Glucokinase activators and imeglimin: new weaponry in the armamentarium against type 2 diabetes.

IF 3.7 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM BMJ Open Diabetes Research & Care Pub Date : 2024-08-30 DOI:10.1136/bmjdrc-2024-004291
Åke Sjöholm
{"title":"Glucokinase activators and imeglimin: new weaponry in the armamentarium against type 2 diabetes.","authors":"Åke Sjöholm","doi":"10.1136/bmjdrc-2024-004291","DOIUrl":null,"url":null,"abstract":"<p><p>The prevalence of type 2 diabetes (T2D) is increasing relentlessly all over the world, in parallel with a similar increase in obesity, and is striking ever younger patients. Only a minority of patients with T2D attain glycemic targets, indicating a clear need for novel antidiabetic drugs that not only control glycemia but also halt or slow the progressive loss of β-cells. Two entirely novel classes of antidiabetic agents-glucokinase activators and imeglimin-have recently been approved and will be the subject of this review.Allosteric activators of glucokinase, an enzyme stimulating insulin secretion in β-cells and suppressing hepatic glucose production, are oral low-molecular-weight drugs. One of these, dorzagliatin, is approved in China for use in adult patients with T2D, either as monotherapy or as an add-on to metformin. It remains to be seen whether the drug will produce sustained antidiabetic effects over many years and whether the side effects that led to the discontinuation of early drug candidates will limit the usefulness of dorzagliatin.Imeglimin-which shares structural similarities with metformin-targets mitochondrial dysfunction and was approved in Japan against T2D. In preclinical studies, the drug has also shown promising β-cell protective and preservative effects that may translate into disease-modifying effects.Hopefully, these two newcomers will contribute to filling the great medical need for new treatment modalities, preferably with disease-modifying potential. It remains to be seen where they will fit in contemporary treatment algorithms, which combinations of drugs are effective and which should be avoided. Time will tell to what extent these new antidiabetic agents will add value to the current treatment options against T2D in terms of sustained antidiabetic effect, acceptable safety, utility in combination therapy, and impact on hard end-points such as cardiovascular disease.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367400/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMJ Open Diabetes Research & Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/bmjdrc-2024-004291","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

The prevalence of type 2 diabetes (T2D) is increasing relentlessly all over the world, in parallel with a similar increase in obesity, and is striking ever younger patients. Only a minority of patients with T2D attain glycemic targets, indicating a clear need for novel antidiabetic drugs that not only control glycemia but also halt or slow the progressive loss of β-cells. Two entirely novel classes of antidiabetic agents-glucokinase activators and imeglimin-have recently been approved and will be the subject of this review.Allosteric activators of glucokinase, an enzyme stimulating insulin secretion in β-cells and suppressing hepatic glucose production, are oral low-molecular-weight drugs. One of these, dorzagliatin, is approved in China for use in adult patients with T2D, either as monotherapy or as an add-on to metformin. It remains to be seen whether the drug will produce sustained antidiabetic effects over many years and whether the side effects that led to the discontinuation of early drug candidates will limit the usefulness of dorzagliatin.Imeglimin-which shares structural similarities with metformin-targets mitochondrial dysfunction and was approved in Japan against T2D. In preclinical studies, the drug has also shown promising β-cell protective and preservative effects that may translate into disease-modifying effects.Hopefully, these two newcomers will contribute to filling the great medical need for new treatment modalities, preferably with disease-modifying potential. It remains to be seen where they will fit in contemporary treatment algorithms, which combinations of drugs are effective and which should be avoided. Time will tell to what extent these new antidiabetic agents will add value to the current treatment options against T2D in terms of sustained antidiabetic effect, acceptable safety, utility in combination therapy, and impact on hard end-points such as cardiovascular disease.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
葡萄糖激酶激活剂和伊迈格列明:对抗 2 型糖尿病的新武器。
2 型糖尿病(T2D)的发病率在全世界持续上升,与此同时,肥胖症的发病率也同样上升,而且患者越来越年轻。只有少数 2 型糖尿病患者能达到血糖目标,这表明我们显然需要新型的抗糖尿病药物,它们不仅能控制血糖,还能阻止或减缓 β 细胞的逐渐丧失。葡萄糖激酶是一种刺激β细胞分泌胰岛素并抑制肝糖生成的酶,葡萄糖激酶的异位激活剂是一种口服低分子量药物。其中一种药物--多沙格列汀(dorzagliatin)已在中国获批用于治疗成年 T2D 患者,可作为单药或二甲双胍的辅助用药。Imeglimin在结构上与二甲双胍相似,针对线粒体功能障碍,已在日本获批用于治疗T2D。在临床前研究中,这种药物还显示出良好的β细胞保护和保存作用,这些作用可能会转化为改变疾病的效果。希望这两种新药将有助于满足医学界对新治疗方式的巨大需求,最好是具有改变疾病的潜力。至于这两种药物在现代治疗方案中的地位,以及哪些药物组合有效,哪些药物应避免使用,我们拭目以待。时间会证明这些新型抗糖尿病药物在多大程度上会增加目前治疗 T2D 的选择,包括持续的抗糖尿病效果、可接受的安全性、联合治疗的效用以及对心血管疾病等硬终点的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
BMJ Open Diabetes Research & Care
BMJ Open Diabetes Research & Care Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
9.30
自引率
2.40%
发文量
123
审稿时长
18 weeks
期刊介绍: BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of high-quality — and evidence-based — original research articles.
期刊最新文献
Association between RDW-SD and prognosis across glycemic status in patients with dilated cardiomyopathy. Widening the phenotypic spectrum caused by pathogenic PDX1 variants in individuals with neonatal diabetes. Identification of atypical pediatric diabetes mellitus cases using electronic medical records. Type 2 diabetes complications in ethnic minority compared with European host populations: a systematic review and meta-analysis. Effect of weight-maintaining ketogenic diet on glycemic control and insulin sensitivity in obese T2D subjects.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1