Chantal Mathieu1, Bernard Zinman2, Joanna Uddén Hemmingsson3, Vincent Woo4, Peter Colman5, Erik Christiansen6, Martin Linder6, Bruce Bode7. 1. Gasthuisberg Hospital, University of Leuven, Leuven, Belgium chantal.mathieu@med.kuleuven.be. 2. Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. 3. Capio St. Görans Hospital and the Karolinska Institute, Stockholm, Sweden. 4. Health Sciences Centre, Winnipeg, Manitoba, Canada. 5. Royal Melbourne Hospital, Parkville, Victoria, Australia. 6. Novo Nordisk A/S, Bagsværd, Denmark. 7. Atlanta Diabetes Associates, Atlanta, GA.
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:HbA1c 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 HbA1c 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.
RCT Entities:
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: HbA1c 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 HbA1c 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.
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