Therapies that preserve β-cell function and enhance glycemic control in type 2 diabetes are of great value. We examined β-cell function in GRADE participants after one year of intervention with insulin glargine U-100, glimepiride, liraglutide or sitagliptin. Participants who remained on originally assigned medication and had complete OGTT data at baseline and Year 1 were analyzed (n=3342 of 5047 initially randomized) . OGTT derived β-cell responses were measured as the ratio of the increment of C-peptide to glucose in the first 30 minutes (CPI) and over 120 minutes (CP/G AUC) . At baseline, age (57.7±9.7 y) , sex (63.5% male) , race (66.8% White) , BMI (34.2±6.7 kg/m2) , fasting C-peptide (1.3±0.5 nmol/L) , HOMA-B (87±35.2 %) , CPI (0.08±0.nmol/mg) and CP/G AUC (1.1±0.6 nmol/mg) did not differ by treatment group. At Year 1, measures of β-cell function were different by treatment groups (Table) . After pairwise analysis, glargine had the lowest fasting C-peptide while CP/G AUC was highest in the liraglutide group. When tested for treatment heterogeneity across subgroups, participants with longer duration of diabetes had smaller increases in CPI and CP/G AUC. Decreased fasting C-peptide by glargine is likely due to lower endogenous insulin secretion in the setting of exogenous insulin. Improved β-cell responses with liraglutide may indicate better β-cell function during the first year of treatment.


N. Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi. Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. J. Albu: None. R.M. Cohen: Research Support; Dexcom, Inc. R.A. DeFronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk. Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc. Speaker’s Bureau; AstraZeneca. E. Diaz: None. A. Ghosh: None. J.A. Luchsinger: None. J.B. McGill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals. Consultant; Bayer AG, Boehringer Ingelheim International GmbH. Research Support; Dexcom, Inc., Novo Nordisk. L. Sayyed Kassem: None. W.V. Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. K. Utzschneider: Consultant; Nevro Corp. N. Younes: None. S.E. Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc.


National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246, U34-DK-088043)

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