Renal Safety of Intravitreal Ranibizumab and the Effects of SGLT2 Inhibition in Diabetic Macular Oedema: A Post Hoc Analysis of the COMET Trial

Why clinicians should know about it

• Picked for Bariatric and Metabolic Surgery (top studies of the week, 13 September 2026): Renal safety of intravitreal ranibizumab, ophthalmology, not bariatric surgery
• Picked for Nephrology (top studies of the week, 13 September 2026): Ranibizumab exposure not linked to renal function decline

Abstract

AIMS: To evaluate whether intravitreal ranibizumab (IVR) frequency is associated with longitudinal renal markers in diabetic macular oedema (DMO) and whether the expected systemic renal and haematological effects of SGLT2 inhibition are reproduced. MATERIALS AND METHODS: In this post hoc sub-analysis of the prospective COMET randomised controlled trial, 53 participants were analysed. The estimated glomerular filtration rate (eGFR), haematocrit (Hct), and urinary albumin-to-creatinine ratio (UACR) were assessed over 48 weeks using linear mixed-effects models with the treatment group, week, group-by-week interaction, and cumulative IVR as fixed effects. RESULTS: Baseline eGFR was preserved (72.2 ± 18.5 mL/min/1.73 m2) despite common albuminuria (median UACR 50.6 mg/gCr); mean cumulative IVR at week 48 was 7.00 ± 4.42. Cumulative IVR was not significantly associated with eGFR (-0.22 mL/min/1.73 m2 per injection; 95% CI -0.59 to 0.15; p = 0.25), ln(UACR), or Hct. The SGLT2 inhibitor reproduced an early eGFR dip and Hct rise. CONCLUSIONS: No statistically significant exposure-response association was detected between cumulative IVR and renal markers within the COMET trial cohort and dosing range. Because all participants received IVR and the sample size was modest, small cumulative renal effects cannot be excluded. TRIAL REGISTRATION: University Hospital Medical Information Network Center (UMIN000057674); Japan Registry of Clinical Trials (jRCTs031180210, parent COMET trial).

Abstract as published, via PubMed.