Replacing C-Peptide in Type 1 Diabetes Improved Nerve Function in a Randomized Controlled Trial

C-peptide replacement therapy for 6 months improved sensory nerve conduction velocity (SCV) in type 1 diabetic patients with neuropathy. Both dose groups (1.5 mg/day and 4.5 mg/day) showed similar improvement. In the less severely affected patients (SCV < 2.5 SD below normal at baseline, n=70), SCV improved by 1.0 m/s compared to placebo (p<0.014). The proportion of patients showing SCV improvement >1.0 m/s was significantly greater in C-peptide groups versus placebo (p<0.03). Clinical neurological impairment scores and vibration perception also improved (p<0.011 and p<0.002 respectively). These improvements occurred independently of blood sugar control, which changed similarly across all groups.

Exploratory, double-blinded, randomized, placebo-controlled trial at five centers in Sweden. 139 type 1 diabetes patients with peripheral neuropathy completed the protocol. Three groups: C-peptide 1.5 mg/day (replacement dose, four subcutaneous injections daily), C-peptide 4.5 mg/day (3× replacement), or placebo. Neurological examination and neurophysiological measurements (nerve conduction velocity, vibration perception, clinical impairment scores) were performed at baseline and 6 months.

Diabetic neuropathy is the most common complication of type 1 diabetes, causing numbness, pain, and loss of sensation in the extremities, with no approved disease-modifying treatment. C-peptide — a natural byproduct of insulin production that is completely absent in type 1 diabetes — showed the ability to actually improve nerve function, not just slow deterioration. This is the first randomized controlled trial showing that replacing a missing peptide can reverse neuropathy damage.

For decades, C-peptide was considered biologically inert — just a byproduct of insulin production. This trial is part of the evidence that overturned that view, showing C-peptide has its own biological functions, particularly in protecting nerves and blood vessels. Despite promising results, C-peptide replacement has not reached FDA approval, partly due to the commercial challenges of developing a therapy for a relatively small patient population. The story of C-peptide illustrates how a 'waste product' peptide can turn out to have important therapeutic potential.

Described as 'exploratory,' suggesting it was powered for signal detection rather than definitive efficacy. The four-times-daily injection regimen is burdensome. The higher dose (4.5 mg/day) didn't show greater benefit than the replacement dose, raising questions about the dose-response relationship. Six months may be too short to see full nerve regeneration effects. The study was published in 2007, and C-peptide has not progressed to approval despite these promising results.