Medication Interactions With Grapefruit

Why does grapefruit interact with some medications?

Here’s what happens: Grapefruit contains furanocoumarins, a type of organic chemical compound that inhibits the efficacy of an important enzyme, called CYP3A4. This enzyme normally helps your body process the medication you take, balancing out how much of it goes into your bloodstream. Because furanocoumarins hinder this enzyme, larger amounts of the drug persist in your bloodstream and medication levels can grow toxic in the body.

And it doesn’t take much. One whole grapefruit or one glass of grapefruit juice is enough to alter how these medications affect you. It’s not just grapefruit, either. Other citrus fruits such as Seville oranges (often used in marmalade), limes and pomelos also contain furanocoumarins, but none of these have been as widely studied as grapefruit.

What does this mean for people with diabetes?

Currently, two drugs used to treat diabetes – repaglinide (GlucoNorm®) and saxagliptin (Onglyza®) – have been shown to interact with grapefruit. Their respective product monographs state the plasma concentrations of the drug rose after grapefruit was consumed. Saxagliptin is part of a class of medications called DPP-4 inhibitors. Other DPP-4 inhibitors have not been thoroughly studied but may also be affected by grapefruit. If you are taking any of these medications, you should speak with your healthcare team about whether and when you should consume grapefruit.

Metformin, SLGT-2 inhibitors (examples include empagliflozin, dapagliflozin), GLP-1 receptor agonists (examples include semaglutide, liraglutide), and insulin are generally safe to take with grapefruit. These drugs are not metabolized by CYP3A4, so grapefruit does not affect them.