Efficacy and safety of alogliptin in a pediatric patient with maturity-onset diabetes of the young type 1

Maturity-onset diabetes of the young (MODY) involves 1–2% of all diabetes cases. MODY is often diagnosed at a young age, and is characterized by autosomal dominant inheritance, non-obesity, sustained endogenous insulin secretion, and lack of β-cell autoimmunity (1,2,3). Among all MODY cases, MODY type 1 (MODY1) is rare and is caused by mutations of hepatocyte nuclear factor-4α (HNF-4α), which is a transcription factor expressed primarily in the liver, but also in the pancreas and kidneys, affecting glucose metabolism through a variety of routes (4). Fetal heterozygosity results in significant macrosomia due to increased insulin secretion in utero and subsequent neonatal transient or prolonged hypoglycemia (5). Glycosuria is not a feature of MODY1, and carriers are recognized to have decreased apolipoprotein levels (6). Endogenous insulin secretion is maintained in an early stage, and sulfonylureas (SUs) are recommended as the first-line treatment for MODY1 patients. However, insulin production is progressively reduced because of a continuous loss of β-cell function, and eventually patients with MODY 1 require insulin treatment. Dipeptidyl peptidase-4 (DPP-4) inhibitors augment glucose-dependent insulin secretion and suppress glucagon levels through enhancement of the action of endogenous incretin by inhibiting DPP-4, an incretin-degrading enzyme. DPP-4 inhibitors are generally well tolerated because of their low risk of hypoglycemia and other adverse events. Moreover, with their potential to improve β-cell function, a core defect of type 2 diabetes, DPP-4 inhibitors are becoming a major component of the treatment of type 2 diabetes in adults (7). Alogliptin (Takeda Inc., Osaka, Japan) is a highly selective DPP-4 inhibitor, and a once daily oral administration of alogliptin has a potential glucose-lowering effect, which is similar to that of other DPP-4 inhibitors, with a low risk of hypoglycemia and of weight gain (8). We encountered a 13-yr-old Japanese girl with diabetes who had marked hyperglycemia and who was initially treated with insulin. She was finally diagnosed as having MODY1 via gene analysis, and her treatment was then changed to the DPP-4 inhibitor alogliptin. Monotherapy with alogliptin was successful for glycemic control. We hereby report the efficacy and safety of alogliptin for the treatment of MODY1 in a pediatric patient.