Comparing Medications for Type 2 Diabetes: What's Known

Charles P. Vega, MD


August 30, 2011

In This Article


The current review has some limitations. As noted above, the results may or may not be applicable to older adults or to racial or ethnic minorities. Furthermore, most patients receiving treatment for diabetes require years and years of therapy, something that is not reflected in the trials reviewed in the current study. Finally, the current study was limited to clinical research comparing active treatments for diabetes. Inclusion of placebo-controlled studies may have pushed data toward or away from statistical significance, particularly with regard to safety of the treatment regimens.

The current study suggests that metformin is a worthy first-line agent for the treatment of diabetes. Adding another oral medication or a GLP-1 receptor agonist to metformin reduces A1c to a similar degree, regardless of the drug choice.

Although sulfonylureas can reduce A1c to similar levels compared with other medications, physicians should use caution with these drugs, particularly among patients with a history of coronary artery disease. A retrospective study of over 11,000 patients found that older agents such as glyburide and glipizide may increase the risk for mortality compared with glimepiride among these patients.[7] However, this study found no increased risk for death in comparing these sulfonylureas in the larger study cohort. A study from France had similar findings.[8]

Physicians need to be sensitive regarding the use of sulfonylureas at least in part because of the emerging literature regarding health risks associated with hypoglycemia. In an analysis of a large prospective study of intensive glycemic control, researchers found that severe hypoglycemia was associated with a higher risk for major macrovascular events, microvascular events, and cardiovascular as well as overall mortality.[9] However, it was unclear whether hypoglycemia contributed to these negative outcomes or if it simply served as a marker for frail patients at higher risk for adverse outcomes.

These important findings in the care of patients with diabetes beg a larger question: just what is the ideal treatment target? While epidemiologic studies suggest that tighter control is superior for improving both microvascular and macrovascular outcomes, clinical trials are not as supportive of this finding. Moreover, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was stopped early due to a higher rate of mortality in the intensive vs standard glycemic control arm of the study.[10]

Recommendations from the American Diabetes Association, the American College of Cardiology Foundation, and the American Heart Association do an admirable job in parsing the conflicting data and providing guidelines that clinicians can use in everyday practice.[11] For most patients with type 2 diabetes, an A1c goal of less than 7% is sufficient. For patients at high risk for complications, including older adults, those with established complications of diabetes or cardiovascular disease, and those with a history of severe hypoglycemia, an A1c target of less than 7% is particularly prudent. However, for younger and otherwise healthy patients, a lower A1c target may improve the long-term risk for diabetes complications, particularly nephropathy.


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