Title:Association between Glucose-lowering Treatments and Risk of Diabetic
Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study
Volume: 19
Issue: 2
Author(s): Jakob Hasselstrøm Jensen, Peter Vestergaard and Morten Hasselstrøm Jensen*
Affiliation:
- Steno Diabetes
Center North Denmark, Aalborg University Hospital, Hobrovej 19, 9100, Aalborg, Denmark
- Department of Health
Science and Technology, Aalborg University, Fredrik Bajers Vej 7, 9220, Aalborg, Denmark
Keywords:
Diabetic retinopathy, type 2 diabetes, glucose-lowering treatment, antidiabetic treatment, risk factors, arterial hypertension.
Abstract:
Introduction: Glycaemic variability is possibly linked to the development of diabetic
retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce
glycaemic variability.
Aim: This study aimed to investigate whether newer second-line glucose-lowering treatments are
associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes.
Methods: A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering
treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted
time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model
was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income,
history of late-diabetic complications, history of non-fatal major adverse cardiovascular events,
history of chronic kidney disease, and history of hypoglycaemic episodes.
Results: Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin
+ glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were
associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl
peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium–glucose cotransporter-2 inhibitor
(SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of
diabetic retinopathy compared with all regimens investigated.
Conclusion: Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second-
line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However,
many other considerations concerning the choice of second-line glucose-lowering treatment
for type 2 diabetes patients should be taken into account.
