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:

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.

• Authors: Chantal Mathieu, Bernard Zinman, Joanna Uddén Hemmingsson, Vincent Woo, Peter Colman, Erik Christiansen, Martin Linder, Bruce Bode, ADJUNCT ONE Investigators
• Journal: Diabetes care (Diabetes Care) Vol. 39 Issue 10 Pg. 1702-10 (Oct 2016) ISSN: 1935-5548 [Electronic] United States
• PMID: 27506222 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2016 by the American Diabetes Association.

Chemical References

• Glycated Hemoglobin A
• Hypoglycemic Agents
• Insulin
• Liraglutide

Topics

• Adult
• Diabetes Mellitus, Type 1 (blood, drug therapy)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glycated Hemoglobin (analysis)
• Humans
• Hypoglycemic Agents (administration & dosage)
• Injections, Subcutaneous
• Insulin (administration & dosage)
• Liraglutide (administration & dosage)
• Male
• Middle Aged
• Treatment Outcome