Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Graefes Arch Clin Exp Ophthalmol. 2024 Mar;262(3):717-752. doi: 10.1007/s00417-023-06236-5. Epub 2023 Sep 20.
Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic.
糖尿病视网膜病变（DR）是美国劳动人口失明的主要病因。其长期管理依赖于有效的血糖控制。在过去的二十年中，已经为 2 型糖尿病（T2D）患者引入了七种抗糖尿病药物类别，它们具有不同的降血糖和心血管益处。然而，它们对 DR 的具体影响尚未详细研究。对文献进行了系统回顾，以调查这一主题，重点是 T2D 的现有临床数据。根据统计学证据水平评估已发表的研究，只要它们至少包含一个与视网膜健康相关的终点或不良事件。符合纳入标准的有 59 篇文章，按抗糖尿病药物类别分组如下：α-葡萄糖苷酶抑制剂（1）、过氧化物酶体增殖物激活受体 γ（PPAR-γ）激动剂（8）、胰淀素类似物（1）、胰高血糖素样肽-1（GLP-1）受体激动剂（28）、二肽基肽酶 4（DPP-4）抑制剂（9）和钠葡萄糖协同转运蛋白-2（SGLT-2）抑制剂（9），外加一项回顾性研究和两项评估上述抗糖尿病类别中超过一种药物的荟萃分析。我们还审查了最近推出的 twincretin 类药物的试验的公开结果。现有数据表明，大多数新型抗糖尿病药物类别对 DR 进展无影响；然而，特定药物和 T2D 人群的亚类存在差异。特别是，有证据表明，PPAR-γ 激动剂可能会导致糖尿病性黄斑水肿恶化，semaglutide（GLP-1 受体激动剂）可能会轻微恶化 DR，SGLT-2 抑制剂可能会导致老年患者和晚期肾病患者视网膜静脉阻塞的发生率略有增加。所有这些都需要进一步研究。未来 T2D 领域的所有试验都强烈建议进行更长时间的随访和对至少一个与 DR 相关的终点进行系统评估，以最终解决这一问题。
