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Breaking down diabetes: Drugs for diabetes, starting with the best — metformin

Metformin is physician-researcher Randall Stafford's go-to drug for diabetes. He explains why in this installment in the series, Breaking down diabetes.

Editors' note: We are revising two posts in the Breaking Down Diabetes series to reflect current findings on the most effective medications. The best place to begin the series is with the first post, On the road to diabetes: A look at what's happening inside the body

A huge assortment of 100 medications are available to treat high blood sugar in Type 2 diabetes, including two historical breakthrough drugs, insulin and metformin. The pharmaceutical industry has successfully added a few new, innovative drugs, but the most effective drugs remain the older, less expensive medications.

Let's make some sense out of this mess of medications.

Most are given by mouth (oral), but injected insulin, which I'll address in a future blog post, remains a key medication. In addition, oral drugs have limited impact, so they are often used in combinations (including tablets containing two drugs). Patients frequently try multiple oral drugs before starting insulin.

Metformin is my go-to drug 

With very few exceptions, I start patients on metformin first.

To illustrate a patient's experience with diabetes drugs, let's check in on with Mrs. R., a 70-year-old with diabetes:

When she was first diagnosed 19 years ago, she started on metformin at 500 mg twice per day. These large tablets initially caused intestinal discomfort (a common side effect). Over time, the mild abdominal pain went away. This drug worked well for a few years, but Mrs. R gained some additional weight and the metformin was no longer adequate. The drug, glipizide was added. This also worked for many years, but in 2012, she needed a third drug, sitagliptin. Eventually, she would need insulin.

To understand Mrs. R's experience, or the medications taken by you or a friend or family member, let's start with the best medication, metformin.

Approved by the U.S. Food & Drug Administration in 1994, metformin is so critical to diabetes treatment that if you don't tolerate it at first because of abdominal side effects, it's worth trying again. Many of my patients who did not tolerate this drug at first did better when they started at low doses and then worked to increase the amount they could easily tolerate.

This is my first-line, go-to drug for diabetes, and I'm always surprised when I encounter a patient with Type 2 diabetes who's not taking it. And, just to be clear, metformin is a generic and I have no financial interests related to its use. Interestingly, the origin of metformin can be traced back to a herbal remedy from French lilac that has been known since the Middle Ages.

Why metformin works

Here are just a few reasons metformin is so great:

  • It can help with weight loss, while nearly all other diabetes drugs cause weight gain.
  • Metformin reduces high blood sugar, but rarely lowers blood sugar to levels below normal. Most other drugs have the potential to cause life-threatening hypoglycemia (low blood sugar).
  • This drug can be continued even if it becomes necessary to start insulin.
  • It's inexpensive, costing pharmacies as little as $0.06 per day of treatment.

Metformin works by increasing the body's response to insulin, effectively reversing the insulin resistance that causes Type 2 diabetes. Insulin resistance occurs when the body's liver, muscle and fat cells require more and more insulin in the bloodstream to make them do their jobs.

It's no surprise that it is widely used, with 72% of U.S. diabetes patients who take medications on metformin. It could be used even more often. If you have Type 2 diabetes, you need to be on metformin or have a good reason not to take it (like advanced kidney disease). If you've tried it and have had indigestion or other abdominal problems, it may be worth trying this wonder drug again.

There are six other major classes of blood-sugar lowering drugs used in Type 2 diabetes. Of these, the SGLT2 inhibitors (short for sodium-glucose co-transporter) are emerging as the next best drug after metformin.  All of these medications can be combined with metformin to get blood sugar back towards normal levels. We will review these next-best drugs in the next blog post.

Randall Stafford, MD, PhD, a professor of medicine and director of the Program on Prevention Outcomes and Practices, practices primary care internal medicine at Stanford. He is developing practical strategies to improve how physicians and consumers approach chronic disease treatment and prevention.

This is the sixth piece in the series, "Breaking Down Diabetes," created for those with or at risk for diabetes as well as their family and friends. Previous blog posts addressed the pre-diabetes, diabetes complications, and goals for diabetes beyond blood sugar. Some data for this report come from IQVIA, Inc., previously known as QuintilesIMS. For additional information, please contact

Image by mcmurryjulie

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