» Articles » PMID: 38239984

Associations of Antidiabetic Drugs with Diabetic Retinopathy in People with Type 2 Diabetes: an Umbrella Review and Meta-analysis

Abstract

Background: Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.

Methods: A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).

Results: With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).

Conclusion: Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.

Citing Articles

Impact of duration of treatments with metformin and sulfonylureas, individually or in combination, on diabetic retinopathy among newly diagnosed type 2 diabetic patients: a pooled cohort's analysis.

Bahardoust M, Mehrabi Y, Hadaegh F, Khalili D, Delpisheh A Int J Retina Vitreous. 2025; 11(1):9.

PMID: 39891223 PMC: 11784098. DOI: 10.1186/s40942-025-00637-w.


Diabetes Renders Photoreceptors Susceptible to Retinal Ischemia-Reperfusion Injury.

Antonetti D, Lin C, Shanmugam S, Hager H, Cao M, Liu X Invest Ophthalmol Vis Sci. 2024; 65(13):46.

PMID: 39570639 PMC: 11585066. DOI: 10.1167/iovs.65.13.46.


Forecasting the Pharmacological Mechanisms of and in Diabetic Retinopathy Treatment: A Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Study.

Sahu N, Tyagi R, Kumar N, Mujeeb M, Akhtar A, Alam P Biology (Basel). 2024; 13(9).

PMID: 39336159 PMC: 11429473. DOI: 10.3390/biology13090732.


Repurposing metabolic regulators: antidiabetic drugs as anticancer agents.

Dhas Y, Biswas N, M R D, Jones L, Ashili S Mol Biomed. 2024; 5(1):40.

PMID: 39333445 PMC: 11436690. DOI: 10.1186/s43556-024-00204-z.

References
1.
Andreadis P, Karagiannis T, Malandris K, Avgerinos I, Liakos A, Manolopoulos A . Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes Obes Metab. 2018; 20(9):2255-2263. DOI: 10.1111/dom.13361. View

2.
Pollock M, Fernandes R, Newton A, Scott S, Hartling L . The impact of different inclusion decisions on the comprehensiveness and complexity of overviews of reviews of healthcare interventions. Syst Rev. 2019; 8(1):18. PMC: 6329144. DOI: 10.1186/s13643-018-0914-3. View

3.
Bethel M, Diaz R, Castellana N, Bhattacharya I, Gerstein H, Lakshmanan M . HbA Change and Diabetic Retinopathy During GLP-1 Receptor Agonist Cardiovascular Outcome Trials: A Meta-analysis and Meta-regression. Diabetes Care. 2021; 44(1):290-296. PMC: 7783944. DOI: 10.2337/dc20-1815. View

4.
Wang F, Mao Y, Wang H, Liu Y, Huang P . Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. Clin Drug Investig. 2021; 42(1):17-28. DOI: 10.1007/s40261-021-01110-w. View

5.
Drucker D . Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1. Cell Metab. 2018; 27(4):740-756. DOI: 10.1016/j.cmet.2018.03.001. View