Does Lipitor Cause Weight Gain?

In our latest question and answer, the pharmacist discusses whether or not Lipitor (atorvastatin) can cause weight gain.

Does Lipitor Cause Weight Gain?
Mar 10, 2018

Greta asked

Does Lipitor cause weight gain?

Answer

Lipitor Weight GainAtorvastatin (Lipitor) has been associated with a small weight gain in at least one study, but it is unclear if this is caused directly by the drug or something else. Lipitor and other statins have been proven in multiple studies to reduce the risk of cardiovascular disease and death so the benefits largely outweigh the risks for most patient. Actively managing body weight should always be a significant part of managing chronic diseases like diabetes and heart disease.

A total of over 7,500 patients were studied in the Treating to New Targets (TNT) study and were analyzed for new onset diabetes and weight gain. Overall, after almost 5 years about 8-9% of patients on Lipitor developed diabetes. Additionally, there was an average increase in body weight of 0.9 kg (~2 pounds) after one year. Another study showed that the risk of developing diabetes was 6.1% on Lipitor vs 3.8% with placebo.

Despite these statistics, the absolute risk of developing diabetes and weight gain in patients on Lipitor is low and no change to clinical practice is recommended in moderate to high risk cardiovascular disease patients. Patients with a low risk for cardiovascular disease would have to consider the risk vs benefit.

Lipitor (Atorvastatin) - Additional Information

Lipitor (atorvastatin) is a statin medication, otherwise known as an HMG-CoA reductase inhibitor. Lipitor gradually decreases the amount of total cholesterol, LDL cholesterol (known as “bad” cholesterol), and triglycerides.

While the medication starts working within a few hours, it will probably take at least two weeks before any impact on cholesterol levels will be significant. Generally, lipid concentrations can be checked after 2-4 weeks. The dose can be gradually increased until the desired effect. Atorvastatin can reduce LDL levels by up to 45-60%. Atorvastatin 40-80 mg is considered a high intensity statin per the American College of Cardiology and American Heart Association.

Lipitor is rapidly absorbed within about 1 or 2 hours. Food may decrease the absorption, but does not seem to impact the reduction in cholesterol. While many statins are recommended to be taken in the evening, Lipitor can be taken at any time of day. Lipitor has a half-life of about 14 hours, but continues to work for 20-30 hours due to its active metabolites.

Lipitor is metabolized by several processes, especially CYP3A4, P-glycoprotein, and OATP1B1. The most significant drug interactions with Lipitor come with medications that reduce or increase the activity of CYP3A4. CYP3A4 is the most common enzyme responsible for breaking down medications. Many drug interactions are due to inhibition or induction of CYP3A4 and other CYP enzymes.

Inhibiting the enzyme allows for drugs that require CYP metabolism to stay in the body longer at a higher concentration. Inhibitors can increase the effect of Lipitor, which may lead to side effects like muscle pain and a severe condition known as rhabdomyolysis. Examples of CYP3A4 inhibitors include diltiazem, digoxin, grapefruit, and many HIV medications.

Per the Lipitor package insert, one study showed that drinking one glass of grapefruit juice (8 ounces) with atorvastatin resulted in an increased drug concentration of 37%. Drinking excessive amounts of grapefruit (approximately 1 L/day) increased drug concentrations 250%. Avoid grapefruit juice to avoid risk of side effects.

Inducing the enzyme would cause rapid metabolism of the drug and would therefore diminish its effect. CYP3A4 inducers reduce the activity of Lipitor. Examples of CYP3A4 inducers include some antiepileptics and rifampin.

Summary

  • Lipitor (atorvastatin) is associated with a small increase in body weight (around 2 pounds after 1 year) but studies aren't conclusive.
  • Lipitor (atorvastatin) is associated with an increased risk of diabetes versus placebo.
  • The benefits vs. risks of Lipitor (atorvastatin) need to be weighed in those with low cardiovascular risk.

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