Drug & supplement interaction

Neem + Tolbutamide

Tolbutamide brand name: Orinase.

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

Tolbutamide falls into 2 drug categories that Neem can interact with; the most serious is rated moderate. Neem might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Neem and Tolbutamide

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Neem interacts with whole categories of medication. Tolbutamide falls into 2 of those categories, so it can interact with Neem in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ANTIDIABETES DRUGS

1 of 2

Why this applies to Tolbutamide

Tolbutamide falls under ANTIDIABETES DRUGS — the group Neem interacts with.

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 thing to keep an eye on: Tolbutamide already lowers your blood sugar, and neem may nudge it down even further. Neem has shown some blood-sugar-lowering activity of its own, so stacking the two could push you too low. That's called hypoglycemia, and with a sulfonylurea like tolbutamide it can show up as shakiness, sweating, dizziness, a racing heart, confusion, or feeling suddenly very hungry.

To be fair, much of this is based on lab and early human studies rather than strong proof, so it's a possible concern, not a guaranteed one. Still, I wouldn't add neem supplements on your own. Check in with your pharmacist or doctor first, and if you do use both, watch your glucose readings a little more closely.

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 2C9 (CYP2C9) SUBSTRATES

2 of 2

Tolbutamide also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP2C9 substrates.
In vitro research shows that neem leaf methanol extract inhibits CYP2C9 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 basic idea with neem and your tolbutamide (Orinase). Your body uses a liver enzyme called CYP2C9 to clear tolbutamide out of your system. In test-tube studies, neem leaf extract seems to slow that enzyme down. If that happened in a real person, tolbutamide could linger longer and hit harder than expected, which for a diabetes pill like this mainly means a bigger risk of low blood sugar (shakiness, sweating, dizziness, confusion, or feeling faint).

The honest part: this is only a lab finding, and it hasn't actually been seen in people, so I wouldn't panic. Still, since low blood sugar is no joke, check with your pharmacist or doctor before adding neem, and watch your readings a bit more closely if you do.

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 Tolbutamide 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. Tolbutamide)
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 Tolbutamide

This page covers Neem only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tolbutamide page lists 305 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 · 255 moderate · 48 minor.

From our pharmacist’s overview on the Tolbutamide page

“People take tolbutamide (Orinase) to lower blood sugar in type 2 diabetes, and diabetes is exactly the condition supplement shelves target, which is why this list runs to 305 ingredients and deserves real caution. Of those, 239 also push glucose around, most often downward, so combining them can drive sugar lower than intended.”

Reviewed by 2 · Jul 18, 2026

Open the Tolbutamide 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 Tolbutamide 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 Tolbutamide 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 half

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

29 days ago today
Medication Tolbutamide
Steady interest

#2,180 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
Medication

About Tolbutamide

What Is Tolbutamide Used For?

Brand name: Orinase

  • Tolbutamide is used along with diet and exercise, and sometimes with other medications, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Tolbutamide is in a class of medications called sulfonylureas. Tolbutamide lowers blood sugar by causing the pancreas to produce insulin (a natural substance that is needed to break down sugar in the body) and helping the body use insulin efficiently. This medication will only help lower blood sugar in people whose bodies produce insulin naturally. Tolbutamide is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may occur if high blood sugar is not treated).

  • Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.

See full Tolbutamide drug information
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 Tolbutamide, 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 Tolbutamide supplement interactions › Every supplement checked against Tolbutamide, ranked by severity Tolbutamide drug information › The full plain-English guide to this medication 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 Tolbutamide Together: Common Questions

Can you take Neem with Tolbutamide?
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 2 interactions listed for Neem and Tolbutamide?
Tolbutamide 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 Tolbutamide 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.