Optimizing Fixed-Ratio Combination Therapy in Type 2 Diabetes

The progressive nature of type 2 diabetes (T2D) means that many patients will require basal insulin therapy at some point in the course of the disease due to β-cell failure. As basal insulin primarily targets fasting plasma glucose, patients may still experience considerable postprandial glucose excursions and therefore require an additional agent to achieve good glycemic control. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide an alternative to prandial insulin, with the benefits of fewer daily injections, and a lower risk of hypoglycemia and weight gain. Two fixed-ratio combinations (FRCs) of basal insulin and a GLP-1 RA are now available in the USA and the EU: insulin glargine + lixisenatide (iGlarLixi) and insulin degludec + liraglutide (IDegLira). Titratable FRCs are suitable for most patients with T2D and can help to simplify treatment regimens into one daily injection, potentially aiding in patient adherence. The complementary modes of action of the two components target seven of the many known pathophysiologic defects in T2D. FRCs have demonstrated enhanced glycemic control compared with their constituent components alone, comparable risk of hypoglycemia compared with basal insulin alone, and better tolerability compared with the GLP-1RA component alone due to the slower titration. In this article, we discuss the advantages of FRCs over multiple daily injections, present case studies of typical patients who could benefit from FRC therapy, and outline practical considerations for the initiation of FRC therapy in clinical practice.