Slowed Metabolic Decline after One Year of Oral Insulin Treatment among Individuals at High Risk for Type 1 Diabetes in the Diabetes Prevention Trial-Type 1 and TrialNet Oral Insulin Prevention Trials

We assessed whether oral insulin slowed metabolic decline after 1 year of treatment in individuals at high risk for type 1 diabetes. Two oral insulin trials that were negative overall with type 1 diabetes as the primary endpoint were analyzed: the Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet oral insulin trials. Oral glucose tolerance tests at baseline and after 1 year of treatment were analyzed. Among those at high risk [Diabetes Prevention Trial Risk Score (DPTRS)≥6.75], the AUC C-peptide increased significantly from baseline to 1 year in each oral insulin group, whereas AUC glucose increased significantly in each placebo group. At 1 year, AUC C-peptide/AUC glucose was significantly higher (p<0.05) in the oral insulin group than in the placebo group in each trial (p=0.057 with age adjustment in the TrialNet trial; p<0.01 for trials combined with or without age adjustment). For DPTRS<6.75, oral insulin groups did not differ from placebo groups. The findings suggest that 1 year of treatment with oral insulin slows metabolic deterioration in individuals at high risk for type 1 diabetes. Moreover, the findings further suggest that metabolic endpoints can be useful adjuncts to the diagnostic endpoint in assessments of preventive treatments for the disorder.