Drug & supplement interaction

Papaya + Metformin

Metformin brand names: Glucophage, Metformin.

Moderate Interaction
The bottom line Moderate

Papaya has a moderate interaction with Metformin. 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 Metformin

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

Moderate

ANTIDIABETES DRUGS

Why this applies to Metformin

Metformin 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 short version: papaya, especially the fermented kind taken as a concentrated supplement, may gently nudge your blood sugar lower on its own. When you stack that on top of metformin, the two can add up. The evidence here is modest, coming from one small, low-quality study that actually used a different diabetes drug, so think of this as a 'be aware' rather than a 'be alarmed.'

If your sugar drops too far, you might feel shaky, sweaty, lightheaded, or unusually hungry. Metformin by itself rarely causes lows, but adding a blood-sugar-lowering supplement could tip the balance. Eating papaya as fruit is unlikely to be a problem. If you're thinking about a fermented papaya supplement, check with your pharmacist or doctor first and keep an eye on your readings.

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 Metformin one above is one of them. If you take anything else, check it against the full list below.

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.

From our Q&A

Questions About Papaya or 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 Papaya or 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 Metformin

This page covers Papaya only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Metformin page lists 258 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), African Wild Potato (moderate) and Agaricus Mushroom (moderate).

By severity: 2 major · 217 moderate · 39 minor.

From our pharmacist’s overview on the Metformin page

“Siberian cocklebur is the ingredient I most want anyone taking metformin (Glucophage) to know about. It has caused severe low blood sugar in people, documented in humans, and it should not be combined with any glucose-lowering medication.”

Reviewed by 2 · Jul 18, 2026

Open the Metformin 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 Metformin 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 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 Papaya
Top 25%

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

29 days ago today
Medication Metformin
Top 1%

#29 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 Metformin

What Is Metformin Used For?

Brand names: Glucophage, Metformin

Metformin is used to improve blood sugar (glucose) control in people with type 2 diabetes mellitus. It is always used together with diet and exercise, not instead of them.

Metformin hydrochloride tablets and oral solution are approved for adults and children 10 years and older. Metformin hydrochloride extended-release tablets — including brands such as Fortamet, Glumetza, and Metformin Hydrochloride Extended Release — are approved for adults only.

See full Metformin 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
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
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

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Pharmacist Counseling Corner

Taking Papaya and Metformin Together: Common Questions

Can you take Papaya with 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.
How serious is the Papaya and 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 Metformin 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.