# Novel Use of Glucagon-Like Peptide-1 (GLP-1) and Dual Glucose-Dependent Insulinotropic Polypeptide (GIP)/GLP-1 Receptor Agonists in Maturity-Onset Diabetes of the Young (MODY)

## TL;DR

This study shows that GLP-1 and dual GIP/GLP-1 receptor agonists can improve blood sugar control and reduce weight in patients with MODY, a genetic form of diabetes.

## Contribution

The novel contribution is the first reported use of GLP-1 and dual GIP/GLP-1 receptor agonists in treating MODY, particularly in patients with HNF1A and PAX4/PDX1 variants.

## Key findings

- GLP-1 and dual GIP/GLP-1 agonists significantly reduced HbA1c levels in MODY patients.
- Treatment led to weight loss and reduced insulin dependency in most patients.
- Patients with HNF1A and PAX4/PDX1 variants showed consistent improvement in glycaemic control.

## Abstract

Introduction

Maturity-onset diabetes of the young (MODY), particularly due to HNF1A variants, is usually treated with sulfonylureas or insulin. In patients with excess weight or poor glycaemic control, these approaches can be challenging. Incretin-based therapies may provide a safer and more effective alternative.

Methods

We conducted a retrospective case series at Tawam Hospital (2019-2024), including patients with genetically confirmed MODY who received a Glucagon-like peptide-1 (GLP-1) receptor agonist or dual GLP-1/Glucose-dependent insulinotropic polypeptide (GIP) receptor agonist for at least three months. Clinical data, including HbA1c, body mass index (BMI), and insulin use, were extracted from medical records. The primary outcome was change in HbA1c; secondary outcomes included changes in BMI and insulin requirements.

Results

Six patients were included (five with HNF1A variants, one with combined PAX4/PDX1 variants). At baseline, HbA1c ranged from 7.3% to 10.6% and BMI from 25.1 to 36.7 kg/m². Following treatment, HbA1c improved in all cases (reductions of 1.0-4.1 percentage points) and weight decreased by 2.6-29 kg. Three of four insulin-treated patients discontinued insulin, while insulin-naïve patients maintained good glycaemic control without insulin initiation.

Conclusion

GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists improved glycaemic control, reduced body weight, and decreased insulin dependency in MODY patients. These findings suggest incretin-based therapies may be a safe and effective option in selected genotypes, meriting further evaluation in prospective studies.