Metformin is a prescription medication used primarily in the management of type 2 diabetes. This pill is sold under brand names such as Glucophage and Riomet. A member of the drug group known as biguanides, this drug’s 500 mg tablet is the smallest available pill -- and a common starting dose for this first-line diabetes medication. This widely used medication is an effective tool to help lower blood glucose levels, used alone or in conjunction with other pills or insulin. However, metformin can also produce adverse effects.
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Gastrointestinal Side Effects
The most common side effects from metformin use include gastrointestinal (GI) discomfort, including diarrhea, nausea, vomiting, gas and abdominal pain. A diabetes prevention trial, published in the April 2012 issue of “Diabetes Care,” noted that over a 4-year period, 9.8 percent of metformin users reported GI side effects, while only 1.1 percent of those using placebo had these adverse effects. These side effects usually occur at the beginning of metformin therapy and go away as the body becomes adjusted to the medication. Taking the metformin with food and having the dose gradually increased also helps minimize these adverse effects. Extended-release tablets, such as metformin XR (Glucophage XR, Glumetza or Fortamet) may be easier on the stomach -- and an option for anyone who has these common metformin side effects.
Other Less Common Side Effects
As with most medications, the potential list of side effects is lengthy. Insight into the adverse reactions experienced by metformin users was noted in an analysis of multiple studies published in the February 2012 issue of “Diabetes Care.” While less common than GI discomfort, other potential metformin side effects include dizziness, headache, palpitations, urinary tract infection, hypertension and coughing. Food and Drug Administration (FDA) prescribing information, pubished on DailyMed, outlines other side effects that have occurred in less than 5 percent of users, including abnormal stools, muscle aches, labored breathing, nail changes, rash, increased sweating, taste changes, chest discomfort, general feeling of discomfort and flushing. As with the GI side effects, the occurrence of these side effects can be dose-related.
Anemia and Low Blood Sugar
Metformin use has been associated with an increased risk of anemia related to vitamin B12 deficiency. An analysis of 6 studies, published in the June 2014 issue of “PLoS One,” concluded that metformin could reduce vitamin B12 levels, and that well-designed research trials are needed to confirm these findings. Of note, metformin is also available in 850 mg and 1000 mg tablets with a maximum daily dose of 2550 mg, and this research analysis determined that reduction in vitamin level was dose-related.
Hypoglycemia, or low blood glucose, is also a noted side effect, according to the February 2012 issue of “Diabetes Care.” However, hypoglycemia is a rare side effect of metformin-only use, as this drug’s mechanism of action does not increase blood insulin levels. Hypoglycemia is a more likely side effect when metformin is combined with other diabetes medications, such as insulin or sulfonylureas -- pills that increase insulin production in the body.
Because metformin increases blood lactate levels, metformin-associated lactic acidosis (MALA) is a rare yet life-threatening adverse effect, occurring in less than 10 people per every 100,000 users per year, according to a report in the February 2016 issue of “Metabolism.” MALA is a risk when metformin or lactate doesn’t get properly cleared from the blood, as in severe kidney or liver disease or in situations where there is a potential for declined kidney function -- including surgery, severe illness or the use of contrast dye for imaging studies. Congestive heart failure, excessive alcohol use, severe blood infection or advanced age can also increase the risk of MALA. This can produce symptoms such as a breathing problems, dizziness, irregular heartbeat and severe weakness, and urgent medical treatment is necessary to manage this condition.
Warnings and Precautions
Metformin is a widely used and often well-tolerated medication. GI symptoms are common but often temporary, although some people taking metformin may have persistent side effects. Most of metformin's adverse reactions are dose-related, with the 500 mg tablet offering the potential of fewer side effects. Despite the rare risk of MALA, the FDA provides evidence-based prescribing guidelines for doctors to use to minimize this risk. These guidelines include, for example, contraindicated levels of kidney function, indications for stopping prior to surgery and recommendations for ongoing monitoring of kidney function. Talk to your doctor if you have concerns about the use of metformin or if you are experiencing any side effects.
- Diabetes Care: Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study
- International Journal of Endocrinology: Pharmacogenetics of Oral Antidiabetic Drugs
- PLoS One: Vitamin B12 Status in Metformin Treated Patients: Systematic Review
- Metabolism: Metformin-Associated Lactic Acidosis: Current Perspectives on Causes and Risk.
- Diabetes Care: Quantifying the Effect of Metformin Treatment and Dose on Glycemic Control
- DailyMed: Metformin HCL