Response to Comment on Lee et al. Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Retinal Vein Occlusion Among Patients With Type 2 Diabetes: A Propensity Score–Matched Cohort Study. Diabetes Care 2021; 44:2419–2426

We would like to thank Feldman-Billard and Paques (1) for their interest in our article (2) and for expressing their concern that our findings could raise an overabundance of caution about the risk of retinal vein occlusion (RVO) associated with the new use of sodium–glucose cotransporter 2 (SGLT2) inhibitors in elderly patients with chronic kidney disease (CKD).

Feldman-Billard and Paques suggest a better quantification of the relationship between RVO risk and CKD. In subgroup analyses, we found 39 RVO events in patients with CKD, of which 28 cases occurred in the SGLT2 inhibitor group (incidence rate of 3.77 per 1,000 person-years) and 11 cases occurred in the other glucose-lowering drug group (incidence rate of 1.25 per 1,000 person-years). We additionally analyzed the RVO risk in SGLT2 inhibitor–treated patients with CKD compared with those without CKD. In the SGLT2 inhibitor group, the risk of RVO was higher in patients with CKD than in those without CKD (hazard ratio 1.821, 95% CI 1.403–2.365). We acknowledge these findings and recommend that the risk of RVO should be monitored in patients with impaired renal function.

Severe dehydration causes a reduction in effective plasma volume, resulting in RVO (3). The risk of dehydration is particularly high in patients with CKD (4). We agree with the comment of Feldman-Billard and Paques that the occurrence of RVO in patients with CKD is a transient phenomenon related to volume depletion after the initiation of SGLT2 inhibitor treatment. Unfortunately, owing to a lack of available data, we cannot confirm whether the time between SGLT2 inhibitor initiation and RVO occurrence differs between patients with and those without CKD. Care should be taken to avoid RVO due to dehydration when initiating SGLT2 inhibitor treatment in elderly patients with CKD.

As RVO incidence is low and a large sample size is needed, it is difficult to execute studies with a prospective approach. Therefore, this nationwide cohort study based on generalized population data bears clinical importance. However, SGLT2 inhibitors are known to have beneficial effects on metabolic, cardiovascular, and renal parameters (5). Further observational studies on the exact phenomenon and underlying mechanisms are needed to support our findings.

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