Effect of Tight Glycemic Control on Microvascular Complications in Type 2 Diabetes Mellitus — a Randomized Controlled Trial in an Egyptian Cohort

Abstract

Objective: To compare the effects of a tight glycated hemoglobin (HbA1c) target (< 7.0%) versus a less tight target (< 7.5%) on microvascular complications in adults with poorly controlled type 2 diabetes (T2D) in Egypt. Material and methods: In this parallel-group, randomized controlled trial, 80 adults (18–60 years) with T2D, baseline HbA1c > 7.5%, and mild-to-moderate non-proliferative diabetic retinopathy (NPDR) were randomized by computer-generated simple randomization to a tight target (Group A; n = 33) or a less tight target (Group B; n = 47) and followed for 6 months. Glycemic indices, renal parameters (albumin-to-creatinine ratio and estimated glomerular filtration rate), and neuropathy (Douleur Neuropathique 4 questionnaire) were assessed at baseline and 6 months. Retinopathy worsening was defined as ≥ 1-step progression on the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Results: At 6 months, Group A achieved lower HbA1c than Group B [6.23% ± 0.35 (45 mmol/mol) vs. 7.27% ± 0.23 (56 mmol/mol); p < 0.001], with lower fasting plasma glucose and 2-hour postprandial glucose (both p < 0.001). Retinopathy worsening occurred more frequently in Group A than Group B (63.6% vs. 14.9%; p < 0.001). Overall new-onset or progressive microvascular complications were higher in Group A (84.8%) than Group B (31.9%; p < 0.001), including albuminuria (36.4% vs. 14.9%; p = 0.026) and neuropathy (39.4% vs. 10.6%; p = 0.002). Conclusions: Although tighter glycemic targets improved glycemic indices, they were associated with substantially higher short-term retinopathy worsening and greater overall microvascular deterioration. Individualized targets and gradual HbA1c reduction with close ophthalmologic follow-up may mitigate early worsening risk. Trial registration: ClinicalTrials.gov NCT07049601.