Findings from a study recently published in the American Journal of Ophthalmology evaluated the effects of glucagon-like peptide-1 (GLP-1) agonists compared to sodium-glucose cotransporter-2 (SGLT-2) inhibitors on diabetic retinopathy (DR).
Give me some background.
DR is an ocular complication of diabetes mellitus (DM), secondary to damaged retinal blood vessels and ischemia that can potentially progress to vision-threatening severity.
Pharmacotherapy is prescribed to achieve glycemic control in diabetic patients and minimize the development of long-term micro- and macrovascular complications (i.e., DR).
Recently, several new classes of hypoglycemic agents have been approved by the FDA to improve blood sugar control—including GLP-1 agonists and SGLT-2 inhibitors.
How does this tie back to DR?
These novel therapies have become popular in recent years and are emerging as the new treatment standards for DM due to their beneficial effects on systemic and mortality outcomes.
However, the individual impact of these novel hypoglycemic agents on DR progression and vision-threatening complications (VTC) is not yet well established.
Now talk about the study.
In this retrospective clinical cohort study, investigators utilized TriNetX, a federated electronic health records (EHR) network comprised of global healthcare organizations.
With this data, researchers compared the rate and relative risk of progression to PDR and the rate of development of diabetic macular edema (DME) in patients on GLP-1 agonists versus those on SGLT-2 inhibitors.
Talk about the cohorts.
The research team included patients with an International Classification of Diseases, Tenth Revision (ICD-10) code of non-proliferative DR (NPDR) and monotherapy treatment (excluding insulin) with GLP-1 agonists or SGLT-2 inhibitors.
Patients with a history of proliferative diabetic retinopathy (PDR) prior to the initiation of treatment were excluded.
The groups were propensity score matched for:
- Age
- Gender
- Ethnicity
- Race
- Type of diabetes
- Severity of NPDR
Findings?
A total of 6,481 patients were identified in the GLP-1 cohort and the SGLT-2 inhibitor cohort after propensity score matching.
At 1 year and 3 years after therapy initiation, a higher rate of progression to PDR was noted in the GLP-1 agonist cohort compared to the SGLT-2 inhibitor group (relative risk [RR] 1.26, confidence interval [CI] 1.04-1.51, p=0.017 and RR: 1.284, CI 1.1-1.499, p=0.002, respectively).
Note: The relative risk is the ratio of the risk of an event in one group (i.e., GLP-1 group) versus the risk of the event in the other group (i.e., SGLT-2 group).
What about the risk of DME?
There was a higher rate of DME across multiple time points in the GLP-1 agonist arm compared to the SGLT-2 inhibitor arm:
- 3 months (RR 1.192, CI 1.059-1.276m p=0.002)
- 6 months (RR 1.22, CI 1.13-1.32, p<0.001)
- 1 year (RR 1.24, CI 1.15-1.33, p<0.001)
- 3 years (RR 1.29, CI 1.21-1.38, p<0.001)
The class-specific difference in developing VTCs became more pronounced over time.
Anything else?
At 3 years, besides a slightly higher need for anti-vascular endothelial growth factor (VEGF) therapies in the GLP-1 agonist group, there was no significant difference in mean hemoglobin A1c (HbA1c) levels or the need for secondary interventions between both groups.
Take home.
These findings suggest there is a higher rate of progression of PDR and risk of new-onset DME in patients on monotherapy with GLP-1 agonists compared to those on SGLT-2 inhibitors.
The study authors noted that understanding the potential ocular effects of these treatments and considering the current retinopathy status when initiating treatment with newer hypoglycemic agents is beneficial to ensuring these patients are appropriately monitored for the potential development of VTCs.