Meglitinide Analogues in Adolescent Patients With HNF1A-MODY (MODY 3)

Abstract

For pediatric patients with hepatocyte nuclear factor-1A (HNF1A)-maturity-onset diabetes of the young (MODY 3), treatment with sulfonylureas is recommended. In adults with HNF1A-MODY, meglitinide analogues achieve lower postprandial glucose levels and pose a lower risk of delayed hypoglycemia compared with sulfonylureas. This therapy has not yet been reviewed in pediatric patients. We report on meglitinide analogue treatment in 3 adolescents with HNF1A-MODY. Case 1 (14-year-old girl) was diagnosed asymptomatically but had an hemoglobin A1c (HbA1c) level of 7.4%; her father had been recently diagnosed with HNF1A-MODY. With repaglinide, her HbA1c level decreased to 5.5%, with no hypoglycemic episodes. Case 2 (14-yearold boy) was diagnosed incidentally with glucosuria (HbA1c level: 7.0%) and was treated with insulin. After the HNF1A-MODY diagnosis, he was switched to glibenclamide. Due to several hypoglycemic episodes, treatment was changed to nateglinide and his HbA1c level decreased to 6.2% with no further hypoglycemic episodes. Case 3 (11-year-old girl) presented with polyuria and polydipsia (HbA1c level: 10.1%) and was initially treated with insulin. After the HNF1A-MODY diagnosis, treatment was changed to repaglinide. She was obese (BMI: 28.8 kg/m 2 ; z-score: +2.2), and glucose control with repaglinide alone was insufficient. Therefore, neutral protamine Hagedorn insulin (0.27 U/kg per day) was added. With this combination therapy, her HbA1c level decreased to 8.2%. The use of meglitinides in these 3 adolescent patients was well tolerated and effective. Furthermore, hypoglycemic episodes were rare compared with treatment with insulin or sulfonylureas. We therefore suggest considering meglitinides as the primary oral treatment option for adolescents suffering from HNF1A-MODY.

Monogenic Diabetes in Children and Adolescents: Recognition and Treatment Options

“…There is a published case report on the use of repaglinide and nateglinide in adolescents with HNF1A-MODY. In this study of three adolescents, use of meglitinides was associated with no or rare hypoglycemia compared to frequent hypoglycemia on SUs, suggesting that meglitinides could be the first-line therapy for adolescents with HNF1A-MODY, ahead of SUs [54]. …”

Successful maintenance on sulphonylurea therapy and low diabetes complication rates in a HNF1A–MODY cohort

“…Sulphonylureas have been shown to successfully bypass the major β–cell defects that result in HNF1A–MODY . The response to sulphonylureas in individuals with HNF1A–MODY has been investigated in a number of small studies . The specific therapeutic response to sulphonylureas in HNF1A–MODY was confirmed by a double‐blind randomized clinical study comparing the efficacy of gliclazide and metformin in HNF1A–MODY and Type 2 diabetes mellitus .…”

Use of oral antidiabetic drugs in the treatment of maturity‐onset diabetes of the young: A mini review

“…Tuomi et al demonstrated in 15 HNF1‐α MODY patients that nonsulphonylurea secretagogue nateglinide at very low doses (30 mg) prevents acute postprandial rises of glycaemia more effectively than the reference drug glibenclamide; moreover, it did so with a lower incidence of hypoglycaemia during lower peak levels of stimulated insulin. A small study involving 3 adolescent HNF1‐α MODY patients reported comparable efficacy of glinides to the reference treatment with sulphonylurea derivatives and insulin, as well as good tolerance and a better safety profile with a significantly lower risk of hypoglycaemia …”