Abstract
Purpose :
Glucagon-like peptide-1 receptor (GLP1R) agonists are a class of incretin mimetics used to treat type 2 diabetes by augmenting insulin release and sensitivity. Despite improved glycemic control, clinical trials have shown a transient worsening of diabetic retinopathy in some patients treated with GLP1R agonists. We examined this paradoxical worsening and assessed risk for progression of nonproliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), and in particular, proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME).
Methods :
A retrospective cohort of patients with NPDR newly started on a GLP1R agonist from a national insurance claims database was compared to a cohort of patients treated with other oral agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusion occurred for <2 years in database before diagnosis; prior diagnosis of PDR, DME, vitreous hemorrhage, other retinal vascular diseases; or prior VTDR treatment. Primary outcomes were incidence of VTDR, PDR, and DME. Inverse probability of treatment weight (IPTW) was used within a multivariable Cox proportional hazard regression model to test the association between GLP1R agonist exposure and progression to VTDR, PDR and DME. IPTW was derived from a propensity score model based on Diabetic Complications Severity index, hemoglobin A1c (HbA1c), demographic factors and systemic health conditions. HbA1c was modeled in a time-updating fashion.
Results :
3,668 GLP1R users meeting inclusion criteria were matched to 4,821 unexposed controls. In the GLP1R cohort, 132 (3.6%), 22 (0.6%) and 118 (3.2%) patients progressed to VTDR, PDR and DME, respectively. This compared to 353 (7.3%) VTDR, 156 (3.2%) PDR, and 242 (5.0%) DME patients in the control group. Accounting for underlying DM severity with IPTW, GLP1R agonist use conferred a reduced hazard of developing VTDR (hazard ratio [HR] = 0.44, 95% CI: 0.38-0.50, p<0.001), PDR (HR = 0.16, 95% CI: 0.12-0.22, p<0.001), and DME (HR = 0.57, 95% CI: 0.49-0.66, p<0.001).
Conclusions :
GLP1R agonist use was associated with statistically significant and clinically meaningful reductions in progression from NPDR to VTDR, PDR, and DME. These results may have implications in treatment choice for patients with diabetic retinopathy.
This is a 2021 ARVO Annual Meeting abstract.