Drug & supplement interaction

Ilex Guayusa + pioglitazone, metformin

pioglitazone, metformin brand name: ActoPlus Met.

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

pioglitazone, metformin falls into 3 drug categories that Ilex Guayusa can interact with; the most serious is rated moderate. Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ilex Guayusa and pioglitazone, metformin

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Ilex Guayusa interacts with whole categories of medication. pioglitazone, metformin falls into 3 of those categories, so it can interact with Ilex Guayusa in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

PIOGLITAZONE (Actos)

1 of 3
Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
Ilex guayusa contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone. However, the exact mechanism of this interaction is unclear.
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 gist with your ActoPlus Met, which combines pioglitazone and metformin. The caffeine in guayusa may, in theory, slow down how your body clears the pioglitazone part, letting it build up a little and work a bit harder than expected. In practical terms, that could mean a stronger blood-sugar-lowering effect, so watch for signs of low blood sugar like shakiness, sweating, dizziness, or feeling unusually hungry or tired.

I want to be honest: this is based only on animal research, so it's far from proven in people, and an occasional cup is unlikely to cause trouble. Still, if you drink guayusa regularly or have had low sugar readings before, it's worth a quick chat with your pharmacist or doctor before making any changes.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Alshabi AM, Alkahtani SA, Shaikh IA, Habeeb MS. Caffeine modulates pharmacokinetic and pharmacodynamic profiles of pioglitazone in diabetic rats: Impact on therapeutics. Saudi Med J 2021;42(2):151-160. PubMed
Minor

ANTIDIABETES DRUGS

2 of 3

Why this applies to pioglitazone, metformin

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

Theoretically, taking Ilex guayusa with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research in a model of hyperglycemia suggests that Ilex guayusa may have antihyperglycemic effects, although it does not appear to lower glucose levels when compared with baseline. This effect has not been evaluated in humans.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

If you enjoy a cup of guayusa tea while taking ActoPlus Met (pioglitazone plus metformin), the worry here is pretty small. In animal studies, guayusa showed a mild blood-sugar-lowering effect, so the thinking is that combining it with diabetes medicines might nudge your sugar a little lower than the medicines alone. This is only a theory based on lab work, and it hasn't been confirmed in people.

Both of your medicines already work to bring glucose down, so just keep an eye out for signs of low sugar: shakiness, sweating, dizziness, or feeling foggy. If you notice that often, or you have any concerns, check in with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Swanston-Flatt SK, Day C, Flatt PR, Gould BJ, Bailey CJ. Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetes Res 1989;10(2):69-73.
  2. Mello TC, Dias DDS, Bernardes N, et al. Ilex Guayusa Tea Improves Glycaemia and Autonomic Modulation in Female Streptozotocin-Induced Diabetic Rats. Pharmaceuticals (Basel) 2025;18(3):316. PubMed
Minor

METFORMIN (Glucophage)

3 of 3
Theoretically, metformin might increase the levels and adverse effects of caffeine.
Ilex guayusa contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism. Theoretically, concomitant use can increase caffeine serum concentrations and the risk of caffeine adverse effects.
Severity Minor 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 thing to know about pairing guayusa tea with your ActoPlus Met (that's pioglitazone plus metformin): the concern isn't really about your diabetes medicine getting stronger or weaker. It's the other way around. Animal studies hint that the metformin part may slow down how fast your body clears caffeine, and guayusa is basically a caffeine source.

So in theory, the caffeine could hang around longer and hit harder. That might mean a jittery feeling, a racing heart, trouble sleeping, or feeling wound up. I'll be honest though, this is weak evidence from lab and animal work, not people, so for most folks a cup or two won't be a big deal. If you notice extra jitteriness or have heart concerns, just check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Mohiuddin, M., Azam, A. T., Amran, M. S., and Hossain, M. A. In vive effects of gliclazide and metformin on the plasma concentration of caffeine in healthy rats. Pak.J Biol Sci 5-1-2009;12(9):734-737.

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

Ilex Guayusa Also Interacts With Other Medications

Ilex Guayusa has 8 major, 469 moderate, 127 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.

Major 8 Moderate 469 Minor 127 No known interaction 2,226 (incl. pioglitazone, metformin)
Taking anything else?

Check Another of Your Medications Against Ilex Guayusa

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

Everything else you take

See Every Supplement That Interacts With pioglitazone, metformin

This page covers Ilex Guayusa 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

How much people look this up

Where Ilex Guayusa 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 Ilex Guayusa
Top half

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

29 days ago today
Medication pioglitazone, metformin
Top half

#1,401 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 Ilex Guayusa

What is Ilex Guayusa?

  • Energy and alertness
  • Mental focus
  • Antioxidant support
  • Appetite control
  • Athletic and physical performance

Ilex guayusa is a caffeine-containing holly leaf from the Amazon, traditionally brewed as a tea for energy and alertness, much like yerba mate or green tea. There is limited human research confirming specific health benefits, and its main reliable effect comes from its caffeine content. Because it is a stimulant, use it cautiously and check with your pharmacist or doctor if you have heart concerns or are pregnant.

Read the full Ilex Guayusa monograph & all interactions
Keep checking

Other Drugs & Ilex Guayusa

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

8Major
469Moderate
127Minor
2,225No known interaction
8 Major 469 Moderate 127 Minor 2,225 No interaction
Major

8 interactions

Moderate

469 interactions

Showing 60 of 469 moderate interactions — see all 469 on the Ilex Guayusa page.

Minor

127 interactions

Showing 60 of 127 minor interactions — see all 127 on the Ilex Guayusa page.

No interaction 2,225 drugs checked — show the list

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

Showing the 60 most looked-up of 2,225 medications checked with no known interaction — see the full Ilex Guayusa list.

See the full Ilex Guayusa 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
Ilex Guayusa 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 Ilex Guayusa and pioglitazone, metformin Together: Common Questions

Can you take Ilex Guayusa 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 3 interactions listed for Ilex Guayusa and pioglitazone, metformin?
pioglitazone, metformin belongs to more than one drug category, and Ilex Guayusa 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 Ilex Guayusa 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

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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.