Drug & supplement interaction

Soy + Tolbutamide

Tolbutamide brand name: Orinase.

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

Tolbutamide falls into 2 drug categories that Soy can interact with; the most serious is rated moderate. Soy can lower blood glucose and have additive effects with antidiabetes drugs.

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

Soy and Tolbutamide

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

Why Are There 2 Interactions?

Soy interacts with whole categories of medication. Tolbutamide falls into 2 of those categories, so it can interact with Soy 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 Soy interacts with.

Soy can lower blood glucose and have additive effects with antidiabetes drugs.
Clinical research shows that whole soy diets and soy-based meals reduce fasting glucose levels in diabetic and non-diabetic individuals. Also, individuals following a soy-based meal replacement plan seem to require lower doses of sulfonylureas and metformin to manage blood glucose levels when compared with individuals following a diet plan recommended by the American Diabetes Association.
Severity Moderate Likelihood Possible Evidence A

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: tolbutamide (Orinase) and soy can both push your blood sugar in the same direction, downward. Tolbutamide works by nudging your pancreas to release more insulin, and research shows that soy-heavy diets and soy meal replacements tend to lower fasting blood sugar on their own. Stack the two and the effect can add up, so your numbers may dip lower than expected.

This isn't dangerous on its own, but it does mean you could see more low blood sugar symptoms like shakiness, sweating, dizziness, or feeling hungry and irritable. The studies behind this are solid, but everyday food amounts of soy usually matter less than a big switch to soy-based meals or concentrated supplements. If you're starting either, check your sugars more closely and talk with your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Li, Z., Hong, K., Saltsman, P., DeShields, S., Bellman, M., Thames, G., Liu, Y., Wang, H. J., Elashoff, R., and Heber, D. Long-term efficacy of soy-based meal replacements vs an individualized diet plan in obese type II DM patients: relative effects on w
  2. Post-Skagegard, M., Vessby, B., and Karlstrom, B. Glucose and insulin responses in healthy women after intake of composite meals containing cod-, milk-, and soy protein. Eur J Clin Nutr 2006;60(8):949-954. PubMed
  3. Azadbakht, L., Kimiagar, M., Mehrabi, Y., Esmaillzadeh, A., Padyab, M., Hu, F. B., and Willett, W. C. Soy inclusion in the diet improves features of the metabolic syndrome: a randomized crossover study in postmenopausal women. Am J Clin Nutr 2007;85(3):7 PubMed
  4. Liu, Z. M., Chen, Y. M., and Ho, S. C. Effects of soy intake on glycemic control: a meta-analysis of randomized controlled trials. Am.J.Clin.Nutr. 2011;93(5):1092-1101. PubMed
  5. Zhang XM, Zhang YB, Chi MH. Soy protein supplementation reduces clinical indices in type 2 diabetes and metabolic syndrome. Yonsei Med J. 2016;57(3):681-9. PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

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

Soy might modestly induce CYP2C9 enzymes. However, this effect does not seem to be clinically significant.
In vitro research suggests that an unhydrolyzed soy extract might induce CYP2C9. However, the significance of this interaction is likely minimal. In healthy females taking a specific extract of soy (Genistein Soy Complex, Source Naturals), blood levels of losartan, a CYP2C9 substrate, were not significantly affected.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

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

Here's the gist: your body relies on an enzyme called CYP2C9 to clear tolbutamide out of your system. Some lab studies hint that soy might speed that enzyme up a little. If that happened in real life, tolbutamide could be cleared a bit faster, which in theory might make it work slightly less well at keeping your blood sugar down.

But honestly, I wouldn't lose sleep over this one. This concern comes from test-tube research, and when soy was actually studied in people with a similar CYP2C9 drug, blood levels barely budged. Everyday soy foods are very unlikely to cause a problem. If you take concentrated soy isoflavone supplements, just keep an eye on your blood sugar readings and mention it to your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang G, Xiao CQ, Li Z, et al. Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers. Ann Pharmacother 2009;43:1045-9. 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

Soy Also Interacts With Other Medications

Soy has 9 major, 342 moderate, 259 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.

Major 9 Moderate 342 Minor 259 No known interaction 2,220 (incl. Tolbutamide)
Taking anything else?

Check Another of Your Medications Against Soy

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

Everything else you take

See Every Supplement That Interacts With Tolbutamide

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

We hold 821 real supplement products containing Soy, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Soy. Your product may carry other ingredients that interact with Tolbutamide too, on top of Soy — 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 Soy 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 Soy
Top 25%

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

29 days ago today
Medication Tolbutamide
Steady interest

#2,116 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 Soy

What is Soy?

  • Menopause symptoms (hot flashes)
  • Heart and cholesterol health
  • Bone health
  • Plant-based protein source
  • General nutrition

Soy is a nutritious bean that is a staple food and a popular source of plant protein and isoflavones. Eating soy foods as part of a balanced diet is generally considered safe for most people, and there is moderate evidence it may modestly help cholesterol and some menopause symptoms, though results vary. Talk with your pharmacist or doctor before using concentrated soy isoflavone supplements, especially if you have a history of hormone-sensitive conditions.

Read the full Soy 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 & Soy

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

9Major
342Moderate
259Minor
2,219No known interaction
9 Major 342 Moderate 259 Minor 2,219 No interaction
Major

9 interactions

Moderate

342 interactions

Showing 60 of 342 moderate interactions — see all 342 on the Soy page.

Minor

259 interactions

Showing 60 of 259 minor interactions — see all 259 on the Soy page.

No interaction 2,219 drugs checked — show the list

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

Showing the 60 most looked-up of 2,219 medications checked with no known interaction — see the full Soy list.

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

Can you take Soy 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 Soy and Tolbutamide?
Tolbutamide belongs to more than one drug category, and Soy 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 Soy 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 Soy?

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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.