A small case series showed that drugs like tirzepatide (a dual GIP/GLP‑1 agonist) and other GLP‑1 agonists can dramatically lower blood sugar and cause big weight loss in people with a rare form of diabetes called MODY, even letting some stop insulin altogether.

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.