Initial combination with linagliptin and metformin in newly diagnosed type 2 diabetes and severe hyperglycemia.

Making appropriate treatment decisions for patients newly diagnosed with type 2 diabetes mellitus (T2DM) and severe hyperglycemia (glycated hemoglobin [HbA1c]>10% or fasting plasma glucose≥250 mg/dL) presents a formidable challenge to primary care physicians. Extreme defects in insulin secretion make it unlikely that these patients will achieve glycemic targets with metformin monotherapy. Additionally, uncontrolled hyperglycemia is associated with an increased risk of short-term acute complications, such as hyperosmolar coma, and long-term complications affecting the micro- and macrovasculature. Thus, severely hyperglycemic patients require prompt, intensive treatment to re-establish glycemic control. Current guidelines indicate that either initial insulin therapy or initial combination therapy with metformin plus non-insulin drug(s) are the treatments of choice for these challenging-to-treat patients. This mini-review examines the clinical evidence supporting these two treatment options, with particular reference to the findings of a phase 3 study of treatment with an initial combination of metformin plus the dipeptidyl peptidase-4 inhibitor, linagliptin. Intensive insulin therapy can induce sustained euglycemia and improve beta-cell function in newly diagnosed patients. However, insulin use is associated with an increased risk of adverse events, such as hypoglycemia and weight gain. These potentially serious side effects cause concern among patients and physicians, and are a major barrier to initiating and maintaining adherence to insulin treatment. In the phase 3 study, open-label treatment of severely hyperglycemic patients (HbA1c≥11.0%) with linagliptin plus metformin resulted in a mean change in HbA1c of -3.7%±1.7%. This combination therapy was generally well tolerated with most adverse events being of mild or moderate intensity; asymptomatic hypoglycemia was reported by just 1 of 66 (1.5%) patients. These findings provide evidence in support of linagliptin plus metformin as a well-tolerated and effective treatment alternative to insulin for new-onset patients with T2DM and severe hyperglycemia.