Drug & supplement interaction

Phellodendron + 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 Phellodendron can interact with; the most serious is rated moderate. Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP3A4.

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

Phellodendron and pioglitazone, metformin

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

Why Are There 3 Interactions?

Phellodendron interacts with whole categories of medication. pioglitazone, metformin falls into 3 of those categories, so it can interact with Phellodendron 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

1 of 3

Why this applies to pioglitazone, metformin

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

Theoretically, phellodendron might increase serum levels of drugs metabolized by CYP3A4.
Phellodendron contains berberine. In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, phellodendron might also inhibit CYP3A4.
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 ActoPlus Met: it combines two diabetes medicines. Your liver clears the pioglitazone part partly through an enzyme called CYP3A4. Phellodendron contains berberine, which may gently slow that same enzyme down. In theory, that could let pioglitazone build up a bit, which might mean stronger blood-sugar lowering or side effects like swelling (fluid retention), weight gain, or low blood sugar if combined with other factors. The metformin half isn't really processed this way, so it's the pioglitazone piece we'd watch.

Honestly, this is a theoretical concern based on lab and early human data, not strong proof. Still, since berberine itself can lower blood sugar, the bigger real-world worry may be your numbers dropping too low. Please check with your pharmacist or doctor before adding it.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  2. 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
  3. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  4. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
Moderate

ANTIDIABETES DRUGS

2 of 3

pioglitazone, metformin also falls under ANTIDIABETES DRUGS.

Theoretically, phellodendron may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Phellodendron contains berberine. Clinical research shows that berberine may lower blood glucose levels. Theoretically, phellodendron might also lower blood glucose levels.
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 already lowers blood sugar through two medicines, pioglitazone and metformin. Phellodendron contains berberine, and some studies suggest berberine can nudge blood sugar down on its own. So the worry is that stacking them could push your numbers a little too low. This is a theoretical concern based on how berberine behaves, not strong proof, so I don't want you to panic.

Still, it's worth watching. If you notice shakiness, sweating, dizziness, a fast heartbeat, or sudden hunger, those can be signs of low blood sugar (hypoglycemia). Please loop in your pharmacist or doctor before adding phellodendron, and keep checking your sugars closely if you do. Don't change your ActoPlus Met dose on your own.

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)

3 of 3
Theoretically, phellodendron might increase the therapeutic and adverse effects of metformin.
Phellodendron contains berberine. In vitro and animal studies show that berberine can increase the systemic exposure and half-life of metformin, potentially increasing metformin's effects and side effects. This interaction seems to be most apparent when berberine is administered 2 hours prior to metformin. Taking berberine and metformin at the same time does not appear to increase systemic exposure to metformin. It is unclear if phellodendron might have this same effect.
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 ActoPlus Met combines two diabetes medicines, and the part that matters here is the metformin. Phellodendron bark is rich in berberine, and in lab dishes and animal studies, berberine seems to slow how fast the body removes metformin. That means more metformin could hang around in your system, which could push your blood sugar lower and make the usual metformin side effects, like nausea, stomach upset, or diarrhea, more likely.

To be fair, this is a theoretical concern based mostly on berberine, not on Phellodendron itself, and it seemed strongest when berberine was taken about two hours before the dose. Still, since low blood sugar is no fun, please check with your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lyu Y, Zhang Y, Yang M, et al. Pharmacokinetic interactions between metformin and berberine in rats: Role of oral administration sequences and microbiota. Life Sci. 2019;235:116818. 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

Phellodendron Also Interacts With Other Medications

Phellodendron has 1,159 moderate 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 1,159 No known interaction 1,671 (incl. pioglitazone, metformin)
Taking anything else?

Check Another of Your Medications Against Phellodendron

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

Everything else you take

See Every Supplement That Interacts With pioglitazone, metformin

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

We hold 393 real supplement products containing Phellodendron, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Phellodendron. Your product may carry other ingredients that interact with pioglitazone, metformin too, on top of Phellodendron — 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 Phellodendron 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 Phellodendron
Top 25%

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

29 days ago today
Medication pioglitazone, metformin
Steady interest

#2,360 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 Phellodendron

What is Phellodendron?

Phellodendron
  • Digestive complaints and diarrhea
  • Inflammation and joint discomfort
  • Stress and weight management (in combination products)
  • Skin conditions (topical, traditional)
  • Antimicrobial support

Phellodendron is a traditional Chinese medicine bark (Huang Bai) that contains berberine and other plant compounds with antimicrobial and anti-inflammatory activity in lab studies. Human evidence for most uses is limited, and it is often sold in combination with other herbs, making its individual effects hard to judge. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Phellodendron monograph & all interactions
Keep checking

Other Drugs & Phellodendron

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

0Major
1,159Moderate
0Minor
1,670No known interaction
1,159 Moderate 1,670 No interaction
Moderate

1,159 interactions

Showing 60 of 1,159 moderate interactions — see all 1,159 on the Phellodendron page.

No interaction 1,670 drugs checked — show the list

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

Showing the 60 most looked-up of 1,670 medications checked with no known interaction — see the full Phellodendron list.

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

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