SAT085 Oral Glucagon-like Peptide-1 Receptor Agonist As Adjuvant Treatment In HNF1A-MODY

Abstract

Abstract Disclosure: D.T. Broome: Grant Recipient; Self; NIH U54DK118612-04. Research Investigator; Self; Fractyl Laboratories, Novo Nordisk. Maturity-onset diabetes of the young (MODY) is an inherited form of monogenic diabetes caused by a mutation in a single gene. HNF1A-MODY is the most common treatment-requiring form of MODY with a reported frequency of 1.2%1. Early genetic diagnosis leads to more precise treatment, and sulfonylureas have been recognized as first-line treatment in patients with HNF1A-MODY. Although sulfonylurea treatment is often effective early in the disease course, patients often experience sulfonylurea treatment failure. As a result, there has been recent investigation into additional treatment options that are effective. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have previously been published for use in patients with HNF1A-MODY2,3, and recognized as a potential effective treatment in patients with HNF1A-MODY. Although GLP-1 RAs have been reported for use as injectable agents, there is currently no evidence reporting their effectiveness as oral medications. In this report, we present a novel case of use of oral semaglutide as adjuvant treatment to sulfonylurea in a patient with HNF1A-MODY. A 48-year-old female with a history of diabetes since age 22, later confirmed as HNF1A-MODY at age 45 (Heterozygous HNF1A mutation, c.608G>A (p.Arg203His), NM_000545.5), was glimepiride for 3 years and without micro- or macrovascular complications. She developed a 15-lb weight gain, and her HbA1c increased to 7% (HbA1c gradually increasing from 5.4% to 7.0% over 3 years) despite her taking glimepiride 4 mg twice daily prescribed by her primary care physician. Thereafter, her primary care physician prescribed oral semaglutide 3 mg once daily for 4 weeks, which was titrated to 7 mg once daily. After initiation of oral semaglutide, her glimepiride was reduced to 2 mg once daily, her HbA1c improved to 5.4%, and she lost 30 lbs over a 6-month timeframe. This is the first report demonstrating the benefits of oral GLP-1 RA treatment in a patient with HNF1A-MODY, and this clinical case provides further support of use GLP-1 RA use as adjuvant treatment to sulfonylurea in patients with HNF1A-MODY.