doi:10.1517/13543784.8.4.443

    authors: Keks NA,Culhane C

    更新日期:1999-04-01 00:00:00

  • Novel C5a regulators in inflammatory disease.

    abstract::Complement is part of the innate immune system, acting to protect the host from microorganisms such as bacteria, and other foreign and abnormal cells. Although primarily protective, complement activation can also cause damage to the host. In a number of inflammatory diseases, including rheumatoid arthritis and dermati...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.14.7.807

    authors: Mizuno M,Cole DS

    更新日期:2005-07-01 00:00:00

  • Therapeutic intervention for Alzheimer's disease with γ-secretase inhibitors: still a viable option?

    abstract:INTRODUCTION:Compounds that inhibit or modulate γ-secretase, the pivotal enzyme which generates β-amyloid (Aβ), are potential therapeutics for Alzheimer's disease (AD). AREAS COVERED:This article briefly reviews the profile of γ-secretase inhibitors that have reached the clinic and discusses the clinical issues surrou...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2011.550572

    authors: Imbimbo BP,Panza F,Frisardi V,Solfrizzi V,D'Onofrio G,Logroscino G,Seripa D,Pilotto A

    更新日期:2011-03-01 00:00:00

  • Investigational platelet-derived growth factor receptor kinase inhibitors in breast cancer therapy.

    abstract:INTRODUCTION:Aberrant regulation of platelet-derived growth factors (PDGFs) and their receptors (PDGFR) has been shown to be involved in many solid tumors, including breast cancer. PDGFR-α and PDGFR-β expressions were documented in breast cancer and are correlated with tumor aggressiveness and metastasis. Preclinical e...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2014.895323

    authors: Criscitiello C,Gelao L,Viale G,Esposito A,Curigliano G

    更新日期:2014-05-01 00:00:00

  • Triple-drug chemotherapy regimens in combination with an anti-EGFR agent in metastatic colorectal cancer - prospects from phase II clinical trials.

    abstract:INTRODUCTION:The addition of monoclonal antibody (mAb) epidermal growth factor receptor (EGFR) inhibitors to classic chemotherapy doublet backbones has improved survival of metastatic colorectal cancer (mCRC). However, the role of triple-drug chemotherapy regimens in combination with an anti-EGFR mAb inhibitor is not y...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2019.1599860

    authors: Matos I,Noguerido A,Ros J,Mulet N,Argilés G,Elez É,Tabernero J

    更新日期:2019-05-01 00:00:00

  • Targeted therapy and promising novel agents for the treatment of advanced soft tissue sarcomas.

    abstract:INTRODUCTION:Soft tissue sarcomas (STS) are a rare and difficult to treat malignancy. Efforts to utilize targeted therapy have been ongoing for the last decade and have resulted in the approval of pazopanib for treatment of advanced disease. Although several other agents have been investigated, the inability to predict...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2015.1076792

    authors: Mohindra N,Agulnik M

    更新日期:2015-01-01 00:00:00

  • Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury?

    abstract:INTRODUCTION:The ubiquitin-proteasome system (UPS) is responsible for the degradation of misfolded or damaged proteins, regulating inflammatory processes and cell cycle progression. The aim of this article is to summarize the currently available data regarding the possible utility of proteasome inhibitors (PIs) in the ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2013.840287

    authors: Kandilis AN,Karidis NP,Kouraklis G,Patsouris E,Vasileiou I,Theocharis S

    更新日期:2014-01-01 00:00:00

  • Custirsen (OGX-011): a second-generation antisense inhibitor of clusterin for the treatment of cancer.

    abstract:BACKGROUND:Clusterin is a stress-induced cytoprotective chaperone protein, regulated by HSF1, and functions similarly to a small heat-shock protein. Clusterin is expressed in a variety of cancers and associated with broad-spectrum treatment resistance. Custirsen (OGX-011) is a 2'-methoxyethyl modified phosphorothioate ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543780802528609

    authors: Chi KN,Zoubeidi A,Gleave ME

    更新日期:2008-12-01 00:00:00

  • Berberine: a potential phytochemical with multispectrum therapeutic activities.

    abstract:IMPORTANCE OF THE FIELD:The use of traditional medicines of natural origin is being encouraged for the treatment of chronic disorders, as synthetic drugs in such cases may cause unpredictable adverse effects. Berberine, a traditional plant alkaloid, is used in Ayurvedic and Chinese medicine for its antimicrobial and an...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.2010.517745

    authors: Vuddanda PR,Chakraborty S,Singh S

    更新日期:2010-10-01 00:00:00

  • Armodafinil: a new treatment for excessive sleepiness.

    abstract:BACKGROUND:Armodafinil is a wake-promoting agent developed by Cephalon that was approved in mid-2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder. It is the R-enantiomer of the compound modafinil. Like modafinil, the mechanism of action for armoda...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543784.17.4.565

    authors: Lankford DA

    更新日期:2008-04-01 00:00:00

  • Suppression of farnesyltransferase activity in acute myeloid leukemia and myelodysplastic syndrome: current understanding and recommended use of tipifarnib.

    abstract:IMPORTANCE OF THE FIELD:Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) incidence in the United States increases with age. Given the progressive ageing of the general population, incidence of these diseases is likely to continue to rise in the future. There is an acute need for therapeutic developments ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1517/13543781003801076

    authors: Epling-Burnette PK,Loughran TP Jr

    更新日期:2010-05-01 00:00:00

  • Prorenin receptor blockers: effects on cardiovascular complications of diabetes and hypertension.

    abstract::When the 'handle region' of the prorenin prosegment interacts with the (pro)renin receptor, the prorenin molecule partially changes the conformation to an enzymatically active state. On the other hand, the receptor triggers its own intracellular signalling pathways independent of the renin-angiotensin system (RAS). Th...

    journal_title:Expert opinion on investigational drugs

    pub_type: 社论,评审

    doi:10.1517/13543784.15.10.1137

    authors: Ichihara A,Kaneshiro Y,Suzuki F

    更新日期:2006-10-01 00:00:00

  • Experimental therapies targeting apolipoprotein C-III for the treatment of hyperlipidemia - spotlight on volanesorsen.

    abstract:INTRODUCTION:Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审

    doi:10.1080/13543784.2019.1582028

    authors: Milonas D,Tziomalos K

    更新日期:2019-04-01 00:00:00