Combination Glucose-Lowering Therapy Plans in T2DM: Case-Based Considerations

Type 2 diabetes mellitus (T2DM) is a complex disease, and while lifestyle interventions remain the cornerstone of therapy, most patients will also require pharmacotherapy. Current diabetes treatment guidelines and algorithms recommend an individualized approach to setting glycemic goals and selecting treatment. Although a single antihyperglycemic agent may be appropriate as the initial T2DM pharmacotherapy, the progressive nature of the disease due to declining pancreatic β-cell function will result in the vast majority of T2DM patients eventually requiring two or more antihyperglycemic agents. The American Association of Clinical Endocrinologists/American College of Clinical Endocrinology T2DM management algorithm recommends initial dual agent combination therapy when a single agent is unlikely to achieve their target glycemia, i.e., for those patients with an HbA1c ≥ 7.5 and an individualized HbA1c target of < 7.5%. The American Diabetes Association Standards of Care recommend combination pharmacotherapy for those patients presenting with very elevated HbA1c levels (e.g., ≥ 9% and < 10%). Metformin (if well tolerated and not contraindicated) is the initial pharmacologic choice for most patients; selection of another antihyperglycemic agent to the regimen will depend on the presence of atherosclerotic cardiovascular disease and other patient-specific factors (e.g., age, known duration of T2DM, history of or risk for hypoglycemia and/or adverse consequences from hypoglycemia, other comorbidities, and available resources), along with drug-specific factors (e.g., risk for hypoglycemia, potential effects on weight, drug adverse event profiles, and cost). Combination therapy may be administered as a multi-pill regimen, a single-pill combination (i.e., fixed-dose combination oral therapy), or as a combination of oral and/or injectable therapies. This paper provides two illustrative case presentations to demonstrate how current treatment recommendations and algorithms can be used to guide the selection of non-insulin-based combination therapy for patients with T2DM in primary care settings and discusses the relative merits of several possible approaches for each patient.