Drug & supplement interaction

Yerba Mate + pioglitazone, metformin

pioglitazone, metformin brand name: ActoPlus Met.

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

pioglitazone, metformin falls into 4 drug categories that Yerba Mate can interact with; the most serious is rated moderate. Theoretically, the caffeine in yerba mate might increase the levels and clinical effects of pioglitazone.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Yerba Mate and pioglitazone, metformin

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Yerba Mate interacts with whole categories of medication. pioglitazone, metformin falls into 4 of those categories, so it can interact with Yerba Mate in 4 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 4
Theoretically, the caffeine in yerba mate might increase the levels and clinical effects of pioglitazone.
Yerba mate 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

Your medicine ActoPlus Met combines two diabetes drugs: pioglitazone and metformin. The interaction we have on file involves the pioglitazone piece. The thinking is that caffeine from yerba mate might slow how your body clears pioglitazone, so a little more could hang around. In theory that could push its blood-sugar-lowering effect a bit stronger, which means a slightly higher chance of low blood sugar (shakiness, sweating, dizziness, or feeling foggy).

Here is the honest part: this is based only on animal research, not solid human studies, so it is more of a theoretical heads-up than a proven problem. Enjoying mate in normal amounts is likely fine for most people. Still, if you drink a lot of it, mention it to your pharmacist or doctor so they can keep an eye on your numbers.

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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

Why this applies to pioglitazone, metformin

pioglitazone, metformin falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Yerba Mate interacts with.

Theoretically, yerba mate might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yerba mate extract inhibits CYP3A4 enzymes. Theoretically, taking yerba mate may increase levels and adverse effects of CYP3A4 substrates.
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 short version: this concern is mostly theoretical. In lab tests (not in real people), yerba mate appeared to slow down a liver enzyme called CYP3A4. The thinking is that if that enzyme runs slower, certain medicines it processes could build up a bit and cause stronger effects.

For your ActoPlus Met, though, this likely matters very little. Metformin isn't really broken down by the liver at all, it leaves your body through the kidneys, so CYP3A4 doesn't touch it. Pioglitazone does use liver enzymes, but mainly CYP2C8, not 3A4. Neither one is a prodrug. So a cup or two of mate isn't expected to cause problems. Just keep an eye out for low blood sugar signs (shakiness, sweating) and mention your mate habit to your pharmacist if you drink a lot.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Feltrin C, Farias IV, Sandjo LP, Reginatto FH, Simões CMO. Effects of Standardized Medicinal Plant Extracts on Drug Metabolism Mediated by CYP3A4 and CYP2D6 Enzymes. Chem Res Toxicol 2020;33(9):2408-2419. PubMed
Minor

ANTIDIABETES DRUGS

3 of 4

pioglitazone, metformin also falls under ANTIDIABETES DRUGS.

Theoretically, taking yerba mate with antidiabetes drugs might interfere with blood glucose control.
Yerba mate contains caffeine. Reports claim that caffeine might increase or decrease blood sugar.
Severity Minor Likelihood Unlikely Evidence B

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

Here's the simple version: ActoPlus Met (pioglitazone plus metformin) works to lower your blood sugar. Yerba mate brings caffeine to the table, and caffeine has been reported to nudge blood sugar in either direction, up or down, depending on the person. So in theory, sipping a lot of mate could make your glucose levels a little less predictable.

The good news is this is rated a minor and unlikely interaction, and the evidence behind it is thin. A cup or two of mate is very unlikely to throw off your numbers. If you drink it regularly or notice unusual highs, lows, shakiness, or sweating, just keep an eye on your readings and mention it to your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Watson JM, Jenkins EJ, Hamilton P, et al. Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes. Diabetes Care 2000;23:455-9. PubMed
  2. Bell DG, Jacobs I, Ellerington K. Effect of caffeine and ephedrine ingestion on anaerobic exercise performance. Med Sci Sports Exerc 2001;33:1399-403. PubMed
Minor

METFORMIN (Glucophage)

4 of 4
Theoretically, metformin might increase the levels and adverse effects of the caffeine in yerba mate.
Yerba mate contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism. However, this effect has not been reported in humans.
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 yerba mate with your ActoPlus Met (that's pioglitazone plus metformin): the concern isn't really about your diabetes control. It's about the caffeine in the mate. The metformin part may, in theory, slow down how your body clears caffeine. If that happens, the caffeine could hang around a bit longer and hit harder, leaving you feeling jittery, restless, or with a racing heart or trouble sleeping.

I'll be honest with you though, this is only seen in animal studies and has never actually been reported in people, so it's a very minor, mostly theoretical worry. Neither pioglitazone nor metformin is a prodrug, so the mate won't make your sugar meds stronger or weaker. If you notice more caffeine buzz than usual, just ease back on the mate and mention it to your pharmacist.

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

Yerba Mate Also Interacts With Other Medications

Yerba Mate has 8 major, 504 moderate, 573 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 504 Minor 573 No known interaction 1,745 (incl. pioglitazone, metformin)
Taking anything else?

Check Another of Your Medications Against Yerba Mate

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

Everything else you take

See Every Supplement That Interacts With pioglitazone, metformin

This page covers Yerba Mate 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 Yerba Mate as Part of a Dietary Supplement Product? Check It for Interactions

We hold 68 real supplement products containing Yerba Mate, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Yerba Mate. Your product may carry other ingredients that interact with pioglitazone, metformin too, on top of Yerba Mate — 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 Yerba Mate 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 Yerba Mate
Steady interest

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

29 days ago today
Medication pioglitazone, metformin
Steady interest

#2,094 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 Yerba Mate

What is Yerba Mate?

Yerba Mate
  • Energy and alertness
  • Weight loss
  • Mental focus
  • Digestive support
  • Antioxidant support

Yerba mate is a caffeine-containing herbal beverage from South America that is widely enjoyed for its stimulating, coffee-like effects. While it is rich in antioxidants and is being studied for weight, blood sugar, and cholesterol, strong human evidence for most health claims is limited. Drinking very hot mate over many years has been linked to higher risk of certain cancers, so enjoy it warm and in moderation.

Read the full Yerba Mate monograph & all interactions
Keep checking

Other Drugs & Yerba Mate

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

8Major
504Moderate
573Minor
1,744No known interaction
8 Major 504 Moderate 573 Minor 1,744 No interaction
Major

8 interactions

Moderate

504 interactions

Showing 60 of 504 moderate interactions — see all 504 on the Yerba Mate page.

Minor

573 interactions

Showing 60 of 573 minor interactions — see all 573 on the Yerba Mate page.

No interaction 1,744 drugs checked — show the list

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

Showing the 60 most looked-up of 1,744 medications checked with no known interaction — see the full Yerba Mate list.

See the full Yerba Mate 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
Yerba Mate 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 Yerba Mate and pioglitazone, metformin Together: Common Questions

Can you take Yerba Mate 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 4 interactions listed for Yerba Mate and pioglitazone, metformin?
pioglitazone, metformin belongs to more than one drug category, and Yerba Mate 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 Yerba Mate 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.