Non-Insulin pharmacological treatment
Though insulin is the mainstay of treatment of DIDM, other pharmacological agents has been tried in the past with variable success. Metformin has been suggested to be safe and reasonably effective in a retrospective analysis (51) where 17 children with DIDM on ALL directed therapy, required metformin for median 6 days (range-246 days), with dose ranging from 100-2000 mg/day. Twelve patients didn’t require insulin for sugar control. Seelig E. et al(52) in their randomized controlled trial on adult patients receiving steroids for various indications showed normally maintained median glucose by 2- hour area under curve (AUC) during oral glucose tolerance test after 4 weeks of steroid therapy along with metformin unlike control patients. Another recent trial(53) demonstrated metformin could prevent dysglycemia in adults with cancer. So, metformin looks an attractive alternative/addition to insulin, as it is not associated with discomfort of pricks by insulin administration and sugar monitoring lancets, with reduced risk of hypoglycemia. In addition, advantages not related to glycemic control has been suggested i.e. beneficial effect in malignancy due to m-TOR inhibition and protection from anthracycline cardiotoxicity(54)(55)(56). Limitations of metformin administration for hyperglycemia management in ALL are lack of strong evidence of efficacy, difficulty in rapid titration of doses as per sugar levels and concerns regarding its side effect profile in critically ill children. Further larger prospective studies are necessary to address these concerns.
Recently, Glucagon Like Peptide-1 (GLP-1) agonist, exenatide has been shown to be effective in prevention of steroid induced glucose intolerance and beta cell dysfunction in healthy adults (57). More evidence is required to use this drug in drug induced hyperglycemia setting. Other oral antidiabetic drugs i.e. sulfonylureas, thiazolidinediones, DPP-4 inhibitors, meglitinides etc. has been tried in adults with steroid induced hyperglycemia. But use of these drugs in DIDM during pediatric ALL therapy has not been approved, so detailed discussion in context of DIDM is beyond the scope of this article.