Drug & supplement interaction

L-arginine + Tolbutamide

Tolbutamide brand name: Orinase.

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

L-arginine has a moderate interaction with Tolbutamide. Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.

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

L-arginine 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 L-arginine interacts with.

Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.
Preliminary clinical research shows that L-arginine decreases blood glucose levels in patients with type 2 diabetes.
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 simple version: tolbutamide (Orinase) already pushes your blood sugar down by nudging your pancreas to release more insulin. Some early research suggests L-arginine can lower blood sugar a little on its own too. Stack the two together and the effects could add up, which means your sugar might dip lower than you expect.

If that happens, you could feel the classic signs of low blood sugar: shakiness, sweating, dizziness, a racing heart, or feeling foggy and irritable. To be clear, this is a theoretical concern based on how each works, not something proven to be dangerous. I wouldn't lose sleep over it, but it's worth a quick chat with your pharmacist or doctor, and keep an eye on your home glucose readings if you do combine them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lucotti, P., Setola, E., Monti, L. D., Galluccio, E., Costa, S., Sandoli, E. P., Fermo, I., Rabaiotti, G., Gatti, R., and Piatti, P. Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in
  2. Jovanovic, A., Gerrard, J., and Taylor, R. The second-meal phenomenon in type 2 diabetes. Diabetes Care 2009;32(7):1199-1201. PubMed
  3. Yousefi Rad E, Nazarian B, Saboori S, Falahi E, Hekmatdoost A. Effects of l-arginine supplementation on glycemic profile: Evidence from a systematic review and meta-analysis of clinical trials. J Integr Med. 2020;18(4):284-291. 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

L-arginine Also Interacts With Other Medications

L-arginine has 394 moderate, 8 minor 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 394 Minor 8 No known interaction 2,428 (incl. Tolbutamide)
Taking anything else?

Check Another of Your Medications Against L-arginine

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

From our Q&A

Questions About L-arginine or Tolbutamide

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers L-arginine or Tolbutamide, 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 Tolbutamide

This page covers L-arginine 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 L-arginine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 26 real supplement products containing L-arginine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides L-arginine. Your product may carry other ingredients that interact with Tolbutamide too, on top of L-arginine — 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 L-arginine 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 L-arginine
Steady interest

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

29 days ago today
Medication Tolbutamide
Steady interest

#1,727 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 L-arginine

What is L-arginine?

L-arginine
  • High blood pressure
  • Erectile dysfunction
  • Athletic performance
  • Chest pain (angina)
  • Improving blood flow

L-arginine is an amino acid that the body uses to make nitric oxide, a substance that helps blood vessels relax and widen. It is popularly used for blood pressure, erectile dysfunction, and exercise, but the evidence is mixed and stronger for some uses than others. It is generally well tolerated in healthy adults, but talk with a pharmacist or doctor before using it, especially if you have heart problems or take other medicines.

Read the full L-arginine 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 & L-arginine

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

0Major
394Moderate
8Minor
2,427No known interaction
394 Moderate 8 Minor 2,427 No interaction
Moderate

394 interactions

Showing 60 of 394 moderate interactions — see all 394 on the L-arginine page.

Minor

8 interactions

No interaction 2,427 drugs checked — show the list

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

Showing the 60 most looked-up of 2,427 medications checked with no known interaction — see the full L-arginine list.

See the full L-arginine 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
L-arginine 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 L-arginine and Tolbutamide Together: Common Questions

Can you take L-arginine 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 L-arginine 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 L-arginine?

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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.