Drug & supplement interaction

Clove + pioglitazone, metformin

pioglitazone, metformin brand name: ActoPlus Met.

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

pioglitazone, metformin falls into 2 drug categories that Clove can interact with; the most serious is rated moderate. Theoretically, concomitant use of clove extracts with antidiabetes drugs might increase the risk of hypoglycemia.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Clove and pioglitazone, metformin

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

Why Are There 2 Interactions?

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

Moderate

ANTIDIABETES DRUGS

1 of 2

Why this applies to pioglitazone, metformin

pioglitazone, metformin falls under ANTIDIABETES DRUGS — the group Clove interacts with.

Theoretically, concomitant use of clove extracts with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical and laboratory research suggest that polyphenol extracts from clove flower buds might lower blood glucose levels. Dosing adjustments for insulin or oral hypoglycemic agents may be necessary when taken with clove. Monitor blood glucose levels closely.
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

Here's the simple version: your ActoPlus Met (pioglitazone plus metformin) already works to bring your blood sugar down. Some lab and early research hints that concentrated clove extracts might also nudge blood sugar a little lower on their own. Stack the two together, and in theory you could dip too low, which we call hypoglycemia. That can show up as shakiness, sweating, dizziness, a fast heartbeat, or feeling confused or unusually hungry.

I want to be honest about the strength here: this is theoretical, based on how clove behaves, not proven in people. The clove you sprinkle in cooking is very unlikely to matter. Concentrated clove oil or supplements are the real question. If you want to try them, just check with your pharmacist or doctor first and keep an eye on your glucose readings.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mohan R, Jose S, Mulakkal J, Karpinsky-Semper D, Swick AG, Krishnakumar IM. Water-soluble polyphenol-rich clove extract lowers pre- and post-prandial blood glucose levels in healthy and prediabetic volunteers: an open label pilot study. BMC Complement Alt PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

pioglitazone, metformin also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP3A4.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP3A4 in a dose-dependent manner. This effect 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

Here's the short version on ActoPlus Met, which combines pioglitazone and metformin. Lab studies suggest that eugenol, the main oil in clove, can slow down a liver enzyme called CYP3A4. Of these two medicines, only pioglitazone leans on that enzyme to be cleared from your body. So in theory, large amounts of clove could let pioglitazone build up a bit, which might nudge its effects up: more chance of fluid retention, swelling in the ankles, weight gain, or low blood sugar (especially if you take other diabetes meds).

Now the reassuring part. This is only seen in test tubes, not in real people, and metformin isn't affected by this pathway at all. Cooking with clove is a non-issue. If you're using concentrated clove oil or capsules daily, just mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alharbi NFM, Ahad A, Bin Jardan YA, Al-Jenoobi FI. Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes. Saudi Pharm J 2024;32(7):102118. 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

Clove Also Interacts With Other Medications

Clove has 916 moderate, 60 minor known drug interactions in our database — the pioglitazone, metformin one above is among them. If you take anything else, check it against the full list below.

Moderate 916 Minor 60 No known interaction 1,854 (incl. pioglitazone, metformin)
Taking anything else?

Check Another of Your Medications Against Clove

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

Everything else you take

See Every Supplement That Interacts With pioglitazone, metformin

This page covers Clove only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the pioglitazone, metformin page lists 357 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 311 moderate · 40 minor.

From our pharmacist’s overview on the pioglitazone, metformin page

“ActoPlus Met pairs pioglitazone with metformin for type 2 diabetes, and the size of this list, 357 supplements in all, reflects how many herbs lower blood sugar on their own. Stacked with the drug, they can push glucose too low; most of the 311 moderate entries work exactly that way.”

Reviewed by 2 · Jul 18, 2026

Open the pioglitazone, metformin interaction page

One more smart check

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

We hold 59 real supplement products containing Clove, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Clove. Your product may carry other ingredients that interact with pioglitazone, metformin too, on top of Clove — 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 Clove and pioglitazone, 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 Clove
Top 25%

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

29 days ago today
Medication pioglitazone, metformin
Steady interest

#2,029 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 Clove

What is Clove?

Clove
  • Toothache and oral pain
  • Digestive upset
  • Antimicrobial and antifungal
  • Cough and respiratory complaints
  • Flavoring in food and drinks

Clove is a common cooking spice that is also used in traditional medicine, especially as a topical numbing agent for tooth pain thanks to its main compound, eugenol. Food amounts are generally safe, but concentrated clove oil and supplements can be irritating or toxic if overused, and human evidence for most health claims is limited. Talk to your pharmacist or doctor before using clove medicinally, especially in children or during pregnancy.

Read the full Clove monograph & all interactions
Keep checking

Other Drugs & Clove

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

0Major
916Moderate
60Minor
1,853No known interaction
916 Moderate 60 Minor 1,853 No interaction
Moderate

916 interactions

Showing 60 of 916 moderate interactions — see all 916 on the Clove page.

Minor

60 interactions

No interaction 1,853 drugs checked — show the list

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

Showing the 60 most looked-up of 1,853 medications checked with no known interaction — see the full Clove list.

See the full Clove interactions page
See every supplement checked against pioglitazone, 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
Clove monograph › Uses, safety, and every drug interaction in one place pioglitazone, metformin supplement interactions › Every supplement checked against pioglitazone, 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 Clove and pioglitazone, metformin Together: Common Questions

Can you take Clove with pioglitazone, metformin?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Clove and pioglitazone, metformin?
pioglitazone, metformin belongs to more than one drug category, and Clove 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 Clove and pioglitazone, metformin interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About pioglitazone, metformin and Clove?

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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.