Treatment of Monogenic Diabetes with HNF1A Gene Mutation (MODY3) — Autosomal Dominant Symptomatic Familial Diabetes

This protocol applies to patients with autosomal dominant symptomatic familial diabetes due to an HNF1A (MODY3) or HNF4A (MODY1) mutation, presenting with postprandial or progressive hyperglycaemia. These individuals carry a confirmed pathogenic heterozygous mutation and demonstrate characteristic sensitivity to sulphonylureas.

HNF1A-MODY is the most common form of monogenic diabetes that results in familial symptomatic diabetes; heterozygous HNF1A mutations are approximately 10 times more frequent than heterozygous HNF4A mutations. Both HNF1A-MODY and HNF4A-MODY are sensitive to sulphonylureas, which typically enable better glycaemic control than insulin — especially in children and young adults. Most affected individuals show progressive deterioration in glycaemic management and require pharmacological treatment.

The evidence-based first-line approach for this sulphonylurea-sensitive MODY subtype involves a low-dose sulphonylurea, initiated with careful attention to the starting dose in order to avoid hypoglycaemia. The complete regimen — including specific agent selection, starting dose strategy, and long-term maintenance protocol — is available in the full structured protocol below.

Dosing details and the full clinical algorithm are not shown here.