MON-130 Optimal Glycemic Control in a Patient with HNF1A MODY with GLP1-RA Monotherapy: Implications for Future Therapy

Abstract

Background: Among those diagnosed with maturity-onset diabetes of the young (MODY), the most common form is hepatocyte nuclear factor 1α MODY (HNF1A MODY). Individuals with HNF1A MODY typically respond very well to treatment with sulfonylureas (SU) which are recommended as first line therapy. Clinical Case: A 23 year old Caucasian woman with presumed type 1 diabetes since age 14 presented for diabetes care during pregnancy where she maintained an A1c between 5.9% - 7.5% on full basal-bolus insulin therapy. In the immediate post-partum period a diagnosis of MODY was suspected, despite no family history of diabetes, given frequent hypoglycemia on a low total daily dose of insulin of 0.2u/kg/day with minimal basal insulin requirement, absence of development of DKA in the setting of complete cessation of insulin for several days, random c-peptide 2.15 ng/mL (ref. range 0.80-3.10 ng/mL) with concurrent glucose 181mg/dl, and absent anti-GAD and islet cell antibodies. Genetic sequencing revealed a de novo heterozygous mutation for variant c.827C>A; p.Ala276Asp in exon 4 of the HNF1A gene consistent with HNF1A MODY. In 2014, insulin was discontinued and SU therapy was started with A1c ranging 7.1% - 8.8% in the setting of variable adherence. Given consistently elevated A1c, dulaglutide 0.75mg weekly was started in 2017 with subsequent improvement in glycemic control allowing a decrease in SU dose. In early 2018, she discontinued SU therapy entirely given frequent hypoglycemia on glimepiride 1mg daily and dulaglutide 0.75mg weekly. After SU discontinuation, dulaglutide was increased to 1.5mg weekly and her A1c improved to 6.6% without hypoglycemia, the best A1c of her adult life with the exception of during her pregnancy. Conclusion: There is little data on the use of GLP1-RA as monotherapy for patients with HNF1A MODY and no long term studies of GLP1-RA monotherapy or parallel group, head-to-head studies of GLP1-RA vs. SU have been published. In this case, dulaglutide monotherapy was more effective than glimepiride monotherapy in achieving short term glycemic targets in an individual with HNF1A MODY.