Type 1 diabetes results from autoimmune destruction of insulin-producing pancreatic β cells. The 60 kDa heat-shock protein (hsp60) is one of the known target self antigens. An immunomodulatory peptide from hsp60, p277, arrested β-cell destruction and maintained insulin production in newly diabetic NOD mice. We did a randomised, double-blind, phase II study of peptide treatment in patients with newly diagnosed (<6 months) type 1 diabetes.

35 patients with type 1 diabetes and basal C-peptide concentrations above 0·1 nmol/L were assigned subcutaneous injections of 1 mg p277 and 40 mg mannitol in vegetable oil (DiaPep277; n=18) at entry, 1 month, and 6 months, or three placebo injections (mannitol in vehicle; placebo; n=17). The primary endpoint was glucagon-stimulated C-peptide production. Secondary endpoints were metabolic control and T-cell autoimmunity to hsp60 and to p277 (assayed by cytokine secretion). 31 patients completed 10 months of follow-up and were included in the intention-to-treat analysis.

At 10 months, mean C-peptide concentrations had fallen in the placebo group (n=16) but were maintained in the DiaPep277 group (n=15; 0·26 [SD 0·11] vs 0·93 [0·35] nmol/L; p=0·039). Need for exogenous insulin was higher in the placebo than in the DiaPep277 group (0·67 [0·33] vs 0·43 [0·17] U/kg; p=0·042). Haemoglobin A1c concentrations were low (around 7%) in both groups. T-cell reactivity to hsp60 and p277 in the DiaPep277 group showed an enhanced T‐helper‐2 cytokine phenotype. No adverse effects were noted.

Although this study was small, treatment of newly diagnosed type 1 diabetes with DiaPep277 seems to preserve endogenous insulin production, perhaps through induction of a shift from T-helper-1 to T‐helper‐2 cytokines produced by the autoimmune T cells.