Liraglutide as Adjunct to Insulin Treatment in Patients with Type 1 Diabetes: A Systematic Review and Meta-analysis

Background: A few Randomized Controlled Trials (RCTs) have evaluated the use of liraglutide in Type 1 Diabetes (T1D). Through the present systematic review and meta-analysis, we aim at critically appraising and summarizing those RCTs, providing precise effect estimates. Methods: We searched major databases and grey literature from their inception to October 2018, for RCTs with a duration >= 12 weeks, comparing liraglutide with placebo or any other comparator as adjunct to insulin in patients with T1D, investigating major efficacy and safety endpoints. This review is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Results: We included 5 trials with 2,445 randomized participants. Liraglutide provided modest reductions in HbA1c, with liraglutide 1.8 mg producing the greatest decrease (MD = -0.24%, 95% CI -0.32 to -0.16, I-2=0%). Significant weight reduction, up to 4.87 kg with liraglutide 1.8 mg was also observed (95% CI -5.31 to -4.43, I-2=0%). Decrease in total daily insulin dose, primarily driven by a decrease in bolus insulin requirements, was demonstrated. Liraglutide decreased non-significantly the odds for severe hypoglycemia (OR=0.80, 95% CI 0.57-1.14, I-2=0%), while it increased significantly the odds for gastrointestinal adverse events ( for nausea, OR=4.70, 95% CI 3.68-6.00, I-2=37%, and for vomiting, OR= 2.50, 95% CI 1.54-4.72, I-2=27%). A significant increase in heart rate was also demonstrated. No association with diabetic ketoacidosis or malignancies was identified. Conclusion: In patients with T1D, liraglutide might prove be an adjunct to insulin, improving glycemic control, inducing body weight loss and decreasing exogenous insulin requirements and severe hypoglycemia.