Cyclosporin and methotrexate therapy induces remission in type 1 diabetes mellitus.

Cyclosporin and methotrexate administration induces remission of type 1 diabetes mellitus. Administration of high-dose cyclosporin (cyclo) has been demonstrated to induce remission of type 1 diabetes mellitus (T1D). Its usefulness was limited by its toxicity. Since methotrexate (mtx) and cyclo synergistically inhibit autoimmune processes, we postulated that low doses of cyclo and mtx could safely induce remission of T1D. In a pilot study, insulin dose requirements and glycemic control were compared in 10 new onset T1D control children with seven children who were administered cyclo at 7.5 mg/kg/day for 6 weeks and then 4 mg/kg/day in addition to mtx 5 mg/kg/wk for 1 year. After 6 weeks, cyclo doses were adjusted to maintain blood cyclo levels 110-220 ng/ml. All children were treated with two daily injections of insulin. Clinical and biochemical toxicity of drug therapy was assessed. There were only very minor adverse effects and no drug induced biochemical test abnormalities. Mean HbA1c levels were similar in the experimental and control groups at baseline and at 3, 6, and 9 months but was lower in the cyclo + mtx group at 12 months. Daily insulin requirements of the groups were similar at baseline but lower in the cyclo + mtx group at 3, 6, 9, and 12 months. Although no control subjects became non-insulin requiring, four of seven cyclo + mtx-treated subjects were entirely off insulin therapy for 2.5, 4.5, 8, and 12 months. Low-dose cyclo and mtx treatment of subjects with new onset T1D can safely induce remission of disease and decrease the amount of required insulin.