122-OR: Impact of Withdrawal of Interventions in the Restoring Insulin Secretion (RISE) Pediatric Medication Study

Abstract

The RISE Pediatric Medication Study showed, in 91 obese 10-19 yo youth with impaired glucose tolerance (IGT, 60%) or recent-onset type 2 diabetes (T2D, 40%), that 12 mo of intervention with metformin alone (M) or glargine for 3 mo followed by metformin for 9 mo (G+M) resulted in no change in BMI or HbA1c and a decline in β-cell function measured by hyperglycemic clamp. These outcomes worsened 3 mo after withdrawal of the interventions. We expand our findings to mo 21 (M21) post randomization (9 mo after withdrawal of M or G+M) using oral glucose tolerance test (OGTT) measures of β-cell responsiveness (C-peptide index, CPI; insulinogenic index, IGI; incremental C-peptide/glucose area under the curve), BMI and HbA1c. Paired t-tests were used to compare treatment groups on changes from baseline (BL, n=91) to mo 12 (M12, n=86) and M21 (n=82), and from treatment withdrawal at M12 to M21. At M12 vs. BL, no measures differed in either group (Table). At M21 vs. BL, HbA1c increased in both groups, and BMI increased and CPI and IGI declined in the G+M group. At M21 vs. M12, BMI, HbA1c, fasting and 2-h glucose increased in both groups, and CPI declined in the G+M group. Our findings contrast with studies in adults showing durable benefits of metformin and insulin on HbA1c and β-cell responsiveness. Further investigation is needed to find effective treatments that prevent progression of dysglycemia in youth with IGT or recent-onset T2D. Disclosure T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. S. Edelstein: None. S.A. Arslanian: None. S. Caprio: None. P. Zeitler: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Research & Development, Merck & Co., Inc., Novo Nordisk Inc. T.A. Buchanan: Research Support; Self; Allergan, Apollo EndoSurgery. D.A. Ehrmann: None. K.J. Mather: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. E. Leschek: None. M. Tripputi: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S. K.J. Nadeau: None. R. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases