Composite retinopathy outcome in patients treated with empagliflozin versus placebo in the EMPA-REG OUTCOME trial

Aims:

In the EMPA-REG OUTCOME trial of patients with type 2 diabetes and cardiovascular (CV) disease, empagliflozin reduced the relative risk of 3-point major adverse CV events by 14%, driven by a 38% reduction in CV death. In addition, the relative risk of a pre-specified composite microvascular outcome (time to first retinal photocoagulation, vitreous haemorrhage, diabetes-related blindness, or incident or worsening nephropathy) was reduced by 38%, driven by the renal component. We analysed empagliflozin treatment on retinopathy in EMPA-REG OUTCOME.

Methods:

Patients were randomised to empagliflozin 10 mg or 25 mg, or placebo. Post hoc, we assessed the risk of a composite retinopathy outcome (time to first retinal photocoagulation, vitreous haemorrhage, diabetes-related blindness, or administration of intravitreal agents). Differences in risk between the pooled empagliflozin and placebo groups were assessed using a Cox proportional hazards model in patients treated with ≥1 dose of study drug. We also assessed the risk of this composite outcome after week 12 by reduction in HbA1c at week 12 (< 1% and ≥1%).

Results:

No difference between empagliflozin and placebo in risk of the composite retinopathy outcome (HR 0.78 [95%CI 0.54, 1.12]; p = 0.1732) nor its components was observed. The risk of this composite outcome (empagliflozin vs. placebo) after week 12 was similar, irrespective of HbA1c reduction at week 12 (< 1%: HR 0.87 [95%CI 0.58, 1.31]; ≥1%: HR 0.40 [95%CI 0.14, 1.14]) (p = 0.1755 for treatment by subgroup interaction).

Conclusion:

In EMPA-REG OUTCOME, there was no difference in risk of retinopathy between empagliflozin and placebo.