The American College of Physicians (ACP) recommends that clinicians prescribe metformin to patients for glycemic control based on a systematic review of randomized, controlled trials and observational studies. The guideline, released January 3, 2017, serves as an update to the 2012 ACP guideline on the same topic. The oral pharmacologic agents evaluated include metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium–glucose cotransporter-2 (SGLT-2) inhibitors.Type II diabetes mellitus is a long-term metabolic disorder characterized by high blood sugar, insulin resistance, and relative lack of insulin. As of 2010, it was estimated that there were 285 million people with type 2 diabetes globally, making up about 90% of diabetes cases. Long-term complications include stroke, heart disease, kidney failure, diabetic retinopathy, and amputations.
Of the oral pharmacologic agents, studies revealed the DPP-4 inhibitors were inferior to metformin and sulfonylureas in reducing HbA1c levels, however, metformin also had a greater benefit on weight loss than all agents except the SGLT-2 inhibitors. SGLT-2 inhibitors, apart from lowering HbA1c were more effective than metformin in reducing blood pressure and combination therapies with metformin and an SGLT-2 or a DPP-4 inhibitor were superior to metformin alone in reducing HbA1c levels, weight, and blood pressure. When comparing combination therapies, metformin plus an SGLT-2 inhibitor was superior to metformin plus a DPP-4 inhibitor or metformin plus a sulfonylurea in reducing HbA1c levels.
Metformin alone was associated with a low risk for hypoglycemia while sulfonylureas, which were as effective as metformin in reducing HbA1c levels, increased the risk for hypoglycemia. Thiazolidinediones were associated with increased risk for congestive heart failure and both thiazolidinediones and sulfonylureas were associated with weight gain. SGLT-2 inhibitors increased the risk for genital mycotic infections and the DPP-4 inhibitors saxagliptin and alogliptin may increase the risk of heart failure, especially in patients who already have heart or kidney disease.
Taking into consideration all the following data, the ACP recommends that clinicians prescribe metformin to patients with type 2 diabetes when pharmacologic therapy is needed to improve glycemic control. It proved to be highly effective in reducing glycemic levels, it has the added benefit if weight loss and fewer hypoglycemic episodes when compared to the other agents. Therefore, unless contraindicated, metformin is the drug of choice for the treatment of patients with type 2 diabetes in addition to lifestyle modification, dietary modifications, regular exercise, and weight loss.
Metformin is contraindicated in patients with decreased tissue perfusion or hemodynamic instability, advanced liver disease, alcohol abuse, acute unstable congestive heart failure, or any condition that might lead to lactic acidosis. However, the FDA recently concluded that metformin is safe in patients with mild kidney impairment and in some patients with moderate kidney impairment.
When additional pharmacologic agents are needed to improve glycemic control, the ACP recommends that clinicians consider adding a sulfonylurea, a thiazolidinedione, an SGLT-2 inhibitor, or a DPP-4 inhibitor to metformin. Clinicians and patients should select the proper medications after discussing benefits, adverse effects, and costs and despite oral agents and lifestyle interventions insulin therapy may be required.
- Qaseem A, Barry MJ, Humphrey LL, Forciea MA, for the Clinical Guidelines Committee of the American College of Physicians. Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med. [Epub ahead of print 3 January 2017] doi: 10.7326/M16-1860
- ACP Updates Guidelines for Type 2 Diabetes Care. Medscape. Jan 03, 2017.