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_1c) 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_1c 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.