Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial

Abstract

OBJECTIVE To investigate whether liraglutide added to treat-to-target insulin improves glycemic control and reduces insulin requirements and body weight in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 52-week, double-blind, treat-to-target trial involving 1,398 adults randomized 3:1 to receive once-daily subcutaneous injections of liraglutide (1.8, 1.2, or 0.6 mg) or placebo added to insulin. RESULTS HbA_1c level was reduced 0.34–0.54% (3.7–5.9 mmol/mol) from a mean baseline of 8.2% (66 mmol/mol), and significantly more for liraglutide 1.8 and 1.2 mg compared with placebo (estimated treatment differences [ETDs]: 1.8 mg liraglutide −0.20% [95% CI −0.32; −0.07]; 1.2 mg liraglutide −0.15% [95% CI −0.27; −0.03]; 0.6 mg liraglutide −0.09% [95% CI −0.21; 0.03]). Insulin doses were reduced by the addition of liraglutide 1.8 and 1.2 mg versus placebo (estimated treatment ratios: 1.8 mg liraglutide 0.92 [95% CI 0.88; 0.96]; 1.2 mg liraglutide 0.95 [95% CI 0.91; 0.99]; 0.6 mg liraglutide 1.00 [95% CI 0.96; 1.04]). Mean body weight was significantly reduced in all liraglutide groups compared with placebo ETDs (1.8 mg liraglutide −4.9 kg [95% CI −5.7; −4.2]; 1.2 mg liraglutide −3.6 kg [95% CI −4.3; −2.8]; 0.6 mg liraglutide −2.2 kg [95% CI −2.9; −1.5]). The rate of symptomatic hypoglycemia increased in all liraglutide groups (estimated rate ratios: 1.8 mg liraglutide 1.31 [95% CI 1.07; 1.59]; 1.2 mg liraglutide 1.27 [95% CI 1.03; 1.55]; 0.6 mg liraglutide 1.17 [95% CI 0.97; 1.43]), and hyperglycemia with ketosis increased significantly for liraglutide 1.8 mg only (event rate ratio 2.22 [95% CI 1.13; 4.34]). CONCLUSIONS Liraglutide added to insulin therapy reduced HbA_1c levels, total insulin dose, and body weight in a population that was generally representative of subjects with type 1 diabetes, accompanied by increased rates of symptomatic hypoglycemia and hyperglycemia with ketosis, thereby limiting clinical use in this group.