675-P: Effects of Liraglutide in T1D by Baseline Anthropometrics in ADJUNCT One and Two

Abstract

We re-evaluated the efficacy and safety of liraglutide, a GLP-1 analog, for use as adjunctive therapy in people with type 1 diabetes (T1D). Results from the two ADJUNCT trials suggested that residual beta-cell function is associated with more pronounced benefits and less risk of hypoglycemia. Here we analyze results of the two trials according to other baseline anthropometrics. ADJUNCT ONE (NCT01836523) and TWO (NCT02098395) were randomized controlled phase 3 trials in broad T1D populations (1398 and 835 participants, respectively) treated with liraglutide (1.8, 1.2 or 0.6 mg) or placebo. ADJUNCT ONE was a 52-week trial with a treat-to-target design and no limits on insulin titration; ADJUNCT TWO was a 26-week trial with an individual maximal insulin dose. In a post hoc analysis, we evaluated certain estimated placebo-adjusted treatment effects across clinically relevant participant subgroups. At week 26 in ADJUNCT ONE, placebo-adjusted reductions in HbA1c, body weight (BW) and daily insulin dose (up to -0.30 %-points, -5.0 kg and -12%, respectively, with liraglutide 1.8 mg) were significant (p<0.05) and greater than at week 52. In both trials, the placebo-adjusted reductions in HbA1c, BW and daily insulin dose with liraglutide did not depend (p>0.05) on baseline HbA1c or BMI at neither week 26 nor 52. The risk of clinically significant hypoglycemia (symptomatic episodes with blood glucose <3.1 mmol/L) or hyperglycemia with ketosis did not differ significantly (p>0.05 vs. placebo) by baseline HbA1c, BMI or insulin regimen. In ADJUNCT ONE and TWO, the efficacy and glycemic safety of liraglutide did not depend on key baseline anthropometrics. This leaves residual beta-cell function the only identified parameter impacting the treatment effect of the GLP-1 analog used as an adjunct to insulin in T1D. Together with recent progress in the understanding of T1D and of the benefits of GLP-1 receptor agonism, these findings suggest a role for GLP-1 receptor agonists in T1D, warranting further study. Disclosure T. F. Dejgaard: Advisory Panel; Self; Novo Nordisk, Consultant; Self; Boehringer Ingelheim International GmbH, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. L. Bardtrum: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. E. Christiansen: None. F. Kreiner: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. S. Madsbad: Advisory Panel; Self; AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp & Dohme; Novo Nordisk; Sanofi, Research Support; Self; Novo Nordisk, Boehringer Ingelheim, Speaker’s Bureau; Self; AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi. M. G. Von herrath: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. B. Von scholten: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. C. Mathieu: Advisory Panel; Self; Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma, Research Support; Self; Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics, Speaker’s Bureau; Self; Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis. Funding Novo Nordisk A/S