Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Sep 22;17(9):e92976.
doi: 10.7759/cureus.92976. eCollection 2025 Sep.

Microvascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review of Retinopathy and Nephropathy Evidence

Atia Arif  1 , Sanu Lama  2   3 , Bhavna Singla  4 , Shivam Singla  5 , Sunita Kumawat  6 , Anusha Tharwani  7 , Muhammad Usman  8 , Hamna Khalid  8 , Venkata Madusudana Rao Kanukollu  9 , Osatohanmwen Ekomwereren  10 , Shabir Khan  11
Affiliations
Review

Microvascular Outcomes of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Type 2 Diabetes: A Systematic Review of Retinopathy and Nephropathy Evidence

Atia Arif et al. Cureus. .

Abstract

This systematic review evaluated randomized controlled trials examining the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on microvascular outcomes in type 2 diabetes, focusing on diabetic retinopathy and nephropathy. Four eligible RCTs, enrolling over 27,000 patients with follow-up periods ranging from 32 weeks to 5.4 years, were included. GLP-1 receptor agonists consistently demonstrated renal protective effects, primarily driven by reductions in new or worsening nephropathy and macroalbuminuria, with more modest and inconsistent effects on estimated glomerular filtration rate (eGFR) decline. In contrast, their impact on retinopathy remained inconclusive. A transient signal of worsening retinopathy has been reported in the context of rapid glycemic improvement; however, across large outcome trials, effects on retinopathy have been inconsistent and remain inconclusive. Overall, the evidence for retinopathy risk is limited by small event numbers, heterogeneity in assessments, and exploratory analyses. The certainty of renal benefit was strengthened by rigorous trial designs and low risk of bias, whereas retinopathy outcomes were generally secondary and less robust. These findings suggest that GLP-1 receptor agonists can be prioritized for patients at high renal risk, but careful monitoring of individuals with pre-existing retinopathy remains warranted.

Keywords: diabetic nephropathy; diabetic retinopathy; glp-1 receptor agonists; microvascular complications; randomized controlled trials; type 2 diabetes.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. The PRISMA flow diagram is illustrating the process of selection the studies.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses
See this image and copyright information in PMC

References

    1. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402:203–234. - PMC - PubMed
    1. Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation. Kropp M, Golubnitschaja O, Mazurakova A, et al. EPMA J. 2023;14:21–42. - PMC - PubMed
    1. Renal disease in patients with type 2 diabetes: magnitude of the problem, risk factors and preventive strategies. Gnudi L. Presse Med. 2023;52:104159. - PubMed
    1. Glycemic control for patients with type 2 diabetes mellitus: our evolving faith in the face of evidence. Rodríguez-Gutiérrez R, Montori VM. Circ Cardiovasc Qual Outcomes. 2016;9:504–512. - PMC - PubMed
    1. Glycaemic control and macrovascular and microvascular outcomes: a systematic review and meta-analysis of trials investigating intensive glucose-lowering strategies in people with type 2 diabetes. Kunutsor SK, Balasubramanian VG, Zaccardi F, Gillies CL, Aroda VR, Seidu S, Khunti K. Diabetes Obes Metab. 2024;26:2069–2081. - PubMed

LinkOut - more resources