Novel Antidiabetic Drugs and the Risk of Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background: The aim of this study is to compare the effect of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes (DM2). Methods: We systematically searched the databases Pubmed, Embase, and Clinicaltrials up to October 2, 2023, for randomized clinical trials (RCTs) of drugs from the GLP-1RA, SGLT-2i, and DPP-4i groups, with at least 24 weeks duration, including adult patients with DM2 and reported ocular complications. A pairwise meta-analysis was performed to calculate the odds ratio (OR) of DR incidents. Results: Our study included 61 RCTs with a total of 188,463 patients and 2773 DR events. Pairwise meta-analysis showed that included drug groups did not differ in the risk of DR events: GLP1-RA vs. placebo (OR 1.08; CI 95% 0.94, 1.23), DPP-4i vs. placebo (OR 1.10; CI 95% 0.84, 1.42), SGLT2i vs. placebo (OR 1.02; CI 95% 0.76, 1.37). Empagliflozin may be associated with a lower risk of DR, but this sub-analysis included only three RCTs (OR 0.38; 95% CI 0.17, 0.88, p = 0.02). Conclusions: Based on currently available knowledge, it is challenging to conclude that the new antidiabetic drugs significantly differ in their effect on DR complications.

Keywords: DPP-4i; GLP-1RA; SGLT-2i; antidiabetic drugs; diabetic retinopathy.

Figure 1

Pairwise meta-analysis, GLP-1RA vs. placebo [6,20,22,23,24,25,26,27,30,46,47,49,51,52,55,57,58,61,62,63,65,66,67,69,71,73,74].

Figure 2

Pairwise meta-analysis, DPP-4i vs. placebo [37,39,40,41,43,44,45,47,50,53,54,56,59].

Figure 3

Pairwise meta-analysis, SGLT-2i vs. placebo [33,34,35,36,38,42,48,68,70].