ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes

This phase 2 clinical trial, conducted by Michael Brines and Anthony Cerami (the developers of ARA 290), evaluated the effects of the peptide in patients with type 2 diabetes mellitus complicated by neuropathy. Participants received daily subcutaneous injections of ARA 290 at a dose of 4 mg for 28 days, with detailed metabolic and neurological assessments.

The metabolic results were surprisingly positive: there was a significant reduction in glycated hemoglobin (HbA1c), indicating improvement in sustained glycemic control. Additionally, improvement was observed in the lipid profile, including triglyceride reduction. These metabolic effects were unexpected, as the study was originally designed to primarily assess neuropathic symptoms.

In the neurological assessment, treated patients showed improvement in neuropathic symptoms measured by the PainDetect questionnaire and by corneal confocal microscopy, which demonstrated partial recovery of corneal nerve fiber density — an objective marker of small fiber regeneration. This dual action (metabolic and neuroprotective) differentiates ARA 290 from conventional therapies for diabetic neuropathy.

The study is particularly relevant for demonstrating that ARA 290 simultaneously addresses the cause (hyperglycemia) and the consequence (neuropathy) of diabetes through activation of the tissue repair receptor. The favorable safety profile and absence of erythropoietic effects reinforced the therapeutic potential of the peptide for diabetic complications.