Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study

Study (n=81) found that after a median follow-up of 10.2 years, good glycaemic control was maintained on a sulfonylurea alone (median HbA1c 8.1% before transfer to sulfonylurea, 5.9% at 1 year, and 6.4% at most recent follow-up). There were no reports of severe hypoglycaemia.

A related editorial discusses this research.  The evidence that HbA1c is improved by sulfonylurea treatment more than with insulin is robust, and the results of this study, together with previous research, show that hypoglycaemia is mild and other side-effects of high-dose sulfonylureas are not clinically significant. Some evidence exists that sulfonylurea therapy might have a beneficial effect on the neurological features seen in patients with more severe mutations, but treatment might need to start at an early age and the benefit might be small. This study reports that, despite some initial improvement in some patients, neurological features persisted in their international cohort of long-term sulfonylurea-treated patients.

 

Overall, the fact that this study illustrates the durability of sulfonylurea therapy without substantial off-target effects will be of general interest, not only to those following advances in this field, but as an exemplar of precision medicine. These results also suggest that there are important differences between sulfonylurea therapy in type 2 diabetes and neonatal KATP-related diabetes, the mechanisms of which remain to be fully elucidated.