GLP-1RAs is a class of anti-diabetic drugs that mimic the action of endogenous glucagon-like peptide-1 (GLP-1). GLP-1RAs significantly improves glycemic control in patients with type 2 diabetes by binding to and activating GLP-1 receptors to stimulate insulin secretion and inhibit glucagon release in a glucose-dependent manner [[1], [2], [3], [4], [5]]. In diabetes management, this class of drugs not only provides effective hypoglycemic effects, but also effectively promotes weight loss, which is mainly achieved by inducing satiety and reducing food intake through central action [[6], [7], [8]]. In addition, GLP-1RAs has been shown to have cardiovascular protective effects, which can significantly reduce the risk of cardiovascular events, such as myocardial infarction and stroke, especially in patients with established cardiovascular disease or high risk of diabetes. GLP-1RAs are recommended as the first choice of treatment in guidelines and have also shown a positive effect in renal protection [[9], [10], [11], [12], [13]]. This also includes protection of islet β-cell function, promotion of β-cell proliferation, and potential neuroprotective effects, such as potential benefits against cognitive impairment and neurodegenerative diseases, further extending its value in the management of diabetes and related complications [[14], [15], [16]].

DR is defined as a microvascular complication mainly caused by diabetes, involving retinal vascular damage and dysfunction, which seriously affects the quality of life and work ability of patients [[17], [18], [19]]. It is a chronic, progressive disease characterized by impaired microcirculation, including retinal ischemia, neovascularization, and blood-retinal barrier destruction. DR is considered to be the most common and typical microvascular complication of diabetes (Fig. 1) [[20], [21], [22]]. Due to the long-term hyperglycemic state, DR leads to abnormal retinal capillary structure and function [23]. It affects about 25–33 % of people with diabetes, and is vision-threatening in about 6 % of people with DR worldwide [[24], [25], [26]]. Without treatment, DR can progress to irreversible visual impairment, including permanent blindness, especially in severe stages [27,28]. DR is divided into two major subtypes: non-proliferative DR (NPDR) and proliferative DR (PDR), which reflect early microvascular abnormalities (such as leakage and bleeding) and late severe lesions (such as neovascularization) [29]. In addition, DR is also associated with an increased risk of diabetic macrovascular complications such as cardiovascular disease, suggesting that it can be used as a sensitive indicator of systemic vascular damage [30,31]. The global burden of DR is expected to grow as the incidence of diabetes rises, making it a public health challenge [[26], [27], [28]]. DR is not limited to microvascular damage, but also involves early neurodegeneration (such as neuronal and glial cell damage), which is considered as a neurovascular complication rather than a pure vascular disease [[32], [33], [34], [35]].

The relationship between GLP-1RAs and DR is significantly controversial, mainly reflected in the inconsistent results of potential increased risk and protective effects. On the one hand, several studies have reported that GLP-1RAs may increase the risk of the onset and progression of DR. For example, from the FDA Adverse Event Reporting System (FAERS), some GLP-1RAs have been shown to be significantly associated with DR events, including diabetic macular edema and proliferative diabetic retinopathy [36,37]. On the other hand, GLP-1RAs has a potential protective effect, and retrospective cohort analysis shows that it is superior to other hypoglycemic drugs in controlling the progression of DR, partly due to its role in restoring the down-regulation of GLP-1 receptor expression in retinal vascular endothelial cells, thereby improving retinal degeneration and tortuosity of retinal vessels [38]. The controversy stems from comparisons between different drugs. Some studies have found that, compared with sodium-dependent glucose transporter 2 (SGLT-2) inhibitors, DR exacerbation rate of GLP-1RAs is inconsistent in different series [39,40]. Therefore, this article discusses the role of GLP-1RAs in DR from multiple perspectives to provide a more comprehensive evaluation and analysis (Table I).