Practical limitations of complex insulin therapies in type 2 diabetes: Focus on therapy simplification using fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist.

Until recently, people with type 2 diabetes mellitus (PwT2DM) with poor glycaemic control on oral antidiabetic medication were initiated on insulin therapy. While insulin-based therapies have been efficient in reducing hyperglycaemia, they have also been linked with an increased risk of hypoglycaemia, increased treatment burden, and weight gain. The advent of novel classes of antidiabetic agents, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) presents a significant shift in the T2DM treatment algorithms. These medications are not only efficient in the reduction of glycaemia but are also able to reduce weight and have cardiovascular and renal benefits. PwT2DM on complex insulin regimens can now benefit from therapy simplification, taking advantage of once-daily fixed-ratio combinations (FRC) of basal insulin and glucagon-like peptide-1 receptor agonist. Current evidence suggests that this approach is equally efficient in terms of glycaemic control with the additional benefit of the reduction of body weight, total daily dose of insulin, and the number of insulin injections administered per day with no increase or reduction of hypoglycaemia. The primary aim of this review is to present the current evidence supporting the simplification of complex insulin regimens in PwT2DM with the two currently available FRCs on the market (insulin glargine 100 U/mL and GLP-1 RA lixisenatide [iGlarLixi] or insulin degludec and GLP-1 RA liraglutide [IDegLira]) and to provide a simple clinical practice-oriented algorithm for clinicians based on the currently available evidence.