In six patients with genetically confirmed MODY, GLP-1 and dual GIP/GLP-1 receptor agonists reduced HbA1c by 1.0-4.1 percentage points, decreased weight by 2.6-29 kg, and allowed three of four insulin-treated patients to stop insulin.
3/4 stopped insulinThree of four insulin-treated MODY patients were able to discontinue insulin after starting incretin-based peptide therapy, while maintaining improved glycemic control
What the researchers found
All six MODY patients (5 with HNF1A variants, 1 with PAX4/PDX1 variants) showed improvement on incretin-based therapy:
- HbA1c reductions: 1.0-4.1 percentage points (from baseline range 7.3-10.6%)
- Weight loss: 2.6-29 kg (from baseline BMI range 25.1-36.7 kg/m²)
- Three of four insulin-treated patients discontinued insulin entirely
- Two insulin-naïve patients maintained good glycemic control without needing insulin
This is notable because HNF1A-MODY patients are known to have enhanced sensitivity to incretins due to their genetic variant's effect on beta cell function.
Why it matters
MODY affects about 1-2% of all diabetes cases and is frequently misdiagnosed as type 1 or type 2 diabetes. Current treatments (sulfonylureas, insulin) have limitations including weight gain and hypoglycemia risk. This case series suggests GLP-1 receptor agonists could offer a better treatment option — improving blood sugar, promoting weight loss, and potentially eliminating the need for insulin injections.
How the study worked
Retrospective case series at Tawam Hospital (2019-2024) including patients with genetically confirmed MODY who received GLP-1 receptor agonist or dual GLP-1/GIP receptor agonist treatment for at least three months. Clinical data (HbA1c, BMI, insulin use) were extracted from medical records.
What this study cannot tell us
Very small case series (n=6) without a control group. Retrospective design with potential selection bias (only patients who tolerated treatment are reported). Published in Cureus, which has variable peer review standards. The specific GLP-1RA and dual agonist used are not named in the abstract. Duration of follow-up varied. Results may not generalize to MODY caused by other gene variants.
How to read the evidence
This is a retrospective case series of six patients — the lowest level of clinical evidence. While the results are striking (insulin discontinuation, large HbA1c reductions), the very small sample size, lack of controls, and retrospective design mean these findings require prospective validation before influencing practice guidelines.
When this study was published
Published in 2025, this case series represents early clinical experience with incretin therapies in MODY — a novel application that has not been widely studied.
The bigger picture
This case series opens a new frontier for incretin peptide therapy in monogenic diabetes. HNF1A-MODY patients may be particularly good candidates because their genetic defect enhances incretin sensitivity — these patients could respond to GLP-1 agonists even better than typical type 2 diabetes patients. As genetic testing becomes more common, personalized peptide therapy based on specific diabetes genotypes could become reality.
Questions still open
- Should all HNF1A-MODY patients be considered for GLP-1 receptor agonist therapy as first-line treatment?
- Do dual GIP/GLP-1 agonists (tirzepatide) outperform single GLP-1 agonists in MODY?
- Could genetic MODY subtyping predict which patients will respond best to incretin-based therapies?
Common questions
What is MODY and how is it different from regular diabetes?
Why might GLP-1 drugs work especially well for MODY?
Read the original research
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).
Cureus, 17(10), e94882
Citation
Hilal, Abdalla; Afandi, Bachar; Almazrouei, Raya. (2025). 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).. Cureus, 17(10), e94882. https://doi.org/10.7759/cureus.94882