Metformin is typically the first line of drug therapy for patients with T2DM. However, the choice of therapeutic agents after metformin becomes more complicated for older patients, and current treatment recommendations do not explicitly discuss this difficulty. Older patients with T2DM are a very heterogeneous group with multiple comorbidities, increased risk of hypoglycemia, and greater susceptibility to adverse effects of antihyperglycemic drugs, making their treatment particularly challenging. Ideally, preferred drugs in older patients should not be cleared by the kidneys and should have a low risk of adverse cardiovascular effects or hypoglycemia. Generally, metformin, incretin-based therapies (ie, glucagon-like pepetide-1 [GLP-1] agonists and dipeptidyl peptidase-4 [DPP-4] inhibitors), and long-acting insulin should be preferred over other treatment options (sulfonylureas, glinides, and glitazones).