Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
Handb Exp Pharmacol. 2023;280:107-129. doi: 10.1007/164_2022_590.
Tailoring treatment or management to groups of individuals based on specific clinical, molecular, and genomic features is the concept of precision medicine. Diabetes is highly heterogenous with respect to clinical manifestations, disease progression, development of complications, and drug response. The current practice for drug treatment is largely based on evidence from clinical trials that report average effects. However, around half of patients with type 2 diabetes do not achieve glycaemic targets despite having a high level of adherence and there are substantial differences in the incidence of adverse outcomes. Therefore, there is a need to identify predictive markers that can inform differential drug responses at the point of prescribing. Recent advances in molecular genetics and increased availability of real-world and randomised trial data have started to increase our understanding of disease heterogeneity and its impact on potential treatments for specific groups. Leveraging information from simple clinical features (age, sex, BMI, ethnicity, and co-prescribed medications) and genomic markers has a potential to identify sub-groups who are likely to benefit from a given drug with minimal adverse effects. In this chapter, we will discuss the state of current evidence in the discovery of clinical and genetic markers that have the potential to optimise drug treatment in type 2 diabetes.
根据特定的临床、分子和基因组特征，对个体进行分组治疗或管理是精准医学的概念。糖尿病在临床表现、疾病进展、并发症的发生和药物反应方面存在很大的异质性。目前的药物治疗实践主要基于临床试验的证据，这些证据报告的是平均效果。然而，尽管有很高的依从性，仍有一半左右的 2 型糖尿病患者未能达到血糖目标，而且不良结局的发生率存在很大差异。因此，有必要确定预测标志物，以便在开具处方时告知药物反应的差异。分子遗传学的最新进展和真实世界及随机试验数据的可用性增加，开始增加我们对疾病异质性及其对特定人群潜在治疗方法的影响的理解。利用简单的临床特征（年龄、性别、BMI、种族和同时开具的药物）和基因组标记物的信息，有可能确定可能从特定药物中受益且不良反应最小的亚组。在本章中，我们将讨论目前在发现有潜力优化 2 型糖尿病药物治疗的临床和遗传标志物方面的证据状况。
