A Case of Oral Semaglutide for Treatment of Hepatocyte Nuclear Factor 4A Maturity-Onset Diabetes of the Young.

BACKGROUND/OBJECTIVE: Maturity-onset diabetes of the young (MODY) is a form of autosomal dominant monogenic diabetes. Sulfonylureas are the mainstay of therapy for hepatocyte nuclear factor 4A (HNF4A) MODY. Here, we present a patient with HNF4A MODY successfully treated with oral semaglutide. CASE DESCRIPTION: A 58-year-old woman with diabetes presented for evaluation. Body mass index was 23.3 kg/m without signs of insulin resistance. Hemoglobin A1c was 6.1% on glipizide 5 mg daily and metformin 500 mg twice daily with fasting hyperglycemia in the morning and episodes of hypoglycemia.To decrease the frequency of hypoglycemia, her regimen was changed to glimepiride 1 mg daily and metformin 500 mg twice daily. Genetic testing results revealed HNF4A MODY, c.335G>A (p.Arg112GIn). Metformin was stopped and she switched to oral semaglutide 3 mg daily, increased to 7 mg daily after 30 days, and glimepiride 1 mg daily. After 3 months, glimepiride was discontinued due to hypoglycemia. Nine months after starting semaglutide and on monotherapy with semaglutide 7 mg daily, hemoglobin A1c was 5.7%, and her continuous glucose monitor reported 98% time in range with no episodes of hypoglycemia. DISCUSSION: To our knowledge, this is the first case of HNF4A MODY to be treated with oral semaglutide alone. Oral glucagon-like peptide receptor-1 receptor agonists may be used to treat HNF4A MODY as an independent or adjunctive therapy to sulfonylureas. Both medications work via different mechanisms to bypass the malfunctioning pathway caused by the HNF4A MODY variant. CONCLUSION: Glucagon-like peptide 1 receptor agonists, including oral semaglutide, may be safe and efficacious treatments for patients with HNF4A MODY.