Drug & supplement interaction

Neem + 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 Neem can interact with; the most serious is rated moderate. Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Neem and pioglitazone, metformin

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

Why Are There 3 Interactions?

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

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that neem leaf methanol extract inhibits CYP3A4 enzymes. So far, this reaction has not been reported in humans.
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 for your ActoPlus Met, which combines pioglitazone and metformin. Lab studies suggest neem leaf extract may slow down a liver enzyme called CYP3A4. Pioglitazone is partly cleared by that enzyme, so in theory neem could let it build up a bit. Neither of these is a prodrug, so we're talking about a slightly stronger effect, not a weaker one.

If pioglitazone levels crept up, you might see more of its usual effects, like fluid retention, swelling in the legs, weight gain, or a low blood sugar dip (more so when paired with other diabetes meds). Honestly though, this is only a test-tube finding and hasn't been seen in real people. Metformin isn't affected by this pathway. Just give your pharmacist a heads-up before starting neem.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Amaeze O, Eng H, Horlbogen L, Varma MVS, Slitt A. Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria. Eur J Drug Metab Pharmacokinet. 2021;46(3):437-450. PubMed
Moderate

ANTIDIABETES DRUGS

2 of 3

pioglitazone, metformin also falls under ANTIDIABETES DRUGS.

Neem might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Some clinical research shows that neem can lower blood glucose levels in adults with type 2 diabetes, including those already taking 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 simple version: both pioglitazone and metformin work to lower your blood sugar, and neem appears to nudge blood sugar down too. Stack them together and the effects can add up, which means your sugar could drop lower than you want. That can leave you feeling shaky, sweaty, dizzy, irritable, or unusually tired. With this combo pill, it's worth paying attention.

Now, the honesty part: most of this evidence comes from lab and animal work, with only a little human research, so it isn't a strong or certain interaction. Neither drug is a prodrug here, so we're really just talking about overlapping blood-sugar-lowering, not a metabolism problem. If you'd like to try neem, check your glucose more often at first and run it by your pharmacist or doctor before starting.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U. Biological activities and medicinal properties of neem (Azadirachta indica). Curr Sci 2002;82:1336-45.
  2. Pingali U, Ali MA, Gundagani S, Nutalapati C. Evaluation of the effect of an aqueous extract of Azadirachta indica (neem) leaves and twigs on glycemic control, endothelial dysfunction and systemic inflammation in subjects with type 2 diabetes mellitus - a
Moderate

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES

3 of 3

pioglitazone, metformin also falls under CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES.

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP2C8 substrates.
In vitro research shows that neem leaf methanol extract inhibits CYP2C8 enzymes. So far, this reaction has not been reported in humans.
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 for your ActoPlus Met, which combines pioglitazone and metformin. The pioglitazone half is cleared by a liver enzyme called CYP2C8. In test tube studies, neem leaf extract appears to slow that enzyme down. If that held true in people, pioglitazone could build up and act a little stronger, which might mean more fluid retention, swelling in the ankles, weight gain, or a greater chance of low blood sugar (especially if you take other diabetes meds). The metformin part isn't really handled by this enzyme, so it's the pioglitazone we'd watch.

The big caveat: this is only lab data and hasn't been seen in actual patients, so don't be alarmed. Still, run it by your pharmacist or doctor before adding a neem supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Amaeze O, Eng H, Horlbogen L, Varma MVS, Slitt A. Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria. Eur J Drug Metab Pharmacokinet. 2021;46(3):437-450. 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

Neem Also Interacts With Other Medications

Neem has 1,012 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 1,012 No known interaction 1,818 (incl. pioglitazone, metformin)
Taking anything else?

Check Another of Your Medications Against Neem

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

Everything else you take

See Every Supplement That Interacts With pioglitazone, metformin

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

We hold 288 real supplement products containing Neem, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Neem. Your product may carry other ingredients that interact with pioglitazone, metformin too, on top of Neem — 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 Neem 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 Neem
Top 25%

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

29 days ago today
Medication pioglitazone, metformin
Steady interest

#2,108 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 Neem

What is Neem?

Neem
  • Skin conditions
  • Dental and gum health
  • Antimicrobial and antiparasitic
  • Digestive upset
  • Blood sugar support
  • Insect repellent/pesticide

Neem is a tree from India used for centuries in traditional medicine, especially for skin, dental, and antimicrobial purposes. Some small studies are promising for oral health and skin, but high-quality human evidence is limited for most uses. Neem oil and seed extracts can be toxic if swallowed, especially in children, so use with caution and talk to your pharmacist or doctor first.

Read the full Neem monograph & all interactions
Keep checking

Other Drugs & Neem

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

0Major
1,012Moderate
0Minor
1,817No known interaction
1,012 Moderate 1,817 No interaction
Moderate

1,012 interactions

Showing 60 of 1,012 moderate interactions — see all 1,012 on the Neem page.

No interaction 1,817 drugs checked — show the list

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

Showing the 60 most looked-up of 1,817 medications checked with no known interaction — see the full Neem list.

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

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

Still Have a Question About pioglitazone, metformin and Neem?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.