What are the treatments for each type of Maturity-Onset Diabetes of the Young (MODY)?

From the Guidelines

Treatment for Maturity-Onset Diabetes of the Young (MODY)

MODY treatment varies significantly depending on the subtype.

• GCK-MODY (MODY-2) typically requires no pharmacological treatment, with management focused on lifestyle modifications 1.
• HNF1A-MODY (MODY-3) and HNF4A-MODY (MODY-1) usually respond well to low doses of sulfonylureas, which are considered first-line therapy 1.
• HNF1B-MODY (MODY-5) may require treatment with insulin or oral hypoglycemic agents, such as metformin, due to the associated risk of pancreatic exocrine dysfunction 1.
• KCNJ11-related neonatal diabetes will exhibit improved glycemic control when treated with high-dose oral sulfonylureas instead of insulin 1.
• INS gene mutations are typically managed with intensive insulin management 1.
• GATA6, EIF2AK3, and FOXP3-related diabetes often require insulin therapy due to the severity of the disease and associated complications 1.

It is essential to note that a diagnosis of MODY allows for more cost-effective therapy and can lead to the identification of other affected family members 1. Therefore, a diagnosis of MODY should be considered in individuals with atypical diabetes and a family history of diabetes not characteristic of type 1 or type 2 diabetes 1.

From the Research

Treatment Options for MODY

The treatment for Maturity-Onset Diabetes of the Young (MODY) varies depending on the subtype. The main subtypes of MODY and their treatments are:

• GCK-MODY (MODY 2): No specific treatment is required, as patients with GCK mutations have a mild, asymptomatic, and stable fasting hyperglycemia 2, 3, 4, 5.
• HNF1A-MODY (MODY 3) and HNF4A-MODY (MODY 1): Patients with these subtypes usually respond well to sulfonylurea therapy, but may require insulin therapy as the disease progresses 2, 3, 4, 5.
• HNF1B-MODY (MODY 5): This subtype is associated with pancreatic agenesis, renal abnormalities, genital tract malformations, and liver dysfunction, and its treatment is not well established 4.
• Other subtypes of MODY: The remaining subtypes of MODY have a much lower prevalence, and very little data are available on their treatment 2, 4.

Novel Treatment Options

Newer blood glucose-lowering therapies, such as SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists, have been proposed as alternative treatments for MODY patients, especially those with HNF1A and HNF4A mutations 3.

• SGLT2 inhibitors: May be effective in reducing blood glucose levels in MODY patients with a lower risk of hypoglycemia and weight gain 3.
• DPP-4 inhibitors: May be effective in reducing blood glucose levels in MODY patients with a lower risk of hypoglycemia and weight gain 3.
• GLP-1 receptor agonists: May be effective in reducing blood glucose levels in MODY patients with a lower risk of hypoglycemia and weight gain 3.

Management Guidelines

Proper management guidelines during pregnancy have been developed for carriers of GCK gene mutations, but such guidelines are still a subject of debate in other cases, although some recommendations are available 2, 5.

• Pregnancy management: Carriers of GCK gene mutations require special management during pregnancy to prevent complications 2, 5.
• Genetic counseling: Accurate diagnosis of MODY allows for proper genetic counseling and early diagnosis for family members 2, 4, 5.