COMBINE 2 is better than one: shaping the future of therapeutics in inadequately controlled type 2 diabetes.

During treatment intensification of injectable therapies among persons with type 2 diabetes mellitus (T2DM) without evidence of severe insulin deficiency, a glucagon-like peptide-1 agonist (GLP-1 RA) is preferred to insulin. However, due to its progressive nature, many individuals over the course of disease will ultimately require insulin treatment. The use of fixed-ratio combination of basal insulin and GLP-1 RA represents a practical and convenient method for treatment intensification. It has been shown to be more efficacious in improving glycemic control, compared with GLP-1 RA or basal insulin alone, and similarly effective with lower insulin dose in reducing glycated hemoglobin (HbA) levels, along with less weight gain, and a lower risk of hypoglycemia compared with basal/bolus insulin therapy. The recently published COMBINE 2 trial reported that switching to weekly combination therapy of basal insulin icodec and semaglutide (IcoSema), compared with semaglutide, results in greater HbA reduction, similar risk of clinically significant or severe hypoglycemia and comparable gastrointestinal tolerability, but unfavorable weight change among individuals with T2DM inadequately controlled with GLP-1 RA therapy, with or without additional oral glucose-lowering drugs. IcoSema represents an effective, safe, and convenient therapeutic choice for treatment intensification in individuals with T2DM inadequately controlled with GLP-1 RA therapy.