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 lixisenatide (Sanofi), a short-acting injectable GLP-1 (glucagon-like peptide-1) receptor agonist, for once-daily treatment of adults with type 2 diabetes, both alone (Adlyxin) and in a fixed-ratio combination with insulin glargine (Soliqua 100/33). Lixisenatide has been available since 2013 in many other countries as Lyxumia. It is the fifth GLP-1 receptor agonist to be approved in the US.

The goal of drug therapy for type 2 diabetes is to achieve and maintain a near-normal glycated hemoglobin (A1C) concentration without inducing hypoglycemia; for most patients, the target A1C is <7%. Metformin is the preferred first-line treatment, but most patients with type 2 diabetes eventually require multidrug therapy and/or insulin to achieve glycemic control.

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).

Nateglinide (Starlix), a new meglitinide oral glucose-lowering agent, has been approved by the FDA.

The FDA has approved tirzepatide (Mounjaro – Lilly), a peptide hormone with activity at both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, to improve glycemic control in adults with type 2 diabetes. Tirzepatide, which is injected subcutaneously once weekly, is the first dual GIP/GLP-1 receptor agonist to become available in the US. Selective GIP receptor agonists are not available in the US; GLP-1 receptor agonists have been available for years.

The FDA has approved a new tablet formulation of bromocriptine mesylate (Cycloset – VeroScience) for treatment of type 2 diabetes in adults. Bromocriptine (Parlodel, and others) is an ergot-derived dopamine agonist that has been used for more than 20 years to treat hyperprolactinemia, acromegaly, Parkinson’s disease and restless leg syndrome.

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.

Dapagliflozin (dap" a gli fl oe' zin; Farxiga – Bristol-Myers Squibb/AstraZeneca), an SGLT2 (sodium-glucose co-transporter 2) inhibitor, has been approved by the FDA for oral treatment of type 2 diabetes. Dapagliflozin is the second SGLT2 inhibitor to be approved for this indication; canagliflozin (Invokana) was the first .

Sitagliptin phosphate (Januvia - Merck) is the first dipeptidyl-peptidase-4 (DPP-4) inhibitor to be marketed for treatment of type 2 diabetes. It has been approved by the FDA for oral use as monotherapy or in combination with metformin (Glucophage, and others), pioglitazone (Actos) or rosiglitazone (Avandia).