Metformin is a biguanide oral hypoglycemic used primarily for treating type 2 diabetes mellitus (T2D). Evidence suggests that, in addition to improving glycemic control, metformin is associated with improved all-cause and cardiovascular mortality and decreased risk of some cancers. However, clinicians have been advised by the U.S. Food and Drug Administration (FDA) to exercise caution in prescribing metformin to individuals with chronic kidney disease (CKD), unstable congestive heart failure (CHF), chronic liver disease (CLD), and older age due to perceived risk of side effects, including lactic acidosis (LA).
Recent literature highlights the rarity of metformin-associated LA and supports the cautious expansion of metformin use. In addition, in April 2016 the FDA modified its position on CKD to extend use of metformin to some patients with moderate CKD. Yet there remain uncertainties regarding the risks and benefits of metformin use in populations with CKD, CHF, CLD, and older age. For this reason, we conducted a systematic review and meta-analysis in order to determine the answers to the following key questions:
KQ 1. For patients with type 2 diabetes and an apparent contraindication or precaution to metformin use (eg, renal insufficiency, congestive heart failure, chronic liver disease, or older age):
What is the rate of lactic acidosis in patients taking metformin?
How does the rate of lactic acidosis in patients taking metformin compare with the rate in patients taking other hypoglycemics?
KQ 2. For patients with type 2 diabetes and an apparent contraindication or precaution to metformin use, what are the potential benefits and harms (other than lactic acidosis) of continued treatment with metformin?