Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium; Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liège, Liège, Belgium.
Presse Med. 2023 Mar;52(1):104158. doi: 10.1016/j.lpm.2022.104158. Epub 2022 Dec 22.
The pharmacotherapy of type 2 diabetes mellitus (T2DM) has markedly evolved in the last two decades. Classical antidiabetic agents (sulphonylureas, metformin, insulin) are now in competition with new glucose-lowering medications. Alpha-glucosidase inhibitors and thiazolidinediones (glitazones) were not able to replace older agents, because of insufficient efficacy and/or poor tolerability/safety. In contrast, incretin-based therapies, both dipeptidyl peptidase-4 inhibitors (DPP-4is or gliptins, oral agents) and glucagon-like peptide-1 receptor agonists (GLP-1RAs, subcutaneous injections) are a major breakthrough in the management of T2DM. Because they are not associated with hypoglycaemia and weight gain, DPP-4is tend to replace sulphonylureas as add-on to metformin while GLP-1RAs tend to replace basal insulin therapy after failure of oral therapies. Furthermore, placebo-controlled cardiovascular outcome trials demonstrated neutrality for DPP-4is, but cardiovascular protection for GLP-1RAs in patients with T2DM at high cardiovascular risk. More recently sodium-glucose cotransporter 2 inhibitors (SGLT2is or gliflozins, oral agents) also showed cardiovascular protection, especially a reduction in hospitalization for heart failure, as well as a renal protection in patients with and without T2DM, at high cardiovascular risk, with established heart failure and/or with chronic kidney disease. Thus, GLP-1RAs and SGLT2is are now considered as preferred drugs in T2DM patients with or at high risk of atherosclerotic cardiovascular disease whereas SGLT2is are more specifically recommended in patients with or at risk of heart failure and renal (albuminuric) disease. The management of T2DM is moving from a glucocentric approach to a broader strategy focusing on all risk factors, including overweight/obesity, and to an organ-disease targeted personalized approach.
在过去的二十年中，2 型糖尿病（T2DM）的药物治疗发生了显著的变化。经典的抗糖尿病药物（磺酰脲类、二甲双胍、胰岛素）现在与新的降糖药物竞争。由于疗效不足和/或耐受性/安全性差，α-葡萄糖苷酶抑制剂和噻唑烷二酮类（格列酮类）未能取代旧的药物。相比之下，基于肠促胰岛素的治疗方法，包括二肽基肽酶-4 抑制剂（DPP-4i 或gliptins，口服药物）和胰高血糖素样肽-1 受体激动剂（GLP-1RA，皮下注射），是 T2DM 治疗的重大突破。由于它们不与低血糖和体重增加相关，DPP-4i 倾向于取代磺酰脲类作为二甲双胍的附加药物，而 GLP-1RA 倾向于在口服治疗失败后取代基础胰岛素治疗。此外，安慰剂对照心血管结局试验表明 DPP-4i 中性，但 GLP-1RA 对高心血管风险的 T2DM 患者具有心血管保护作用。最近，钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i 或 gliflozins，口服药物）也显示出心血管保护作用，特别是在高心血管风险、已确诊心力衰竭和/或慢性肾脏病的患者中，降低心力衰竭住院率，以及在有或没有 T2DM 的患者中具有肾脏（白蛋白尿）保护作用。因此，GLP-1RA 和 SGLT2i 现在被认为是有或高动脉粥样硬化性心血管疾病风险的 T2DM 患者的首选药物，而 SGLT2i 更特别推荐用于有或有心力衰竭和肾脏（白蛋白尿）疾病风险的患者。T2DM 的治疗正在从以血糖为中心的方法转变为更广泛的策略，重点关注所有风险因素，包括超重/肥胖，以及针对器官疾病的个体化方法。
