ABSTRACT Permanent neonatal diabetes mellitus (PNDM) is commonly caused by pathogenic variants in KCNJ11 that impair insulin secretion through ATP‐sensitive potassium (K ATP ) channel dysfunction. Sulfonylureas (SUs) can stimulate insulin secretion and enable insulin discontinuation, but insulin withdrawal may remain difficult even under high‐dose SU, especially when therapy is initiated later in life. We describe a woman with KCNJ11 ‐related PNDM who achieved insulin discontinuation after adding sitagliptin, followed by further improvement with semaglutide during a five‐year follow‐up. HbA 1c remained between 6.1% and 6.5% on semaglutide 0.25 mg/week, with a 60% reduction in glibenclamide and preserved endogenous insulin secretion. A transient HbA 1c rise after semaglutide interruption, followed by improvement upon resumption, confirmed its reversible effect. No episodes of severe hypoglycemia or gastrointestinal adverse events occurred. This case suggests that combining insulin secretagogues targeting both K ATP ‐dependent (triggering: SU) and K ATP ‐independent (amplifying: incretin‐based therapy) pathways may provide additive or synergistic benefits in PNDM.
Ohkuma et al. (Tue,) studied this question.