Glucocorticoid hormones were discovered to have use as potent anti-inflammatory and immunosuppressive therapeutics in the 1940s and their continued use and development have successfully revolutionized the management of acute and chronic inflammatory diseases. However, long-term use of glucocorticoids is severely hampered by undesirable metabolic complications, including the development of type 2 diabetes mellitus. These effects occur due to glucocorticoid receptor activation within multiple tissues, which results in inter-organ crosstalk that increases hepatic glucose production and inhibits peripheral glucose uptake. Despite the high prevalence of glucocorticoid-induced hyperglycaemia associated with their routine clinical use, treatment protocols for optimal management of the metabolic adverse effects are lacking or underutilized. The type, dose and potency of the glucocorticoid administered dictates the choice of hypoglycaemic intervention (non-insulin or insulin therapy) that should be provided to patients. The longstanding quest to identify dissociated glucocorticoid receptor agonists to separate the hyperglycaemic complications of glucocorticoids from their therapeutically beneficial anti-inflammatory effects is ongoing, with selective glucocorticoid receptor modulators in clinical testing. Promising areas of preclinical research include new mechanisms to disrupt glucocorticoid signalling in a tissue-selective manner and the identification of novel targets that can selectively dissociate the effects of glucocorticoids. These research arms share the ultimate goal of achieving the anti-inflammatory actions of glucocorticoids without the metabolic consequences.

糖皮质激素在 20 世纪 40 年代被发现可用作有效的抗炎和免疫抑制疗法，其持续使用和开发成功地彻底改变了急性和慢性炎症性疾病的治疗。然而，长期使用糖皮质激素会受到不良代谢并发症（包括 2 型糖尿病的发展）的严重阻碍。这些效应的发生是由于多个组织内的糖皮质激素受体激活，从而导致器官间串扰，从而增加肝葡萄糖的产生并抑制外周葡萄糖的摄取。尽管糖皮质激素引起的高血糖的患病率很高，但其代谢不良反应的最佳管理方案仍然缺乏或未得到充分利用。所用糖皮质激素的类型、剂量和效力决定了应向患者提供的降血糖干预（非胰岛素或胰岛素治疗）的选择。长期以来，人们一直在寻找解离的糖皮质激素受体激动剂，以将糖皮质激素的高血糖并发症与其治疗上有益的抗炎作用分开，选择性糖皮质激素受体调节剂正在临床测试中。临床前研究的前景广阔的领域包括以组织选择性方式破坏糖皮质激素信号传导的新机制，以及识别可以选择性解离糖皮质激素作用的新靶点。这些研究部门的共同最终目标是实现糖皮质激素的抗炎作用而不产生代谢后果。