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

Abstract

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, I2=0%). Significant weight reduction, up to 4.87 kg with liraglutide 1.8 mg was also observed (95% CI -5.31 to -4.43, I2=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, I2=0%), while it increased significantly the odds for gastrointestinal adverse events (for nausea, OR=4.70, 95% CI 3.68-6.00, I2=37%, and for vomiting, OR=2.50, 95% CI 1.54-4.72, I2=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.

The impact of pharmacological and lifestyle interventions on body weight in people with type 1 diabetes: A systematic review and meta‐analysis

“…After screening the articles, 33 of them met the inclusion criteria. Of these, 18 were already part of seven previously published systematic reviews, 30–36 with a focus on both glycaemic outcomes (but not weight) and the safety and efficacy of pharmacological interventions; however, these were still included in the review (Table S5). The full text versions of all 33 articles were obtained, which included data pertaining to 9344 participants.…”

Side Effects Associated with Liraglutide Treatment for Obesity as Well as Diabetes

“…A recent study found no reported cases of pancreatic or thyroid cancer within a year in patients with T1DM taking insulin treated with liraglutide (0.6-1.8 mg) or placebo. 19 Another study observed no increase in cancer with the use of GLP-1 receptor agonists (including 0.9-3.0 mg of liraglutide) in patients with T2DM. 40 In a previous study of patients with T2DM, use of liraglutide (0.1-1.8 mg) increased the risk of cancer by 35%, but was not statistically significant.…”

“…Individual patient-level data meta-analysis of the Liraglutide Effect and Action in Diabetes program suggested that treatment with 1.8 mg of liraglutide significantly reduced alanine aminotransferase 19,22,24,25 Co-administered antidiabetic drugs should be adjusted according to glucose monitoring results and hypoglycemic risk. 1 in patients with T2DM and abnormal baseline alanine aminotransferase and showed a trend towards improving hepatic steatosis.…”

Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations on the use of sodium–glucose cotransporter inhibitors with insulin for treatment of type 1 diabetes (Updated October 2020)

“…GLP‐1 analogues and receptor agonists may be helpful in subgroups of people with type 1 diabetes but the reductions in HbA 1c are modest [MD −3 mmol/mol (−0.24%) with liraglutide 1.8 mg] although weight reductions were significant (4.87 kg with liraglutide 1.8 mg), insulin dose reduced, hypoglycaemia reduced but not significantly (OR 0.80) and GI adverse events increased significantly (OR nausea 4.70, vomiting 2.50) 25,26 . DPP4 inhibitors added to insulin did result in a small but insignificant reduction in HbA 1c [1 mmol/mol (0.07%)] and no consistent effect on glucose variability in people with type 1 diabetes 27 .…”