Metformin has highest benefit-risk profile in type 2 diabetes

Evidence supports metformin as a first-line agent to treat type 2 diabetes, according to a study in the March 14, 2011, online edition of the Annals of Internal Medicine.

Investigators from Johns Hopkins University School of Medicine in Baltimore and other centers determined that metformin, both as monotherapy and in combination with other medications, has the highest benefit–risk profile in most comparisons with other medications for diabetes.

Two reviewers, working independently, identified 140 trials and 26 observational studies of head-to-head comparisons of monotherapy or combination therapy that reported intermediate or long-term clinical outcomes or harms. The investigators found that most diabetes medications were similarly efficacious when used as monotherapy and decreased HbA1c levels by 1 absolute percentage point on average. However, metformin proved superior to dipeptidyl peptidase-4 (DPP-4) inhibitor in reducing HbA1c. Combination therapy, including that of metformin and DPP-4 inhibitor, decreased HbA1c  levels more than monotherapy did - by approximately 1 absolute percentage point.

There was a 4-fold higher risk of mild-to-moderate hypoglycemia associated with sulfonylureas compared to use of metformin alone; the risk increased to 5-fold when sulfonylureas were combined with metformin compared to a metformin-plus-thiazolidinediones combination.  In addition, metformin decreased low-density lipoprotein cholesterol (LDL-C) levels significantly compared to pioglitazone, sulfonylureas, and DPP-4 inhibitors. Most diabetes medications generally increased weight. Metformin, however, was consistently associated with weight reduction or was neutral.

Patients taking thiazolidinediones had an increased risk for congestive heart failure compared with those taking sulfonylureas and an increased risk for bone fractures compared to metformin. Diarrhea occurred more often in patients taking metformin than in those taking thiazolidinediones.