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.

The FDA has approved Trijardy XR (Boehringer Ingelheim/Lilly), a fixed-dose combination of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin, and extended-release metformin, for oral treatment of type 2 diabetes in adults. Empagliflozin and linagliptin have been available in a fixed-dose combination as Glyxambi since 2015, and both have been available in 2-drug combinations with extended-release metformin for years (see Table 1).

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.

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 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.

Linagliptin (Tradjenta) and metformin (Glucophage, and others) are now available as a fixed-dose combination (Jentadueto – Boehringer Ingelheim/Lilly) for oral treatment of type 2 diabetes in adults. Metformin is generally the preferred first-line agent for treatment of type 2 diabetes, but most patients eventually require treatment with multiple drugs. Linagliptin is a dipeptidyl peptidase-4 (DDP-4) inhibitor like sitagliptin (Januvia) and saxagliptin (Onglyza). Both sitagliptin and saxagliptin are also available in fixed-dose combinations with metformin.