The FDA has approved fixed-dose combinations of metformin with either canagliflozin (Invokamet) or dapagliflozin (Xigduo XR) for treatment of patients with type 2 diabetes not adequately controlled with any one of these drugs, or in those already being treated with both metformin and either canagliflozin or dapagliflozin.

The FDA has warned that use of an SGLT2 (sodium-glucose co-transporter 2) inhibitor for treatment of type 2 diabetes may lead to ketoacidosis.1 Three SGLT2 inhibitors, canagliflozin (Invokana, Invokamet), dapagliflozin (Farxiga, Xigduo XR), and empagliflozin (Jardiance, Glyxambi), are approved for treatment of type 2 diabetes in the US. Between March 2013 and June 2014, 20 cases of ketoacidosis requiring emergency room visits or hospitalization were reported in patients who had recently started taking an SGLT2 inhibitor; the median time to onset of symptoms after initiation of therapy was 2...

The FDA has approved Synjardy (Boehringer Ingelheim/Lilly), a fixed-dose combination of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) and metformin (Glucophage, and others), for treatment of patients with type 2 diabetes not adequately controlled on either of these drugs alone or already being treated with both empagliflozin and metformin. It is the third SGLT2 inhibitor/metformin combination to be approved in the US.

The FDA has approved Qtern (AstraZeneca), a fixed-dose combination of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin (Farxiga) and the dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin (Onglyza), for oral treatment of adults with type 2 diabetes. Dapagliflozin and saxagliptin have each been available for years alone and in combination with extended-release metformin (Xigduo XR; Kombiglyze XR). Three SGLT2/DPP-4 inhibitor combinations are now available in the US (see Table 2).

View the Comparison Chart: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors

The FDA has approved the sodium-glucose co-transporter 2 (SGLT2) inhibitor ertugliflozin (Merck) for treatment of adults with type 2 diabetes, both alone (Steglatro) and in fixed-dose combinations with metformin (Segluromet) and sitagliptin (Steglujan). Ertugliflozin is the fourth SGLT2 inhibitor to be approved in the US. All four are available in combination with metformin and three are available in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor (see Table 3).

At the same time that the FDA announced it was strengthening existing warnings about the risk of acute kidney injury in patients with type 2 diabetes treated with the sodium-glucose co-transporter 2 (SGLT2) inhibitors canagliflozin (Invokana, and others) and dapagliflozin (Farxiga, and others), a study was published showing that the third SGLT2 inhibitor, empagliflozin (Jardiance, and others), slowed the progression of renal dysfunction in patients with type 2 diabetes.

Since 2008, because of safety concerns, the FDA has mandated that long-term cardiovascular outcomes trials be conducted for all new drugs for type 2 diabetes. Reductions in the incidence of macrovascular complications in these trials with some sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients at risk for cardiovascular disease (see Table 1) have led to new recommendations.

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.