Incretin-based therapy enables insulin discontinuation and sulfonylurea reduction in KCNJ11-related permanent neonatal diabetes patient over five years

Permanent neonatal diabetes mellitus (PNDM), particularly that caused by KCNJ11 pathogenic variants, results from impaired insulin secretion due to ATP-sensitive potassium (KATP) channel dysfunction. While sulfonylureas (SUs) can stimulate insulin secretion by targeting these channels, enabling insulin discontinuation, long-term management can be challenging, and insulin withdrawal may not always be sustained or optimal. There's a need for therapies that can provide stable glycemic control and reduce reliance on traditional insulin or high-dose SUs in this specific genetic subtype.

This study presents a five-year follow-up of a single patient diagnosed with KCNJ11-related permanent neonatal diabetes mellitus (PNDM). The patient received incretin-based therapy, which included either DPP-4 inhibitors (such as sitagliptin, vildagliptin, or saxagliptin) or GLP-1 analogs (such as exenatide or liraglutide), used alone or in combination with other anti-diabetic drugs. The primary objective was to evaluate the long-term efficacy of this regimen in achieving and maintaining insulin discontinuation and reducing sulfonylurea dosage.

Over a five-year follow-up period, the patient with KCNJ11-related PNDM successfully transitioned from insulin therapy. The introduction of incretin-based drugs, including both DPP-4 inhibitors and GLP-1 analogs, facilitated a significant improvement in glycemic control. This allowed for the complete discontinuation of exogenous insulin, a critical outcome for patients with PNDM. Furthermore, the long-term use of these incretin therapies also enabled a substantial reduction in the required dosage of sulfonylureas. This sustained therapeutic effect highlights the potential of incretin-based approaches to modulate the underlying pathophysiology in KCNJ11-related diabetes. The patient maintained stable glycemic parameters throughout the follow-up, demonstrating the durability of the treatment strategy. This case provides compelling evidence for the efficacy of incretin-based therapies in managing this rare genetic form of diabetes.

The patient achieved complete insulin discontinuation and a significant reduction in sulfonylurea dosage, maintained over a five-year period.