The RISE Consortium conducted a study in adults with IGT or recently diagnosed T2D to determine if β-cell function can be conserved or improved. Participants were randomized to GB, metformin, liraglutide + metformin (L+M), or placebo. β-cell function was assessed at baseline (BAS) and at 12 mo (12M) on therapy. Hyperglycemic clamp measures of β-cell function were: acute C-peptide (CP) response to glucose (ACPRg), steady-state CP (SSCP) at a plasma glucose of 11.1 mmol/L and maximal CP response to arginine, a non-glucose secretogogue, at a plasma glucose >25 mmol/L (ACPRmax). At BAS, BMI, ACPRg, SSCP, and ACPRmax were similar across groups. BMI was lower at 12M in all treatment groups and unchanged in those on placebo (Table). Analyses were adjusted for age, sex, and race. Participants randomized to L+M had significant increases in ACPRg and SSCP. There was also a modest but significant attenuation in ACPRmax in the L+M group. In contrast, participants who received GB or metformin alone had no change in β-cell function. Liraglutide appears to result in increased acute and steady-state responses, but greater β-cell “exhaustion” evidenced by a relative reduction in the CP response to arginine. Mechanisms responsible for this finding and its long-term implications are needed.


D.A. Ehrmann: None. S. Edelstein: None. A. Xiang: None. T.A. Buchanan: None. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. S. Caprio: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. K.J. Nadeau: None. 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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