Change on glycosylated hemoglob with glucagon-like peptide-1 receptor agonists affecting the progress of diabetes retinopathy in type 2 diabetes– A systematic review and meta-analysis
Authors: Wang wenxuan , Lu jingyi , Li jing , Ma yuchen , Wang xin , Zhang fang , Li chunhui , Jiang jiajia , Hao yongmei 
Published: January 2024

Abstract
Background：Whether glucagon-like peptide-1 receptor agonists(GLP-1RA) has adverse effects on diabetes retinopathy(DR) due to blood glucose control is unclear.The main purpose of this article is to evaluate the effect of GLP-1RA or GLP-1RA combined with insulin on DR by inducing different degrees of glycosylated hemoglob(HbAlc).
Methods：This is a meta-analysis of 20 randomized controlled trial which including a total of 56204 type 2 diabetes(T2DM) patients.We used risk ration(RR) and 95% cofidence intervals(CIs) to estimate the influence of varying descending HbAlc levels in DR.
Results：GLP-1RA does not increase the risk of DR in T2DM,IDegLira was associated with an increased risk of DR (RR 1.69 95% CI 1.11-2.57), while the use of liraglutide did not increase the risk of DR (RR 0.70, 0.48-1.01). In the group with baseline glycation levels＜8.5% in the first 12 weeks, a decrease of over 1.5% in glycated hemoglobin was associated with an increased risk of DR (RR 1.75 95% CI 1.01-3.04), a decrease of 1% -1.5% in glycated hemoglobin reduced the risk of DR (RR 0.59 95% CI 0.37-0.93), and a decrease of＜1% in glycated hemoglobin was not associated with DR (RR 1.25 95% CI 0.93-1.69). In the group with baseline glycation levels ≥ 8.5% in the first 12 weeks, the decrease in glycated hemoglobin by more than 1.5% (RR 0.95 95% CI 0.66-1.38) and less than 1% (RR 0.77 95% CI 0.39-1.51) had no effect on DR. In the group with baseline glycation levels＜8.5% in the first 8 weeks, a decrease of 1% -1.5% in glycated hemoglobin (RR 0.94 95% CI 0.42-2.06), a decrease of less than 1% in glycated hemoglobin (RR 1.26 95% CI 0.62-2.59), and a decrease of more than 1.5% (RR 1.40 95% CI 0.68-2.87) had no effect on DR. In the group with baseline glycation levels ≥ 8.5% in the first 8 weeks, a decrease of less than 1% (RR 0.77 95% CI 0.39-1.51), and a decrease of 1% -1.5% (RR 1.09 95% CI 0.71-1.66) had no effect on DR. In the group with baseline glycation levels＜8.5% in the first 4 weeks, a decrease less than 0.5% (RR1.47 95% CI 0.47-4.58), 0.5% -＜1% (RR0.85 95% CI 0.30-2.46), and 1% -＜1.5% (RR1.40 95% CI 0.68-2.87) in glycated hemoglobin did not affect DR. In the group with baseline glycation levels ≥ 8.5%, a decrease of 0.5% -＜1% (RR0.99 95% CI 0.69-1.41) in glycated hemoglobin did not affect DR.The use of GLP-1RA combined with insulin did not increase the risk of DR (RR 1.24, 95% CI 0.90-1.71),however in the group with baseline glycation levels＜8.5% in the first 12 weeks,a decrease of over 1.5% in glycated hemoglobin was associated with an increased risk of DR (RR 1.75 95% CI 1.01-3.04).
Conclusions：When GLP-1RA is applied in T2DM patients with HbAlc level under 8.5%, controlling the decrease of HbAlc by 1% -1.5% in the first 12 weeks can reduce the risk of DR, and the decrease of HbAlc by more than 1.5% will increase the risk of DR.GLP-1RA combined with insulin does not show the risk of DR. The promoting effect by IDegLira in DR may be mediated by the quick variation of blood glucose.