Diet, exercise, and weight loss can improve glycemic control, but most patients with type 2 diabetes eventually require glucose-lowering pharmacotherapy. An A1C goal of <7% (while minimizing hypoglycemia) is recommended for most patients to prevent or reduce the microvascular complications of diabetes (retinopathy, nephropathy, neuropathy). An A1C target of <8% may be appropriate for patients who are older, have comorbid conditions, or are at risk of serious hypoglycemia-associated adverse events.

Diet, exercise, and weight loss can improve glycemic control, but almost all patients with type 2 diabetes require antihyperglycemic drug therapy. Treating to a target A1C of <7% while minimizing hypoglycemia is recommended to prevent microvascular complications of diabetes (retinopathy, nephropathy, and neuropathy). An A1C target of <8% may be appropriate for some older patients.

Diet, exercise, and weight loss can improve glycemic control, but almost all patients with type 2 diabetes eventually require drug therapy. Treating to a glycated hemoglobin (A1C) concentration of <7% can prevent microvascular complications (retinopathy, nephropathy, and neuropathy), but whether it prevents macrovascular complications and death is unclear. An A1C target of <8% may be appropriate for older patients and those with underlying cardiovascular disease (CVD), a history of severe hypoglycemia, diabetes-related complications, a limited life expectancy, or a long duration of disease.

For many years, the goal of drug therapy for most patients with type 2 diabetes has been to achieve and maintain an A1C of <7%. Achieving that goal can prevent microvascular complications (diabetic retinopathy, nephropathy, neuropathy), but whether it prevents macrovascular complications (myocardial infarction [MI], stroke) has been less clear. The FDA now requires that cardiovascular safety studies be performed for all new drugs for type 2 diabetes.1 Recent findings that some of the newer second-line drugs for type 2 diabetes have cardiovascular benefits have led to new interest in the cardiovascular efficacy and safety of all antidiabetic drugs.

The goal of drug therapy for type 2 diabetes is to achieve and maintain a near-normal glycated hemoglobin (A1C) concentration without inducing hypoglycemia; the target is generally an A1C of ≤7%. Treating to this target has been shown to prevent microvascular complications (retinopathy, nephropathy, and neuropathy), but whether it prevents macrovascular outcomes is unclear. An A1C target of <8% may be appropriate for older patients and those with underlying cardiovascular disease, a history of severe hypoglycemia, diabetes-related complications or comorbidities, or a long duration of disease.

The FDA has approved Jentadueto XR (Boehringer Ingelheim/Lilly), a once-daily extended-release formulation of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin and the biguanide metformin, for oral treatment of type 2 diabetes. Linagliptin and metformin have been available for years in a twice-daily immediate-release combination (Jentadueto). Once-daily extended-release formulations combining metformin with the DPP-4 inhibitors saxagliptin (Kombiglyze XR) and sitagliptin (Janumet XR) are also available.

The FDA has approved Glyxambi (Boehringer Ingelheim/Lilly), a fixed-dose combination of empagliflozin (Jardiance) and linagliptin (Tradjenta), for oral treatment of type 2 diabetes in adults. It is the first combination of a sodium-glucose co-transporter 2 (SGLT2) inhibitor and a dipeptidyl peptidase-4 (DPP-4) inhibitor to be approved in the US.

The goal of drug therapy for type 2 diabetes is to achieve and maintain a near-normal A1C concentration without inducing hypoglycemia; the target is generally an A1C of <7.0%. Treating to this target has been shown to prevent the microvascular complications of retinopathy and nephropathy, but whether it prevents macrovascular outcomes remains unclear. Three large trials found that intensive glucose control did not reduce the incidence of macrovascular events. One of these trials (ACCORD) in >10,000 patients with type 2 diabetes, with or at high-risk for cardiovascular disease, found that treating patients intensively with antihyperglycemic drugs to an A1C target of 6.0% for a mean of 3.7 years did not significantly reduce the incidence of major cardiovascular events (the primary endpoint) and was associated with increased all-cause mortality compared to patients treated to an A1C target of 7.0-7.9%. An A1C target of 7-8% may be prudent in older patients and in those with underlying cardiovascular disease, severe hypoglycemia, or multiple diabetes-related complications or co-morbidities.

The FDA has approved the dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin (Nesina – Takeda) for treatment of type 2 diabetes. In addition to the single-ingredient product, the FDA also approved fixed-dose combinations of alogliptin/metformin (Kazano) and alogliptin/pioglitazone (Oseni) for the same indication. Alogliptin is the fourth DPP-4 inhibitor to become available in the US. The other three – saxagliptin (Onglyza), sitagliptin (Januvia), and linagliptin (Tradjenta) – are also available in fixed-dose combinations with metformin.

Canagliflozin (kan" a gli floe' zin; Invokana – Janssen), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has been approved by the FDA for oral treatment of type 2 diabetes.