Diabetes Division, UT Health, San Antonio, TX, USA.
University of Padova, Padova, Italy.
Lancet Diabetes Endocrinol. 2024 Sep;12(9):674-680. doi: 10.1016/S2213-8587(24)00127-X. Epub 2024 Aug 1.
Glucagon-like peptide-1 (GLP-1) receptor agonists have gained widespread use in the treatment of individuals with type 2 diabetes because of their potent weight loss promoting effect, ability to augment β-cell function, and cardiovascular protective effects. However, despite causing impressive weight loss, GLP-1 receptor agonists do not normalise insulin sensitivity in people with type 2 diabetes and obesity, and the long-term effects of this class of antidiabetic medication on muscle mass, frailty, and bone density have been poorly studied. Although GLP-1 receptor agonists improve insulin sensitivity secondary to weight loss, the only true direct insulin-sensitising drugs are thiazolidinediones. Because of side-effects associated with type 2 diabetes therapy, these drugs have not gained widespread use. In lieu of the important role of insulin resistance in the cause of type 2 diabetes and in the pathogenesis of atherosclerotic cardiovascular disease in type 2 diabetes, development of potent insulin-sensitising drugs that can be used in combination with GLP-1 receptor agonists remains a large unmet need in the management of individuals with type 2 diabetes.
胰高血糖素样肽-1（GLP-1）受体激动剂因其强大的减肥作用、增强β细胞功能和心血管保护作用，已广泛用于治疗 2 型糖尿病患者。然而，尽管 GLP-1 受体激动剂能显著减轻体重，但它们并不能使 2 型糖尿病和肥胖患者的胰岛素敏感性正常化，而且这类抗糖尿病药物对肌肉量、虚弱和骨密度的长期影响研究甚少。尽管 GLP-1 受体激动剂通过减轻体重来改善胰岛素敏感性，但唯一真正的直接胰岛素增敏药物是噻唑烷二酮类。由于与 2 型糖尿病治疗相关的副作用，这些药物并未广泛使用。鉴于胰岛素抵抗在 2 型糖尿病发病机制和 2 型糖尿病动脉粥样硬化性心血管疾病发病机制中的重要作用，开发可与 GLP-1 受体激动剂联合使用的强效胰岛素增敏药物，仍然是 2 型糖尿病患者管理中的一个巨大未满足需求。
