Increased priority for regimens involving incretin-based and insulin therapy.

The ADA/EASD and AACE guidelines emphasize the importance of individualizing treatment to best meet each patient's situation. Metformin remains the preferred choice as initial therapy for most patients. The 2009 AACE algorithm elevated the role of incretin-based therapies (GLP-1R agonists and DPP-4 inhibitors) relative to previous algorithms and this has been endorsed by subsequent algorithms and guidelines. The incretin-based therapies and insulin therapy should be considered with very high priority. Either incretin-based therapy or insulin therapy can be used as monotherapy or in combination with other agents. The GLP-1R agonists are especially useful when attempting to reduce the risk of hypoglycemia and when assisting the patient to achieve weight loss. Insulin therapy is especially useful when the HbA1c level is >9.0% or when symptoms of glucotoxicity are present. Insulin is the recommended treatment when other agents fail to achieve the desired target levels for HbA1c, FPG, and PPG. The combination of a GLP-1R agonist with basal insulin can provide better glycemic control than either agent alone, with less weight gain and glycemic outcomes for combined therapy with a long-acting basal insulin analog and a glucagon-like peptide-1 receptor agonist a markedly lower incidence of hypoglycemia than with use of basal insulin alone.