Metformin therapy modifies corneal neuroimmune abnormalities in people with type 2 diabetes

Aims/hypothesis

Diabetic peripheral neuropathy is a debilitating microvascular complication of diabetes mellitus, with limited disease-modifying therapies to date. This study aimed to assess the effect of metformin on the corneal sub-basal nerve plexus as a peripheral neuropathy outcome measure in people with type 2 diabetes.

Methods

A cohort of 36 participants with type 2 diabetes receiving metformin therapy were recruited and underwent clinical assessment, corneal confocal microscopy and nerve conduction studies. Concurrently, 36 participants with type 2 diabetes not receiving metformin therapy were selected as disease controls and matched to participants on metformin therapy for age, sex, diabetes duration, BMI, eGFR, HbA_1c, use of other oral glucose-lowering agents and therapies used for the treatment of the metabolic syndrome. Additionally, 25 healthy control participants were assessed and matched for age and sex. Medical record data over the previous 20 years were analysed for prior and current metformin use in all participants with type 2 diabetes.

Results

Participants receiving metformin therapy had higher corneal nerve fibre density (p=0.020), corneal nerve fibre length (p=0.020) and corneal fractal dimension (p=0.003) compared with those not receiving metformin therapy. The inferior whorl dendritic cell density was significantly lower in the metformin group compared with the non-metformin group (p=0.043).

Conclusions/interpretation

Metformin treatment is associated with superior corneal nerve parameters and neuroimmune tone in the corneal sub-basal nerve plexus. This study provides further evidence that metformin may be neuroprotective in diabetic peripheral neuropathy.

Graphical Abstract