Safety and Effectiveness of Oral Glyburide Suspension in Neonatal Diabetes Mellitus: French Retrospective Cohort Study

Abstract Context Neonatal diabetes mellitus (NDM) is a rare condition usually related to an identifiable genetic cause. Sulfonylurea therapy can ensure metabolic control, obviating the need for insulin while also improving neurodevelopmental outcomes. An oral glyburide suspension (OGS; AMGLIDIA) designed for pediatric use was introduced recently to eliminate the drawbacks of using crushed tablets. Objective To evaluate the long-term effectiveness and safety of the OGS for NDM. Design Retrospective cohort study. Setting Fifteen centers in France. Patients Consecutive patients started on OGS for NDM in 2015 through 2024. Intervention OGS therapy. Main outcome measures Glycated hemoglobin (HbA1c) values during OGS therapy; growth; and serious adverse events. Results Of 27 patients, 22 had KCNJ11 mutations, 4 had ABCC8 mutations, and 1 had a 6q24 anomaly. Median follow-up during OGS therapy was 2.7 years (range, 2 months–9 years). At baseline, median HbA1c was 6.5% (5.8–7.9) overall and 6.5%, 6.4%, and 8.9% in the KCNJ11, ABCC8, and 6q24 subgroups, respectively. The median starting glyburide dose was 0.15 mg/kg/day (range, 0.1-0.185). HbA1c decreased nonsignificantly over time in all subgroups (P = .382), prompting in a small OGS dosage decrease. The last recorded HbA1c value was 6.3%, 5.9%, and 7.4% in the KCNJ11, ABCC8, and 6q24 subgroups, respectively. Serious adverse events were rare, with hypoglycemia in 2 patients during periods of decreased food intake and diarrhea in 1 patient. Conclusion The OGS was effective in maintaining excellent metabolic control in the long term. The safety profile was good. The OGS should be considered for the first-line treatment of NDM.