Co-Formulations as the First Injectable in Type 2 Diabetes: A Review of Efficacy, Safety, and Implications in Clinical Practice

Background: Progression of type 2 diabetes will necessitate the use of injectable therapies in a significant number of people. Co-formulations of degludec with liraglutide (IDegLira) and glargine with lixisenatide (IGlarLixi) are currently recommended for intensification in people with type 2 diabetes on basal insulin or glucagon-like peptide receptor agonist (GLP-1RA) alone or in people with type 2 diabetes who are naïve to insulin with very high glycated haemoglobin. Co-formulation of aspart with degludec (IDegAsp) is recommended as a substitute for premixed insulin. The aim of this article is to review the evidence in the use of co-formulations as the first injectable in type 2 diabetes and its clinical implications. Summary: In people with type 2 diabetes who are naïve to insulin or GLP-1RA, IDegLira and IGlarLixi achieved stable and durable glycaemic control over a wide range of baseline glycated haemoglobin (HbA1c) levels. People on IDegLira and IGlarLixi had lesser risk of hypoglycaemia and weight gain in studies compared to basal insulin and lesser gastrointestinal adverse effects in comparison to GLP-1RA. IDegAsp achieved similar glycaemic control to basal and premixed insulin with lesser risk of nocturnal hypoglycaemia. Key Messages: IDegLira, IGlarLixi, and IDegAsp can be used as the first injectable in people with type 2 diabetes with very high glycated haemoglobin on oral antidiabetic drugs. These co-formulations combine efficacy and durability with lesser injection burden. The components of these agents have proven cardiovascular and renal safety. Their limitations in flexibility of dosing, renal and cardiovascular considerations, and adverse effects are discussed.