Metformin MOA

10 Metformin MOA (Mechanism of Action) Key Takeaways

If you’re looking for the Metformin MOA (mechanism of action) you’ve come to the right place. I’m going to give you all the ins and outs on metformin. Which is considered the gold standard of type 2 diabetes therapy.

What is Metformin

First off, metformin (Glucophage and Glucophage XR) is the only drug in the biguanide class of drugs. Its cousin phenformin, was pulled from the market in the US during the early 1970s due to lactic acidosis.

In 2001, metformin was released under the brand name Glucophage XR, which was an extended release formulation of the drug.

NOTE: Metformin is associated with weight loss and I’ll tell you why in a minute. Most doctors expect their patients to lose weight on the drug and as a result improve glycemic control.

10 Metformin MOA Key Takeaways

1) Metformin’s mechanism of action is not well understood.

2) Metformin lowers blood glucose output from the liver, by decreasing gluconeogenesis (the production of new glucose from amino acids in the liver) and the breakdown of stored glucose in patients with type 2 diabetes.

3) Metformin decreases absorption of sugar (glucose) in the intestines and increases insulin sensitivity by increasing glucose uptake (amount of glucose that goes into bloodstream) and the ability of the muscle and fat tissue to use glucose.

4) Monotherapy (using metformin alone without other drugs) has been shown to lower fasting blood sugar levels by 40–70 mg/dl and A1C levels by 1.2–2.0 percentage points.

5) Based on extensive studies, metformin is considered a first-line oral drug for type diabetes when diet and exercise alone can get the job done at controlling your blood sugar levels.

6) This drug is effective in roughly 90% of patients. And it usually fails to maintain blood sugar control in 5–10% of patients per year. Like all drugs, metformin also fails to maintain blood sugar control over time.

7) This agent does cause gastrointestinal upset in 30% of patients and this is the most common side effect. These symptoms include diarrhea, abdominal pain, nausea, and anorexia. Many contribute these side effects as the reason why people lose weight on the drug.

8) Like phenformin, this drug does carry a risk to lactic acidosis. For this reason there is a black box warning with metformin. Although lactic acidosis is rare, it was found to be fatal in 50% of the cases.

9) Lactic acidosis can happen when metformin builds up in the blood. And this is more likely to happen if the kidneys aren’t functioning properly. Metformin is eliminated in the urine.

10) People with kidney problems (creatinine levels > .7–1/.5 mg/dl) should avoid taking metformin because of the increased risk to lactic acidosis. Metformin should also be used with caution in older people. Metformin should also be avoided in people with liver disease, which can increase the risk to lactic acidosis.


Metformin’s mechanism of action works primarily in the liver. It decreased the liver’s output of glucose and reduces glucose absorption in the intestines. It’s long been considered the gold standard and has been around for a while.

Usually the newer drugs work better than the older drugs. But the one nice thing about metformin is it has withstood the test of time. So physicians know what to expect.

If you have liver or kidney dysfunction your doctor will probably not put you on this drug. Mostly due to the risk of lactic acidosis. Aside from that, metformin’s MOA make it effective at controlling blood sugar. But it shouldn’t be relied on as the end all be all long term.

I’ll leave you with a great video on how metformin works in the body. Enjoy!

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