Potential adjunctive therapies in adolescents with type 1 diabetes mellitus

Appropriate insulin therapy is central to the management of all individuals with type 1 diabetes mellitus. The potential role of adjunctive therapy in type 1 diabetes is to improve insulin action, and facilitate the ability of all individuals with type 1 diabetes to achieve and maintain 'better' metabolic control. The landmark clinical trial in type 1 diabetes is the Diabetes Control and Complications Trial (DCCT). The DCCT showed that there is no threshold below which a reduction in glycemia would not provide further benefit against diabetes-related microvascular complications. This study in particular provides the rationale for attempting to achieve as near normoglycemia as possible. We review the use of recognized pharmacologic agents as potential insulin adjunctives in children and adolescents with type 1 diabetes. Adjunctive therapies can be grouped into the following categories based on their putative mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin), and other targets of action (e.g. pirenzepine and insulin-like growth factor-1 [IGF-1], which reduce growth hormone secretion, and glucagon-like peptide-1, which acts to stimulate insulin secretion). Many of these agents have been found to be effective in short-term studies with decreases in glycosylated hemoglobin of 0.5-1.0%, lowered postprandial blood glucose levels, and decreased daily insulin doses. Adverse effects such as poor gastrointestinal tolerability (metformin, acarbose) or potential acceleration of retinopathy (IGF-1) indicates the need for further studies of efficacy, safety, and patient selection before these adjunctive therapies can be widely recommended in type 1 diabetes.