The American College of Physicians (ACP) recommends that clinicians prescribe metformin to patients with type 2 diabetes when pharmacologic treatment is required to improve glycemic control, according to the guideline update published in the Annals of Internal Medicine.
In addition, the ACP recommends that clinicians consider adding a sulfonylurea, a thiazolidinedione, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, or a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin if a second oral therapy is needed.
The ACP created the guideline to update the 2012 ACP guidelines that provide clinical recommendations on oral pharmacologic treatment of type 2 diabetes in adults. Researchers conducted a systematic review of randomized, controlled trials and observational studies published through December 2015 that examined the comparative effectiveness of oral medications for type 2 diabetes.
The researchers evaluated metformin, thiazolidinediones, sulfonylureas, DPP-4 inhibitors, and SGLT-2 inhibitors. They examined intermediate outcomes of hemoglobin A1c, weight, systolic blood pressure, and heart rate, as well as outcomes of all-cause mortality, cardiovascular and cerebrovascular morbidity and mortality, retinopathy, nephropathy, and neuropathy.
In its first recommendation, the ACP noted that metformin should be prescribed to patients who need pharmacologic therapy to improve glycemic control (Grade: strong recommendation; moderate-quality evidence). They add that metformin is effective for reducing glycemic levels, is associated with weight loss and fewer hypoglycemic episodes, and is cheaper than most pharmacologic agents.
The ACP stated in its second recommendation that clinicians should consider a sulfonylurea, a thiazolidinedione, a SGLT-2 inhibitor, or a DPP-4 inhibitor if a second oral therapy is needed (Grade: weak recommendation; moderate-quality evidence). Combination therapies with metformin were shown to be more effective than metformin monotherapy in reducing HbA1c levels, weight, and blood pressure.
However, combination therapies were also associated with a greater risk of adverse effects compared with monotherapy. According to the FDA, DPP-4 inhibitors saxagliptin and alogliptin may increase risk of heart failure. In addition, SGLT-2 inhibitors are associated with an increased risk for genital mycotic infections, and sulfonylureas are associated with an increased risk of hypoglycemia.
“Oral pharmacologic therapy with metformin (unless contraindicated) is an effective management strategy,” the authors of the guideline wrote. “It is cheaper and more effective than most other pharmacologic agents and is associated with fewer adverse events; of note, it does not result in weight gain.
“Adding a second agent to metformin may provide additional benefits,” they added. “However, the increased cost may not always support the added benefit, particularly for the more expensive, newer medications.”
- Qaseem A, Barry MJ, Humphrey LL, Forciea MA. Oral pharmacologic treatment of type 2 diabetes mellitus: A clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2016. doi:10.7326/M16-1860