Treatment Options for Patients with Maturity-Onset Diabetes of the Young (MODY): A Systematic Review of Literature:...

Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes characterized by impaired insulin secretion and genetic and clinical heterogeneity. Accurate molecular diagnosis enables precision medicine by guiding gene-specific treatment, improving glycemic control, and avoiding unnecessary therapies. Since our previous systematic review in 2020, new studies have further clarified therapeutic strategies and emerging treatment options. This review updates the evidence on pharmacological management of MODY and its clinical implications.

A systematic review was conducted following PRISMA 2020 recommendations. PubMed was searched for studies published between April 2020 and October 2025. Eligible studies included individuals with genetically confirmed MODY receiving pharmacological treatment, therapeutic switches, or adjunctive therapies. Data were extracted and synthesized qualitatively due to heterogeneity in study design and outcome reporting.

Ninety-one studies were included. Strong evidence confirms sulfonylureas (SUs) as first-line therapy in Hepatocyte Nuclear Factor 1A (HNF1A)-, Hepatocyte Nuclear Factor 4A (HNF4A)-, ATP-binding cassette transporter sub-family C member 8 (ABCC8)-, and potassium inwardly rectifying channel subfamily J member 11 (KCNJ11)-MODY, frequently enabling improved glycemic control and transition from insulin. Glucokinase (GCK)-MODY remains managed without pharmacological treatment outside pregnancy, but dorzagliatin, a novel agent acting as a glucokinase activator, may further expand precision treatment approaches. Insulin remains the mainstay of treatment in Hepatocyte Nuclear Factor 1B (HNF1B)- and Insulin (INS)-MODY, although adjunctive therapies may provide benefits. While SUs are supported by consistent observational evidence, the role of incretin-based therapies and sodium-glucose co-transporter 2 inhibitors remains exploratory, largely based on small studies and case reports.

A major limitation of the available evidence is the predominance of small, heterogeneous observational studies, which limits the strength and generalizability of therapeutic recommendations. Recent literature largely confirms existing genotype-guided treatment recommendations while suggesting expanded therapeutic options for selected MODY subtypes. Precision medicine based on molecular diagnosis remains essential for optimal management.