Metformin Use Is Associated With Reduced Rates of Primary Nerve Decompression Surgery and Revision in Type 2 Diabetes: A Retrospective Cohort Study

Purpose Type 2 diabetes mellitus is a risk factor for compressive neuropathy. The purpose of this study was to determine whether metformin use is associated with reduced rates of compressive neuropathy, primary nerve decompression surgery, and revision after carpal tunnel release and cubital tunnel release, while controlling for concurrent diabetes medications. Methods We performed a retrospective cohort study using the TriNetX federated research network. Adults with type 2 diabetes mellitus were stratified by metformin exposure, defined as at least 10 prescriptions over 5 years. The primary outcomes were incident compressive neuropathy and nerve decompression surgery. In a unilateral revision cohort, the outcome was ipsilateral revision between 30 days and 5 years after the index procedure. One-to-one propensity score matching balanced cohorts on demographics, comorbidities, and concurrent diabetes medications. Four prespecified medication-stratified sensitivity analyses addressed insulin, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists. Carpal tunnel release and cubital tunnel release revision results were pooled via fixed-effect meta-analysis. Results After matching, the primary analysis included 260,823 pairs. Metformin users had lower rates of nerve decompression surgery (0.60% vs 0.72%; odds ratio, OR, 0.831 [0.776–0.889]) and compressive neuropathy diagnosis (2.78% vs 3.05%; OR, 0.909 [0.879–0.941]). The surgery-level association was stronger without concurrent insulin (OR, 0.727 [0.662–0.799]) and attenuated to nonsignificance with concurrent insulin (OR, 0.948 [0.836–1.076]), though the diagnosis-level association persisted. Among patients with unilateral carpal or cubital tunnel syndrome, ipsilateral revision was less frequent in metformin users (pooled OR, 0.711 [0.533–0.950]). Metformin users also had lower vitamin B12 levels (mean, 646.4 vs 707.4 pg/mL), consistent with sustained metformin exposure. Conclusions Metformin use was associated with reduced incidence of nerve decompression surgery and ipsilateral revision after carpal tunnel release and cubital tunnel release in patients with type 2 diabetes mellitus, with directionally consistent effects across sensitivity analyses. These findings suggest that maintaining metformin therapy may carry benefit beyond glycemic control. Prospective studies are needed to validate these findings. Type of study/level of evidence Prognostic II.