Skip to main content
ENDO 2026 Main banner

Diabetes and Vascular Disease

SUN-549 - GLP-1 RA and Dual GIP/GLP-1 RA in HNF1A-MODY and HNF4A-MODY: An Observational, Cross-Sectional Analysis of the Precision Diabetes Consortium (PREDICT)

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Rochelle N. Naylor, MD: No financial relationships to disclose
Elif A. Oral, MD: No relevant disclosure to display


Introduction: Maturity Onset Diabetes of the Young (MODY) is a monogenic and non-autoimmune form of diabetes mellitus that accounts for 0.4% of all cases of diabetes and 1-5% of young onset diabetes cases (1). Individuals with HNF1A-MODY and HNF4A-MODY are typically treated initially with sulfonylureas (SUs), to which many respond well early in the disease course. However, SU use can be limited by the high risk of hypoglycemia. Additionally, efficacy of SU often declines over time due to progressive β-cell dysfunction, leading to the use of insulin therapy with increased risk of hypoglycemia. Consequently, interest has grown in insulin-sparing therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dual glucose insulinotropic polypeptide (GIP)/GLP-1 RA. The clinical effectiveness of GLP-1 RA and dual GIP/GLP-1 RA in larger and well-characterized cohorts of individuals with HNF1A-MODY and HNF4A-MODY remains unknown.
Research Design &

Methods: We conducted an observational cross-sectional analysis of individuals with HNF1A-MODY and HNF4A-MODY enrolled in PREcision Diabetes ConsorTium (PREDICT) data commons who were treated with GLP-1 RA or dual GIP/GLP-1 RA. HbA1c, body mass index (BMI), and SU dose were compared before and after therapy using two-tailed paired t tests with a prespecified alpha of 0.05. Analyses were performed using IBM SPSS Statistics for Windows version 27 (IBM Corp., Aramonk, N.Y., USA).

Results: Twenty-three individuals with HNF1A-MODY (n=16) and HNF4A-MODY (n=7) who were treated with GLP-1 RA or dual GIP/GLP-1 RA were identified. Among those treated with GLP-1 RA (n=19) for a median duration of 34.9 months (Q1 10.3, Q3 42.5, IQR 32.2), there was a statistically significant reduction in HbA1c by 1.1% (p < 0.001), a BMI reduction of 2.4 kg/m2 (p=0.002), and a reduction in SU dose by 70.1% (p < 0.001). Six individuals were treated with a dual GIP/GLP-1 RA treatment including one transitioned from GLP-1 RA to dual GIP/GLP-1 RA. Median treatment duration was 25.3 months (Q1 10.0, Q3 34.9, IQR 24.9). Dual therapy was associated with a statistically significant decrease in HbA1c of 2.0% (p < 0.001), a reduction in BMI of 5.2 kg/m2 (p=0.011), and a 77.5% reduction in SU (p =0.002).

Conclusions: In individuals with HNF1A- and HNF4A-MODY, GLP-1 RA and dual GIP/GLP-1 RA therapy was associated with meaningful improvements in glycemic control, reductions in BMI, and substantial decreases in sulfonylurea requirements. These findings support incretin-based therapies as promising options in treatment-requiring MODY and warrant confirmation in prospective, genotype-specific randomized trials.

References:
1). Shields BM, Shepherd M, Hudson M, et al. Population-Based Assessment of a Biomarker-Based Screening Pathway to Aid Diagnosis of Monogenic Diabetes in Young-Onset Patients. Diabetes Care. 2017;40(8):1017-1025. PMID: 28701371. PMCID: PMC5570522.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*