Drug & supplement interaction

Gymnema + Tolbutamide

Tolbutamide brand name: Orinase.

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

Tolbutamide falls into 3 drug categories that Gymnema can interact with; the most serious is rated moderate. Theoretically, gymnema might increase or decrease levels of drugs metabolized by CYP2C9.

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

Gymnema and Tolbutamide

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

Why Are There 3 Interactions?

Gymnema interacts with whole categories of medication. Tolbutamide falls into 3 of those categories, so it can interact with Gymnema 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 Tolbutamide

Tolbutamide falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Gymnema interacts with.

Theoretically, gymnema might increase or decrease levels of drugs metabolized by CYP2C9.
Animal research shows that gymnema can induce the CYP2C9 enzyme. In one animal study, gymnema caused a 2.4-fold increase in the clearance of tolbutamide, a CYP2C9 substrate, in rats. In vitro research also shows that gymnema can inhibit CYP2C9.
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 tricky part with pairing gymnema and tolbutamide: both of them can lower your blood sugar, but they may also tug on the same liver enzyme (called CYP2C9) that clears tolbutamide from your body. The lab and animal signals point in opposite directions. In one rat study, gymnema sped up that enzyme and cleared tolbutamide faster, which could mean a weaker effect and higher blood sugar. In test-tube work, gymnema slowed the enzyme instead, which could let tolbutamide build up and push your sugar too low (shakiness, sweating, confusion).

The honest takeaway is that this is theoretical and based only on animal and lab data, not people, so don't panic. Still, since both can move your blood sugar, please check with your pharmacist or doctor and watch your readings before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Rammohan B, Samit K, Chinmoy D, et al. Human cytochrome P450 enzyme modulation by gymnema sylvestre: a predictive safety evaluation by LC-MS/MS. Pharmacogn Mag. 2016 Jul;12(Suppl 4):S389-S394.
  2. Vaghela M, Sahu N, Kharkar P, Pandita N. In vivo pharmacokinetic interaction by ethanolic extract of gymnema sylvestre with CYP2C9 (tolbutamide), CYP3A4 (amlodipine) and CYP1A2 (phenacetin) in rats. Chem Biol Interact. 2017 Dec 25;278:141-151. PubMed
  3. Vaghela M, Iyer K, Pandita N. In vitro inhibitory effect of gymnema sylvestre extracts and total gymnemic acids fraction on select cytochrome P450 activities in rat liver microsomes. Eur J Drug Metab Pharmacokinet. 2017 Oct 10. PubMed
Moderate

ANTIDIABETES DRUGS

2 of 3

Tolbutamide also falls under ANTIDIABETES DRUGS.

Theoretically, taking gymnema with antidiabetes drugs might increase the risk of hypoglycemia.
Gymnema reduces blood glucose levels in some human and animal research. In human studies, it has been shown to enhance the blood glucose lowering effects of hypoglycemic drugs. However, other research in adults with prediabetes or metabolic syndrome suggests that gymnema does not reduce fasting levels of blood glucose. Until more is known, monitor blood glucose levels closely.
Severity Moderate Likelihood Probable Evidence B

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing to keep in mind: both Gymnema and tolbutamide (Orinase) work to push your blood sugar down. Tolbutamide does it by prodding your pancreas to release more insulin, and Gymnema may add its own modest sugar-lowering effect on top. Stack the two together and you could end up too low, which is what we call hypoglycemia.

That can show up as shakiness, sweating, dizziness, confusion, a racing heart, or feeling suddenly hungry. The research here is mixed and partly theoretical, so it's not a sure thing, but it's worth respecting. If you'd like to try Gymnema, please loop in your pharmacist or doctor first and check your blood sugar more closely so nobody is caught off guard.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Shanmugasundaram ER, Rajeswari G, Baskaran K, et al. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 1990;30:281-94. PubMed
  2. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER. Antidiabetic effect of leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990;30:295-300.
  3. Kamble B, Gupta A, Moothedath I, Khatal L, Janrao S, Jadhav A, et al. Effects of Gymnema sylvestre extract on the pharmacokinetics and pharmacodynamics of glimepiride in streptozotocin induced diabetic rats. Chem Biol Interact. 2016;245:30-8. PubMed
  4. Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Biomed Res Int. 2014; 2014:830285.
  5. Fabio GD, Romanucci V, De Marco A, Zarrelli A. Triterpenoids from Gymnema sylvestre and their pharmacological activities. Molecules. 2014;19(8):10956-81. PubMed
  6. Zuniga LY, Gonzalez-Ortiz M, Martinez-Abundis E. Effect of gymnema sylvestre administration on metabolic syndrome, insulin sensitivity, and insulin secretion. J Med Food. 2017 Aug;20(8):750-54.
  7. Gaytán Martínez LA, Sánchez-Ruiz LA, Zuñiga LY, González-Ortiz M, Martínez-Abundis E. Effect of Gymnema sylvestre administration on glycemic control, insulin secretion, and insulin sensitivity in patients with impaired glucose tolerance. J Med Food. 2021;
Moderate

TOLBUTAMIDE (Orinase)

3 of 3
Theoretically, taking gymnema with tolbutamide might the decrease levels of tolbutamide.
Animal research shows that gymnema, administered orally for 7 days, increases the clearance of tolbutamide by 2.4-fold when compared to control.
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 tricky part with this pairing: both Gymnema and Tolbutamide (Orinase) work to lower your blood sugar, but they may tug in opposite directions when it comes to drug levels. In animal studies, Gymnema sped up how fast the body cleared Tolbutamide (about 2.4 times faster), which could leave less of the drug in your system. That might make Tolbutamide work less well, allowing your blood sugar to creep up higher than expected.

I want to be honest with you though: this is based only on animal research, not human studies, so it's more of a theoretical concern. Gymnema itself can also lower blood sugar on its own, so the bigger real-world worry is unpredictable swings. Please don't start or stop anything on your own. Just check with your pharmacist or doctor first, and keep an eye on your home glucose readings.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Vaghela M, Sahu N, Kharkar P, Pandita N. In vivo pharmacokinetic interaction by ethanolic extract of gymnema sylvestre with CYP2C9 (tolbutamide), CYP3A4 (amlodipine) and CYP1A2 (phenacetin) in rats. Chem Biol Interact. 2017 Dec 25;278:141-151. 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

Gymnema Also Interacts With Other Medications

Gymnema has 346 moderate, 504 minor 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 346 Minor 504 No known interaction 1,980 (incl. Tolbutamide)
Taking anything else?

Check Another of Your Medications Against Gymnema

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

Everything else you take

See Every Supplement That Interacts With Tolbutamide

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

We hold 1,084 real supplement products containing Gymnema, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Gymnema. Your product may carry other ingredients that interact with Tolbutamide too, on top of Gymnema — 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 Gymnema 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 Gymnema
Top 25%

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

29 days ago today
Medication Tolbutamide
Steady interest

#2,111 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 Gymnema

What is Gymnema?

Gymnema
  • Blood sugar support
  • Type 2 diabetes
  • Sugar cravings
  • Weight management
  • Cholesterol support

Gymnema is an Ayurvedic herb best known for possibly helping lower blood sugar and reducing the taste of sweetness on the tongue. Some early human studies are encouraging for blood sugar support, but the evidence is still limited and not strong enough to replace standard treatment. If you have diabetes or take other medicines, talk with your pharmacist or doctor before using it.

Read the full Gymnema 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 & Gymnema

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

0Major
346Moderate
504Minor
1,979No known interaction
346 Moderate 504 Minor 1,979 No interaction
Moderate

346 interactions

Showing 60 of 346 moderate interactions — see all 346 on the Gymnema page.

Minor

504 interactions

Showing 60 of 504 minor interactions — see all 504 on the Gymnema page.

No interaction 1,979 drugs checked — show the list

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

Showing the 60 most looked-up of 1,979 medications checked with no known interaction — see the full Gymnema list.

See the full Gymnema 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
Gymnema 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 Gymnema and Tolbutamide Together: Common Questions

Can you take Gymnema 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 3 interactions listed for Gymnema and Tolbutamide?
Tolbutamide belongs to more than one drug category, and Gymnema 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 Gymnema 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

Still Have a Question About Tolbutamide and Gymnema?

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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.