SGLT-2 Inhibitors Reduce Glaucoma Risk in Type 2 Diabetes Patients

SGLT-2 inhibitors may reduce the risk of glaucoma in patients with type 2 diabetes mellitus (T2DM) compared to GLP-1 agonists or DPP-4 inhibitors, according to new research.¹

A study presented at the 127th Annual American Academy of Ophthalmology (AAO) Congress in San Francisco, California, this week showed the popular drug class for type 2 diabetes management is additionally associated with reduced overall incident glaucoma compared to competitor drug classes. The findings warrant further analysis into the prospective ophthalmic risk-reduction benefit of agents including dapagliflozin and empagliflozin among patients with T2DM.

The concept of benefitting eye health with cardiometabolic-indicated therapy is not previously unfounded. A trial from the Association for Research in Vision and Ophthalmology (ARVO) 2021 Virtual Sessions suggested a potential benefit of dapagliflozin for the treatment of patients with diabetic retinopathy (DR). Particularly, early-stage research showed the SGLT-2 inhibitor had positive effect on glycemic control and potentially anti-inflammatory and anti-angiogenic effect on animal models.²

In this new study from AAO 2023, presented by Kathleen Eng, BA, of Harvard Medical School, looked to build on the limited research into the associated risk of glaucoma in patients with T2DM receiving SGLT-2 inhibitors.¹ Per their research, a multi-institutional cohort study in Taiwan involving approximately 11,000 patients showed a decreased risk of incident glaucoma among patients with T2DM. Another meta-analysis of randomized, controlled trials showed no correlation between SGLT-2 inhibitors and glaucoma risk in patients with T2DM.

“Given microvascular remodeling hypotheses for glaucoma, could SGLT-2 inhibitors decrease glaucoma risk in those with T2DM?” the team prosed.

Eng and colleagues conducted their own multicenter cohort analysis across US facilities from 2013 – 2023. They compared the risk of incident glaucoma in adult patients with T2DM on SGLT-2 inhibitors to a 1:1 propensity score-matched cohort of patients with T2DM receiving DDP-4 inhibitors.

The team additionally conducted a sensitivity analysis comparing incident risk relative to a cohort of patients receiving GLP-1 agonists for their T2DM. The primary outcome was incidence of new onset billing diagnosis codes for glaucoma in treated patients.

Compared with patients treated with DDP-4 inhibitors, patients who received SGLT-2 inhibitors for their T2DM reported a 21.5% reduced risk of overall glaucoma incidence (hazard ratio [HR], 0.795; 95% CI, 0.781 – 0.810; P <.001).

Similar risk reductions were observed for glaucoma subtypes including open-angle glaucoma (HR, 0.747; 95% CI, 0.722 – 0.773; P <.001) and primary angle-closure glaucoma (HR, 0.693; 95% CI, 0.625 – 0.768; P <.001). However, risk for pigmentary glaucoma was essentially similar across patients receiving SGLT-2 inhibitors or DPP-4 inhibitors for their T2DM (HR, 1.003; 95% CI, 0.778 – 1.293; P = .981).

Investigators also observed a protective effect of SGLT-2 inhibitor versus glaucoma when compared to patients receiving GLP-1 agonists, though not for all disease subtypes. They believe the mechanism of benefit with SGLT-2 inhibitors is likely multifactorial, and dependent on the subtype of glaucoma.

Though the trial was limited by uncertainty of glaucoma severity and disease progression, the findings warrant validation studies and an exploration into the potential mechanisms of action that which positively effect patients with T2DM receiving SGLT-2 inhibitors. They additionally provide a new consideration to prescribing strategies for type 2 diabetes.

“The use of SGLT2 inhibitors was associated with a significantly decreased risk of glaucoma in patients with T2D,” investigators concluded.

References

1. ^{Eng K, Huang P, Zebardast N, Friedman DS, et al. Sodium-Glucose Cotransporter 2 Inhibitors and Decreased Risk of Glaucoma in Patients with Type 2 Diabetes Mellitus. Abstract presented at: American Academy of Ophthalmology Congress. San Francisco, CA. November 3 – 6, 2023.}
2. ^{Kunzmann K. Could Dapagliflozin Treat Diabetic Retinopathy? HCPLive. Published May 5, 2021. https://www.hcplive.com/view/could-dapagliflozin-treat-diabetic-retinopathy}