Drug & supplement interaction

Grapefruit + Glyburide, Metformin

Glyburide, Metformin brand name: Glucovance.

Major Interaction
Medically reviewed by · Updated September 2026
The bottom line Major

Glyburide, Metformin falls into 2 drug categories that Grapefruit can interact with; the most serious is rated major. Grapefruit juice can decrease levels of drugs that are substrates of OATP.

Read the full interaction report
SeverityMajor
LikelihoodLikely
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grapefruit and Glyburide, Metformin

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Grapefruit interacts with whole categories of medication. Glyburide, Metformin falls into 2 of those categories, so it can interact with Grapefruit in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

1 of 2

Why this applies to Glyburide, Metformin

Glyburide, Metformin falls under ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) — the group Grapefruit interacts with.

Grapefruit juice can decrease levels of drugs that are substrates of OATP.
In vitro and clinical research show that consuming grapefruit juice inhibits OATP, which reduces the bioavailability of oral drugs that are substrates of OATP. Various clinical studies have shown reduced absorption of OATP substrates when taken with grapefruit, including fexofenadine, acebutolol, aliskiren, celiprolol, levothyroxine, nadolol, and pitavastatin. Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction.
Severity Major Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for your Glucovance (glyburide plus metformin): grapefruit juice can temporarily block a transporter called OATP that helps your gut absorb certain medicines. When that happens, less of the drug may make it into your bloodstream. In practical terms, that could mean your blood sugar isn't controlled as well as expected, so you might see higher readings if grapefruit blunts how much of this combo you absorb.

The good news is the effect is short-lived. Spacing your grapefruit or grapefruit juice at least 4 hours apart from your dose usually sidesteps the problem. The evidence here is moderate, and it applies more to regular grapefruit juice than an occasional bite of fruit. Since blood sugar control matters, please run your grapefruit habit by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Greenblatt DJ. Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides. J Clin Pharmacol 2009;49:1403-7. PubMed
  2. Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol 2010;70:645-55. PubMed
  3. Lilja JJ, Raaska K, Neuvonen PJ. Effects of grapefruit juice on the pharmacokinetics of acebutolol. Br J Clin Pharmacol 2005;60:659-63. PubMed
  4. Ando, H., Tsuruoka, S., Yanagihara, H., Sugimoto, K., Miyata, M., Yamazoe, Y., Takamura, T., Kaneko, S., and Fujimura, A. Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin. Br J Clin Pharmacol 2005;60(5):494-497. DOI
  5. Lilja, J. J., Backman, J. T., Laitila, J., Luurila, H., and Neuvonen, P. J. Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol. Clin Pharmacol Ther 2003;73(3):192-198. PubMed
  6. Glaeser, H., Bailey, D. G., Dresser, G. K., Gregor, J. C., Schwarz, U. I., McGrath, J. S., Jolicoeur, E., Lee, W., Leake, B. F., Tirona, R. G., and Kim, R. B. Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharma PubMed
  7. Lilja, J. J., Laitinen, K., and Neuvonen, P. J. Effects of grapefruit juice on the absorption of levothyroxine. Br J Clin Pharmacol 2005;60(3):337-341. PubMed
  8. Hu M, Mak VW, Yin OQ, Chu TT, Tomlinson B. Effects of grapefruit juice and SLCO1B1 388A>G polymorphism on the pharmacokinetics of pitavastatin. Drug Metab Pharmacokinet. 2013;28(2):104-8.
  9. Tanaka S, Uchida S, Miyakawa S, Inui N, Takeuchi K, Watanabe H, Namiki N. Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4. Biol Pharm Bull. 2013;36(12):1936-41. PubMed
  10. Tapaninen T, Neuvonen PJ, Niemi M. Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren. Clin Pharmacol Ther. 2010 Sep;88(3):339-42. PubMed
  11. Piscitelli J, Nikanjam M, Capparelli EV, et al. Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach. Ther Drug Monit 2023;45(4):539-545. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

Glyburide, Metformin also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C9.
In vitro research suggests that grapefruit juice might inhibit CYP2C9 enzymes. So far, this interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Glucovance combines two diabetes medicines. The one that matters here is glyburide, which your liver clears using an enzyme called CYP2C9. In test-tube studies, compounds in grapefruit appear to slow that enzyme down. If that happened in your body, glyburide could hang around longer and push your blood sugar lower than expected. That can mean shakiness, sweating, dizziness, or feeling lightheaded. The metformin half is not really affected this way.

I want to be straight with you though: this is only lab evidence, and it has not actually been seen in people. An occasional grapefruit is unlikely to be a problem. Still, since hypoglycemia is serious, check with your pharmacist or doctor before making grapefruit a regular habit.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Grapefruit Also Interacts With Other Medications

Grapefruit has 775 major, 151 moderate, 63 minor known drug interactions in our database — the Glyburide, Metformin one above is among them. If you take anything else, check it against the full list below.

Major 775 Moderate 151 Minor 63 No known interaction 1,841 (incl. Glyburide, Metformin)
Taking anything else?

Check Another of Your Medications Against Grapefruit

Covers the 2,830 medications we’ve checked against Grapefruit. Pick one to open its full report.

From our Q&A

Questions About Grapefruit or Glyburide, Metformin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grapefruit or Glyburide, Metformin, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Glyburide, Metformin

This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Glyburide, Metformin page lists 332 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Siberian Cocklebur (major) and Sweet Orange (major).

By severity: 7 major · 281 moderate · 44 minor.

From our pharmacist’s overview on the Glyburide, Metformin page

“Glucovance combines glyburide and metformin to lower blood sugar, and its list of 332 interacting supplements deserves real care, starting with the seven rated major. Most entries, 239 of them, lower blood sugar on their own, so stacking one on top of a drug built to do exactly that can drop your glucose into dangerous territory.”

Reviewed by 2 · Jul 18, 2026

Open the Glyburide, Metformin interaction page

One more smart check

Taking Grapefruit as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,144 real supplement products containing Grapefruit, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grapefruit. Your product may carry other ingredients that interact with Glyburide, Metformin too, on top of Grapefruit — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Grapefruit and Glyburide, Metformin Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Grapefruit
Top 10%

#98 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Glyburide, Metformin
Top half

#1,412 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Grapefruit

What is Grapefruit?

Grapefruit
  • Source of vitamin C
  • Digestive complaints
  • Antimicrobial (seed extract)
  • Weight management
  • Skin and cosmetic uses

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription medicines, so anyone taking medication should check with a pharmacist or doctor before consuming it regularly.

Read the full Grapefruit monograph & all interactions
Keep checking

Other Drugs & Grapefruit

Browse every other medication we’ve checked against Grapefruit — both the ones with a known interaction and the ones without. Select any drug for the full detail.

775Major
151Moderate
63Minor
1,840No known interaction
775 Major 151 Moderate 63 Minor 1,840 No interaction
Major

775 interactions

Showing 60 of 775 major interactions — see all 775 on the Grapefruit page.

Moderate

151 interactions

Showing 60 of 151 moderate interactions — see all 151 on the Grapefruit page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Grapefruit page.

No interaction 1,840 drugs checked — show the list

We also checked Grapefruit against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.

See the full Grapefruit interactions page
See every supplement checked against Glyburide, Metformin, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Grapefruit monograph › Uses, safety, and every drug interaction in one place Glyburide, Metformin supplement interactions › Every supplement checked against Glyburide, Metformin, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Grapefruit and Glyburide, Metformin Together: Common Questions

Can you take Grapefruit with Glyburide, Metformin?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Grapefruit and Glyburide, Metformin?
Glyburide, Metformin belongs to more than one drug category, and Grapefruit interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Grapefruit and Glyburide, Metformin interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Glyburide, Metformin and Grapefruit?

Our pharmacists answer your medication & supplement questions — free.

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.