The Clinical Use of a Fixed-Dose Combination of Insulin Degludec and Liraglutide (Xultophy 100/3.6) for the Treatment of Type 2 Diabetes

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the fixed-dose combination of insulin degludec and the glucagon-like peptide-I receptor agonist (GLP-1 RA), liraglutide (IDegLira) in the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A PubMed and MEDLINE search (1966 to July 2017) of the keywords insulin degludec, liraglutide, and type 2 diabetes mellitus was conducted. References were reviewed to identify additional citations. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacokinetics, pharmacology, clinical efficacy, or safety of IDegLira in humans. Data Synthesis: IDegLira displayed pharmacokinetic and pharmacodynamic properties similar to that of the individual components. IDegLira has shown significant hemoglobin A1C (A1C) reductions of 1.3% to 1.9% and fasting plasma glucose reductions of 45 to 65 mg/dL when used in patients with T2DM previously receiving oral antihyperglycemic agents (AHAs), GLP-1 RAs, or basal insulin. Weight loss also occurred when IDegLira was started in patients previously receiving oral AHAs or basal insulin. Adverse effects (AEs) tended to be mild and transient. The most common AEs were headache, nasopharyngitis, upper-respiratory infections, and gastrointestinal disorders. Hypoglycemia risk was lower with IDegLira than basal insulin alone but higher than liraglutide alone. Conclusions: IDegLira may provide additional glycemic control with fewer AEs for patients uncontrolled on a GLP-RA or basal insulin alone. Additional studies evaluating use in patients on oral AHAs with higher A1C values and in comparison to bolus insulin are needed.