1875-LB: Adjuvant Glucagon-Like Peptide 1 Receptor Agonist (GLP-1 RA) Use in HNF1A- and HNF4A-MODY

Introduction: Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of monogenic diabetes. Although sulfonylurea treatment is effective early in the disease course for HNF1A-MODY and HNF4A-MODY, patients often experience sulfonylurea treatment failure. Glucagon-like peptide-1 Receptor Agonists (GLP-1 RA) have previously been used in HNF1A-MODY and HNF4A-MODY, but there is a lack of evidence for their effectiveness as adjuvant treatment. Methods: We compiled a case series study of University of Michigan MODY patients to examine the effect of adjuvant GLP-1 RA treatment in patients with HNF1A-MODY and HNF4A-MODY treated with sulfonylureas. Results: Of 87 patients with genetically confirmed MODY (76 HNF4A-MODY, 11 HNF1A-MODY), there were 4 patients identified who were treated with a GLP-1 RA as adjuvant treatment to a sulfonylurea. All patients were White, 3 were female, 3 had HNF1A-MODY and all patients were from different pedigrees. The average HbA1c prior to initiation of GLP-1 RA was 7.7 u+/u 0.4%, and the average BMI was 28.5 kg/m2. After GLP-1 RA initiation, there was an average decrease in HbA1c of 1.3 u+/u 0.4%, with an average body weight loss of 15.8 u+/u 10.7 lbs (BMI change of -2.6 kg/m2). Patients had the following information (sex, current age, mutation, sulfonylurea dose reduction, administration F, 55, HNF1A-MODY, glipizide 5 mg/day reduction, subcutaneous dulaglutide, 1.5 mg once weekly, 21.5 mos.; 56, F, HNF1A-MODY, glipizide 10 mg/day reduction, subcutaneous semaglutide, 0.5 mg once weekly, 24 mos.; 43, M, HNF4A-MODY, glipizide 10 mg/day reduction, subcutaneous dulaglutide, 1.5 mg once weekly, 47.5 mos. Conclusions: These 4 patients (3 HNF1A-MODY, 1 HNF4A-MODY) demonstrate that adjuvant treatment with GLP-1 RA lowers HbA1c, body weight, and sulfonylurea dose requirements in patients with HNF1A- and HNF4A-MODY. Disclosure D. Broome: Research Support; Novo Nordisk, Fractyl Health, Inc., Rhythm Pharmaceuticals, Inc., T1D Exchange. Consultant; Tayco, Inc. M.C. Foss-Freitas: Research Support; Amryt Pharma Plc. Advisory Panel; PTC Pharmaceuticals. C. Chase: None. B. Gregg: Consultant; CVS Caremark. E.A. Oral: Consultant; Akcea Thearpeutics, Inc. Research Support; Akcea Thearpeutics, Inc. Consultant; Regeneron Pharmaceuticals Inc. Research Support; Regeneron Pharmaceuticals Inc., Amryt Pharma Plc. Consultant; Amryt Pharma Plc, Ionis Pharmaceuticals. Research Support; Ionis Pharmaceuticals, Rhythm Pharmaceuticals, Inc., Novo Nordisk, GI Dynamics, Fractyl Health, Inc. W.H. Herman: Consultant; Merck Sharp American Diabetes Association. Other Relationship; National Institutes of Health. Advisory Panel; National Committee for Quality Assurance.