Risk of diabetic retinopathy and diabetic macular oedema with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database.

Eleftheriadou, Aikaterini, Riley, David, Zhao, Sizheng S ORCID: 0000-0002-3558-7353, Austin, Philip, Hernández, Gema, Lip, Gregory YH ORCID: 0000-0002-7566-1626, Jackson, Timothy L, Wilding, John PH ORCID: 0000-0003-2839-8404 and Alam, Uazman ORCID: 0000-0002-3190-1122 (2024) Risk of diabetic retinopathy and diabetic macular oedema with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database. Diabetologia. pp. 1-12.

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Official URL: http://dx.doi.org/10.1007/s00125-024-06132-5

Abstract

<h4>Aims/hypothesis</h4>A protective role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin.<h4>Methods</h4>This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan-Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA<sub>1c</sub>, BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed.<h4>Results</h4>SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208).<h4>Conclusions/interpretation</h4>Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated retinal imaging are required to determine the causal relationship with these therapies.

Item Type:	Article
Uncontrolled Keywords:	Clinical diabetes, Microvascular disease, Retinopathy
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	17 Apr 2024 09:03
Last Modified:	29 Apr 2024 03:05
DOI:	10.1007/s00125-024-06132-5
Open Access URL:	https://doi.org/10.1007/s00125-024-06132-5
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3180390