The Restoring Insulin Secretion (RISE) Study examined the effect of medications to preserve β-cell function in 267 adults with IGT or drug-naïve, recently diagnosed T2D. Participants were randomized to receive 12 months of blinded metformin (MET) or placebo, 12 months of liraglutide (LIRA)+MET, or 3 months of glargine followed by 9 months of MET, all followed by 9 months off treatment. We examined glycemic worsening, defined as progression from IGT to diabetes by fasting or 2-h glucose on an OGTT at baseline, 6, 12, 15 and 21 months or a rise in quarterly HbA1c to ≥7%s. Time-to-worsening was evaluated across treatment groups using a modified product-limit life-table distribution with a log-rank test. Compared to the other treatments, LIRA+MET had less glycemic worsening at 12 months (on treatment) and 21 months (9 months off treatment); each p<0.01. After stopping treatment, group differences persisted but all groups showed similar rates of glycemic progression (Figure). Using logistic regression, independent predictors of worsening glycemia by months 12 and 21 were treatment with LIRA+MET (p=0.01; p=0.03) and baseline 2-h glucose (p=0.02; p=0.03). Overall, despite similar rates of glycemic worsening after discontinuation of therapy, the sustained on-treatment interval of normoglycemia resulted in less glycemic worsening in LIRA+MET compared with the other RISE interventions.


S. Sam: None. S. Edelstein: None. K. Utzschneider: Other Relationship; Self; Medtronic. T.S. Hannon: None. E. Barengolts: None. A. Xiang: None. D.A. Ehrmann: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None.


American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

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