Withdrawal of Medications Leads to Worsening of OGTT Parameters in Youth with Impaired Glucose Tolerance or Recently-Diagnosed Type 2 Diabetes.

BACKGROUND The RISE Pediatric Medication Study compared strategies for preserving β-cell function, including a 9-month follow-up after treatment withdrawal to test treatment effect durability. OBJECTIVE Evaluate OGTT measures of glucose and β-cell response through 12 months of intervention and 9 months of medication washout. PARTICIPANTS Youth (n=91) aged 10-19 years with BMI ≥85th percentile and impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (T2D). METHODS A multi-center randomized clinical trial comparing insulin glargine for 3 months followed by metformin for 9 months (G→Met) or metformin alone (Met) for 12 months. We report within-group changes from baseline to end of medication intervention (M12), baseline to 9 months post-medication withdrawal (M21), and end of medication (M12) to M21. OGTT C-peptide index [CPI] paired with 1/fasting insulin evaluated β-cell response. RESULTS At M12, both treatments were associated with stable fasting glucose (G→Met baseline 6.0±0.1 vs. M12 5.9±0.2 mmol/L, p=0.62; Met baseline 6.1±0.2 vs. M12 6.0±0.2 mmol/L, p=0.73) and 2-hour glucose (G→Met baseline 10.2±0.4 vs. M12 9.3±0.5 mmol/L, p=0.03; Met baseline 10.2±0.4 vs. M12 10.6±0.6 mmol/L, p=0.88). Following medication withdrawal, fasting glucose worsened (G→Met M21 8.6±1.8, p=0.004; Met M21 7.8±0.7 mmol/L, p=0.003), as did 2-hour glucose (G→Met M21 13.2±1.4, p=0.002; Met M21 13.1±1.2 mmol/L, p=0.006), associated with declines in β-cell response. CONCLUSIONS G→Met and Met were associated with stable glucose measures during 12 months of treatment in youth with IGT or recently diagnosed T2D. Glucose and β-cell response worsened post-medication withdrawal, suggesting treatment must be long-term or alternative treatments pursued. This article is protected by copyright. All rights reserved.