A Systematic Review and Meta-analysis of RCTs to Prevent Diabetic Neuropathy in Adults with Type 2 Diabetes

Introduction and Objective: Diabetic peripheral neuropathy (DPN) is a serious complication. Clinical guidelines recommend targeting modifiable risk factors to prevent DPN, but their effectiveness is unclear. We conducted a systematic review and meta-analysis to evaluate the effectiveness of treating modifiable risk factors to prevent DPN in adults with type 2 diabetes (T2D). Methods: Following PRISMA guidelines, Pubmed, Embase, and clinicaltrials.gov databases were searched for RCTs published since 1980 targeting glycemia, lipids, BP, obesity, smoking, lifestyle modification and multifactorial interventions. Two independent reviewers screened identified articles via Covidence. A third reviewer resolved disagreements. Meta-analysis for each intervention type was conducted using a random-effects model with R. Results are reported as ORs with 95% CI, p-values and I2 statistics. Results: We identified 832 articles from our search. After removal of duplicates and studies marked as ineligible through automated tools, 677 studies underwent title-abstract screening. Of these, 640 were deemed negative and 37 positives moved on to full-text screening. Another 9 studies were identified by non-systematic search. These 46 RCTs underwent full-text screening which yielded 12 studies with relevant extractable data. Meta-analysis was conducted for glycemic control: [n=6] (OR = 0.92, 95% CI 0.84: 1.01, p = 0.07, I2=0%); lifestyle: [n=2] (OR = 0.99, 95% CI 0.86: 1.13, p = 0.83, I2 = 0%) and multifactorial: [n=2] (OR =0.76, 95% CI 0.62: 0.93, p = 0.01, I2 = 0%). Insufficient high-quality RCTs were identified for lipid-lowering [n = 1], smoking cessation [n = 0], obesity [n = 0] and BP [n = 1] for meta-analysis. Conclusion: We found a reduced risk of DPN from multifactorial RCTs, borderline for glycemic control and no effect from lifestyle modification. These findings highlight the need for further research with incident DPN as outcome in adults with T2D to generate actionable results. Disclosure: A.L. Sheehan: None. J. O'Malley: None. S. Gunawan: None. S. Natarajan: None. G. Laynor: None. A. Nicholson: None. N. Illenberger: None.