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.