Drug & supplement interaction

Goldenseal + pioglitazone, metformin

pioglitazone, metformin brand name: ActoPlus Met.

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

pioglitazone, metformin falls into 3 drug categories that Goldenseal can interact with; the most serious is rated moderate. Goldenseal might increase serum levels of drugs metabolized by CYP3A4.

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

Goldenseal and pioglitazone, metformin

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

Why Are There 3 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

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Why this applies to pioglitazone, metformin

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

Goldenseal might increase serum levels of drugs metabolized by CYP3A4.
Most clinical and in vitro research shows that goldenseal inhibits CYP3A4 enzyme activity and increases serum levels of CYP3A4 substrates, such as midazolam. However, in one small clinical study, goldenseal did not affect the levels of indinavir, a CYP3A4 substrate, in healthy volunteers. This is likely due to the fact that indinavir has a high oral bioavailability, making it an inadequate probe for CYP3A4 interactions and/or that it is primarily metabolized by hepatic CYP3A, while goldenseal has more potential to inhibit intestinal CYP3A enzyme activity. Both goldenseal extract and its isolated constituents berberine and hydrastine inhibit CYP3A, with hydrastine possibly having more inhibitory potential than berberine.
Severity Moderate Likelihood Possible Evidence B

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 key thing with this combo product: only the pioglitazone half is touched by goldenseal. Pioglitazone is partly broken down by a liver enzyme called CYP3A4, and goldenseal tends to slow that enzyme down. That can let pioglitazone build up a bit more than usual, which may nudge its effects (and side effects) up. With pioglitazone that can mean things like fluid retention, swelling in the legs, weight gain, or low blood sugar when it's paired with metformin.

The metformin part isn't processed this way, so it's largely along for the ride. This is based on modest human evidence, so it's worth a real conversation. Don't change anything on your own. Just check with your pharmacist or doctor and watch your blood sugar and any new swelling.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  2. Sandhu RS, Prescilla RP, Simonelli TM, Edwards DJ. Influence of goldenseal root on the pharmacokinetics of indinavir. J Clin Pharmacol 2003;43:1283-8.. PubMed
  3. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  4. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
  5. Gurley BJ, et al. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activitiy In Vivo. Clin Pharmacol Ther. 2008;83(1):61-69.
  6. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  7. Nguyen JT, Tian DD, Tanna RS, et al. An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Ob
Moderate

ANTIDIABETES DRUGS

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pioglitazone, metformin also falls under ANTIDIABETES DRUGS.

Theoretically, goldenseal might increase the risk of hypoglycemia when used with antidiabetes drugs.
Goldenseal contains berberine. Clinical research shows that berberine can lower blood glucose levels. However, this effect has not been reported with goldenseal.
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. Your ActoPlus Met combines pioglitazone and metformin, both of which work to bring your blood sugar down. Goldenseal contains a compound called berberine, and in studies berberine on its own can also nudge blood sugar lower. So in theory, stacking the two could push your numbers down a little too far.

I want to be honest about how soft this is. This warning is theoretical, based on how berberine behaves, and the blood-sugar-lowering effect has not actually been reported with goldenseal itself. Still, if you do take both, watch for shakiness, sweating, dizziness, or feeling lightheaded. Keep an eye on your readings and check with your pharmacist or doctor before adding goldenseal.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008;93:2559-65. PubMed
  2. Yin, J., Xing, H., and Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008;57(5):712-717. PubMed
  3. Zhang, H., Wei, J., Xue, R., Wu, J. D., Zhao, W., Wang, Z. Z., Wang, S. K., Zhou, Z. X., Song, D. Q., Wang, Y. M., Pan, H. N., Kong, W. J., and Jiang, J. D. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin re
  4. Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H., Ma, Y., Zhang, Y., Zhang, H., and Guan, Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndro
Moderate

METFORMIN (Glucophage)

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Theoretically, goldenseal might reduce blood levels of metformin.
In vitro research shows that goldenseal extract decreases the bioavailability of metformin, likely by interfering with transport, intestinal permeability, or other processes involved in metformin absorption. It is unclear which, if any, of metformin's transporters are inhibited by goldenseal. Goldenseal does not appear to alter the clearance or half-life of metformin.
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 possible concern here is really with the metformin part. Lab studies (done in test tubes and cells, not in people) suggest goldenseal might lower how much metformin your gut actually absorbs. If less metformin gets in, it could work a little less well, meaning your blood sugar might run higher than expected.

I want to be honest about the strength of this: the evidence is very preliminary and theoretical, so it's hard to say how much it would matter in real life. The pioglitazone side isn't expected to be affected. If you'd like to try goldenseal, check with your pharmacist or doctor first, and keep an eye on your blood sugar readings.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Nguyen JT, Tian DD, Tanna RS, et al. Assessing transporter-mediated natural product-drug interactions via in vitro-in vivo extrapolation: clinical evaluation with a probe cocktail. Clin Pharmacol Ther 2021;109(5):1342-52.

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

Goldenseal Also Interacts With Other Medications

Goldenseal has 1,235 moderate, 1 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 1,235 Minor 1 No known interaction 1,594 (incl. pioglitazone, metformin)
Taking anything else?

Check Another of Your Medications Against Goldenseal

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

Everything else you take

See Every Supplement That Interacts With pioglitazone, metformin

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

We hold 1,726 real supplement products containing Goldenseal, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Goldenseal. Your product may carry other ingredients that interact with pioglitazone, metformin too, on top of Goldenseal — 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 Goldenseal 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 Goldenseal
Top 10%

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

29 days ago today
Medication pioglitazone, metformin
Steady interest

#2,035 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 Goldenseal

What is Goldenseal?

Goldenseal
  • Digestive upset and diarrhea
  • Colds and respiratory infections
  • Sore throat and mouth sores
  • Skin and eye irritation (topical/traditional)
  • Antimicrobial support

Goldenseal is a popular North American herb that contains berberine, a compound studied for antimicrobial effects. However, strong human evidence for its many traditional uses is largely lacking, and it should be avoided during pregnancy and breastfeeding. Talk to a pharmacist or doctor before using it.

Read the full Goldenseal monograph & all interactions
Keep checking

Other Drugs & Goldenseal

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

0Major
1,235Moderate
1Minor
1,593No known interaction
1,235 Moderate 1 Minor 1,593 No interaction
Moderate

1,235 interactions

Showing 60 of 1,235 moderate interactions — see all 1,235 on the Goldenseal page.

Minor

1 interaction

No interaction 1,593 drugs checked — show the list

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

Showing the 60 most looked-up of 1,593 medications checked with no known interaction — see the full Goldenseal list.

See the full Goldenseal 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
Goldenseal 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 Goldenseal and pioglitazone, metformin Together: Common Questions

Can you take Goldenseal 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 Goldenseal and pioglitazone, metformin?
pioglitazone, metformin belongs to more than one drug category, and Goldenseal 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 Goldenseal 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.