Abstract / Summary
Background: Diabetic peripheral neuropathy (DPN) is a serious complication of type 2 diabetes (T2DM). Guidelines recommend targeting modifiable risk factors for primary prevention, but their effectiveness is unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of interventions targeting modifiable risk factors to prevent DPN in adults with T2D.
Methods: We searched PubMed, Embase, and ClinicalTrials.gov databases for RCTs published since 1980 investigating glycemia, lipids, blood pressure (BP), smoking cessation, lifestyle, and multifactorial interventions. Two reviewers independently screened articles; a third reviewer resolved disagreements. Meta-analysis used a random-effects model. Results are reported as odds ratios (ORs) with 95% confidence and prediction intervals.
Results: From 1287 identified articles, 863 underwent title/abstract screening, with 41 full-text review, yielding nine studies with extractable data. Eight had low risk of bias (Cochrane RoB 1); one had unclear risk. The glycemic control meta-analysis (n = 5) yielded OR = 0.89 (95% CI 0.66-1.19; prediction interval 0.37-2.15; I2 = 77.8%). Sensitivity analysis identified BARI-2D as the dominant heterogeneity source; its removal reduced I2 to 23% and narrowed the prediction interval (0.80-1.08). This is clinically explainable: BARI-2D compared insulin-sensitizing versus insulin-providing drug strategies rather than glycemic intensity targets, in patients with coronary artery disease. The four-study analysis showed glycemic control may result in little to no difference in DPN risk (OR 0.93, 95% CI 0.85-1.02). In BARI-2D, an insulin-sensitizing strategy may reduce incident DPN independently of achieved HbA1c (0.84 (95% CI 0.71-0.99)) (low certainty). Single-study evidence suggests that BP-lowering and multifactorial interventions may reduce incident DPN (low certainty).
Discussion: Glycemic intensity interventions may result in little to no difference in incident DPN risk. The BARI-2D drug class-specific finding and single-study evidence suggesting benefit from BP-lowering and multifactorial interventions warrant further rigorous research on incident DPN.