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 beta-cell function, including a 9-month follow-up after treatment withdrawal to test treatment effect durability. Objective Evaluate OGTT measures of glucose and beta-cell response through 12 months of intervention and 9 months of medication washout. Participants Youth (n = 91) aged 10 to 19 years with BMI >= 85th percentile and impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (T2D). Methods A multicenter 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 beta-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= .62; Met baseline 6.1 +/- 0.2 vs M12 6.0 +/- 0.2 mmol/L,P= .73) and 2-hour glucose (G -> Met baseline 10.2 +/- 0.4 vs M12 9.3 +/- 0.5 mmol/L,P= .03; Met baseline 10.2 +/- 0.4 vs M12 10.6 +/- 0.6 mmol/L,P= .88). Following medication withdrawal, fasting glucose worsened (G -> Met M21 8.6 +/- 1.8,P= .004; Met M21 7.8 +/- 0.7 mmol/L,P= .003), as did 2-hour glucose (G -> Met M21 13.2 +/- 1.4,P= .002; Met M21 13.1 +/- 1.2 mmol/L,P= .006), associated with declines in beta-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 beta-cell response worsened post-medication withdrawal, suggesting treatment must be long-term or alternative treatments pursued.