Purpose This study aimed to compare anatomical and functional outcomes between patients with non-proliferative diabetic retinopathy (NPDR) with diabetic macular oedema (DME) who adhered to intravitreal aflibercept therapy and patients lost to follow-up (LTFU). Methods We enrolled 200 patients and recorded the interval between each procedure and the subsequent follow-up visit. Moreover, visual acuity (VA) and anatomical outcomes were measured at each follow-up examination. Results Among the patients, 103 (51%) patients adhered to intravitreal aflibercept therapy and follow-up examination while 97 (49%) patients were LTFU. Forty-six (47%) patients LTFU who returned for further treatment showed a significant decrease in VA from 0.51 (±0.46) to 0.89 (±0.38) logarithm of the minimum angle of resolution (logMAR) after 48 months (p = 0.004). Compared with the adherent group, the return group showed a worse VA at 48 months (p = 0.036). Further, 1 (1%) patient in the adherent group and 8 (17%) patients in the return group developed a proliferative DR. Patients who were LTFU had a 13.0 times greater chance to develop a proliferative DR (p = 0.022). Conclusions Patients who did not adhere to intravitreal aflibercept therapy for DME showed significantly worse visual outcomes compared to patients with good therapy adherence. Moreover, patients with LTFU had a 13 times higher risk of developing a proliferative DR. Considering the potential disease progress, better strategies should be applied to optimize the functional outcome of patients at risk of reduced adherence.