Drug & supplement interaction

Papaya + Tolbutamide

Tolbutamide brand name: Orinase.

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

Papaya has a moderate interaction with Tolbutamide. Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects.

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

Papaya and Tolbutamide

Here is the interaction we found between these two, with the evidence behind it.

Moderate

ANTIDIABETES DRUGS

Why this applies to Tolbutamide

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

Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.
A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose.
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 simple version: tolbutamide (Orinase) already pushes your blood sugar down by telling your pancreas to release more insulin. A specific form of papaya, called fermented papaya, may nudge blood sugar lower too. Stack the two together and you could get an additive effect, meaning your sugar drops more than expected. In one small, low-quality study of folks on a related sulfonylurea, several people actually needed a lower medication dose while using fermented papaya.

What that looks like for you is low blood sugar: shakiness, sweating, dizziness, hunger, or feeling foggy. Note that this was seen with a concentrated fermented papaya supplement, not a slice of papaya at breakfast, and we don't know if regular papaya behaves the same way. Don't change anything on your own. Just loop in your pharmacist or doctor before starting a papaya supplement so they can keep an eye on your numbers.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Danese, C., Esposito, D., D'Alfonso, V., Cirene, M., Ambrosino, M., and Colotto, M. Plasma glucose level decreases as collateral effect of fermented papaya preparation use. Clin Ter. 2006;157(3):195-198.

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

Papaya Also Interacts With Other Medications

Papaya has 91 moderate known drug interactions in our database — the Tolbutamide one above is one of them. If you take anything else, check it against the full list below.

Moderate 91 No known interaction 2,739 (incl. Tolbutamide)
Taking anything else?

Check Another of Your Medications Against Papaya

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

Everything else you take

See Every Supplement That Interacts With Tolbutamide

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

We hold 1,801 real supplement products containing Papaya, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Papaya. Your product may carry other ingredients that interact with Tolbutamide too, on top of Papaya — 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 Papaya 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 Papaya
Top 25%

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

29 days ago today
Medication Tolbutamide
Steady interest

#1,619 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 Papaya

What is Papaya?

Papaya
  • Digestive upset and indigestion
  • Constipation
  • Wound and skin care (topical)
  • Intestinal parasites (traditional)
  • Supporting platelet counts in dengue (investigational)

Papaya is a tropical fruit that is nutritious and generally safe to eat as food, and it contains an enzyme called papain used as a digestive aid and meat tenderizer. Papaya leaf extract is being studied for raising platelet counts in dengue fever, but most other supplement uses have limited human evidence. Talk to your pharmacist or doctor before using concentrated papaya supplements, and avoid unripe (green) papaya and papaya seed products in pregnancy.

Read the full Papaya 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 & Papaya

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

0Major
91Moderate
0Minor
2,738No known interaction
91 Moderate 2,738 No interaction
Moderate

91 interactions

Showing 60 of 91 moderate interactions — see all 91 on the Papaya page.

No interaction 2,738 drugs checked — show the list

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

Showing the 60 most looked-up of 2,738 medications checked with no known interaction — see the full Papaya list.

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

Can you take Papaya 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.
How serious is the Papaya 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 Papaya?

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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.