Drug & supplement interaction

Berberine + Glipizide, Metformin

Glipizide, Metformin brand name: Metaglip.

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

Glipizide, Metformin falls into 3 drug categories that Berberine can interact with; the most serious is rated moderate. Theoretically, berberine might increase serum levels of drugs metabolized by CYP2C9.

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

Berberine and Glipizide, Metformin

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

Why Are There 3 Interactions?

Berberine interacts with whole categories of medication. Glipizide, Metformin falls into 3 of those categories, so it can interact with Berberine 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 2C9 (CYP2C9) SUBSTRATES

1 of 3

Why this applies to Glipizide, Metformin

Glipizide, Metformin falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Berberine interacts with.

Theoretically, berberine might increase serum levels of drugs metabolized by CYP2C9.
Preliminary clinical research shows that berberine can inhibit CYP2C9. Theoretically, taking berberine with drugs metabolized by CYP2C9 might increase drug levels and increase the risk of adverse effects.
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 thing to keep an eye on with Metaglip (which combines glipizide and metformin). The glipizide part is cleared by a liver enzyme called CYP2C9, and early research suggests berberine may slow that enzyme down. If glipizide gets cleared more slowly, it can build up in your body and push your blood sugar lower than intended. That raises the odds of low blood sugar (hypoglycemia), which can show up as shakiness, sweating, dizziness, confusion, or feeling weak. Berberine on its own can also nudge blood sugar down, so the two together may add up.

This is mostly theoretical and based on lower-quality studies, so don't panic. But please loop in your pharmacist or doctor before combining them, and watch your sugars more closely if you do.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
Moderate

ANTIDIABETES DRUGS

2 of 3

Glipizide, Metformin also falls under ANTIDIABETES DRUGS.

Theoretically, berberine may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Clinical research shows that berberine may lower blood glucose levels. Theoretically, berberine might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.
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 thing to keep in mind: Metaglip already combines two blood sugar lowering medicines (glipizide and metformin). Berberine, on its own, also tends to nudge blood sugar down. So the worry isn't about your liver breaking anything down differently, it's simply that you could be stacking two sugar-lowering effects on top of each other. That extra push can drop your blood sugar too low.

With glipizide in the mix, watch for signs like shakiness, sweating, dizziness, a racing heart, or feeling confused or unusually hungry. Honestly, this is a theoretical concern based on how these work, not something proven in big studies, so don't panic. Just talk with your pharmacist or doctor before adding berberine, and check your sugars a bit more closely if you do.

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
  5. Blais JE, Huang X, Zhao JV. Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Drugs 2023;83(5):403-427. PubMed
Moderate

METFORMIN (Glucophage)

3 of 3
Theoretically, berberine might increase the therapeutic and adverse effects of metformin.
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.
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 thing to keep in mind with your Metaglip, which is a combo of glipizide and metformin. Berberine is a supplement that also tends to lower blood sugar on its own, so stacking it on top of two blood-sugar drugs can push your levels lower than you want. On top of that, lab and animal studies suggest berberine may slow how your body clears the metformin part, letting more of it build up. That could mean more of metformin's usual effects, including stomach upset, nausea, and diarrhea.

I want to be honest that this is mostly theoretical right now, based on test-tube and animal data, not strong human studies. Interestingly, the timing seemed to matter most when berberine was taken about 2 hours before metformin. Please don't change anything on your own. Just loop in your pharmacist or doctor first, and watch for shaky, sweaty low-sugar symptoms if you do combine 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

Berberine Also Interacts With Other Medications

Berberine has 1 major, 1,158 moderate known drug interactions in our database — the Glipizide, Metformin one above is among them. If you take anything else, check it against the full list below.

Major 1 Moderate 1,158 No known interaction 1,671 (incl. Glipizide, Metformin)
Taking anything else?

Check Another of Your Medications Against Berberine

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

From our Q&A

Questions About Berberine or Glipizide, Metformin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Berberine or Glipizide, Metformin, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Glipizide, Metformin

This page covers Berberine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Glipizide, Metformin page lists 307 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Siberian Cocklebur (major), Acai (moderate), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 2 major · 257 moderate · 48 minor.

From our pharmacist’s overview on the Glipizide, Metformin page

“Glipizide and metformin (Metaglip) already work hard to pull blood sugar down, which is exactly why this list of 307 ingredients deserves genuine vigilance rather than a shrug. Most of them, 239, can lower glucose on their own, and stacked on this pill the combined effect can tip into true hypoglycemia.”

Reviewed by 2 · Jul 18, 2026

Open the Glipizide, Metformin interaction page

One more smart check

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

We hold 908 real supplement products containing Berberine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Berberine. Your product may carry other ingredients that interact with Glipizide, Metformin too, on top of Berberine — 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 Berberine and Glipizide, 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 Berberine
Top 10%

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

29 days ago today
Medication Glipizide, Metformin
Steady interest

#1,550 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 Berberine

What is Berberine?

Berberine
  • Blood sugar control
  • High cholesterol
  • Heart and metabolic health
  • Digestive upset
  • Antimicrobial support
  • Weight management

Berberine is a yellow plant compound that has shown promise for lowering blood sugar and cholesterol in some studies, but the quality of research varies and it is not a replacement for prescribed medicine. It can cause stomach upset and should be avoided during pregnancy and breastfeeding. Always check with your pharmacist or doctor before starting it, especially if you take other medications.

Read the full Berberine monograph & all interactions
Keep checking

Other Drugs & Berberine

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

1Major
1,158Moderate
0Minor
1,670No known interaction
1 Major 1,158 Moderate 1,670 No interaction
Major

1 interaction

Moderate

1,158 interactions

Showing 60 of 1,158 moderate interactions — see all 1,158 on the Berberine page.

No interaction 1,670 drugs checked — show the list

We also checked Berberine 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 Berberine list.

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

Can you take Berberine with Glipizide, 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 Berberine and Glipizide, Metformin?
Glipizide, Metformin belongs to more than one drug category, and Berberine 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 Berberine and Glipizide, 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 Glipizide, Metformin and Berberine?

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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.