Metformin and Thiazolidinediones Increase Anemia Risk

Oral medications are an important part of many diabetes treatment plans. Metformin, glipizide, pioglitazone, and others help those living with type 2 lose weight, increase insulin secretion, and lower blood glucose levels.

But more and more studies are linking some of these medications with lowered hemoglobin and anemia.

Before you ditch these beneficial meds, it is important to understand these recent findings and how you can help protect yourself from these potential side effects.

Metformin and Anemia Risk

An evaluation of multiple real-world population studies looking at the link between metformin and anemia was recently published in Diabetes Care.

• The first data reviewed came from the ADOPT study, which found that people on metformin were twice as likely to develop anemia compared to those on sulfonylureas alone. This reduction in hemoglobin was detectable at the first blood test, taken 6 months after each subject began oral medication treatment.
• Compared to people being treated for their diabetes with diet alone, the UKPDS study found that those on metformin were about 4.5 times more likely to develop anemia.

The annual risk for anemia increased by 2% for every 1g of metformin taken per day.

A reduction in hemoglobin was immediately apparent after metformin treatment began, but the decline appeared to level out soon after, with no further decrease noted after the three-year measurement in these studies.

While the risk for anemia was high, what was seen was largely moderate level anemia.

Compared to metformin, those on sulfonylureas and insulin both had a lower incidence of anemia, while those taking thiazolidinediones had significantly higher rates of anemia.

Thiazolidinediones, Anemia Risk, and Bone Marrow Suppression

Pioglitazone and rosiglitazone, sold under the brand names Actos and Avandia, appeared to have the highest associated risk for anemia out of all the diabetes treatments investigated in these studies.

• Compared to metformin, those on thiazolidinediones were twice as likely to develop anemia.
• This risk jumped to four times as likely when compared to those on sulfonylureas alone.
• Unlike metformin, anemia is a well-known side effect of this drug class. 

For a long time, it was assumed the reduced hemoglobin measurements seen in those taking the drug was an effect of increased fluid retention. However, more in-depth studies examining total body water, extracellular water, and fat-free mass in individuals on thiazolidinediones, found that fluid retention did not increase in those showing signs of anemia.

However, the researchers did find that a decline in white blood cell and platelet counts was detectable after subjects began this medication. This led researchers to conclude that the more likely source for anemia in these patients is a mild bone marrow suppressive effect.

Reducing Your Risk

As scary as anemia and suppressed bone marrow function sound, the fact is, both metformin and thiazolidinediones are effective tools for lowering blood sugar. And, in many cases, the benefits of using them far outweigh the risks.

Still, it is important that you and your doctor are aware of these potential side effects and act accordingly.

Here are some tips for keeping yourself safe and healthy while taking these drugs:

• Tell your doctor if you have a history of anemia so you can both decide if taking one of these medications is worth the risk, or if there are better options for you available.
• Know the signs of anemia: Dizziness, shortness of breath, pale skin, chest pain, cold hands/feet, rapid pulse, and low body temperature.
• Make sure your iron intake is high enough to support healthy hemoglobin levels. If you have kidney disease, it may be safer to take injectable iron rather than an oral supplement.
• Get your blood work done frequently to check for anemia. While it is unlikely that metformin would continue to drop your hemoglobin count, it is possible that other conditions could compound this issue and make it worse.
• Metformin is also known to cause B12 deficiency. While researchers don’t believe this complication plays into the anemia side effect seen with the drug, low B12 levels can cause anemia on their own, so it is important to assess your levels and supplement accordingly.

Beyond the above tips, it is good to keep in mind that abnormal hematocrit levels can affect the accuracy of your glucose meter. If you develop low hematocrit, as is common with these drugs, check the hematocrit range for your particular meter type.

You may have to change meters or work with your doctor to assure the blood glucose readings you are getting at home are accurate.