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
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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.

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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。
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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
Effect of weight-maintaining ketogenic diet on glycemic control and insulin sensitivity in obese T2D subjects. National health and economic impact of a lifestyle program to prevent type 2 diabetes mellitus in Germany: a simulation study. Ethnic-specific oral glucose tolerance (OGTT) phenotypes in women with hyperglycemia in pregnancy. Recent trends in GLP-1 RA and SGLT2i use among people with type 2 diabetes and atherosclerotic cardiovascular disease in the USA. Applying machine learning approaches for predicting obesity risk using US health administrative claims database.
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