Drug & supplement interaction

Glucosamine + Tolbutamide

Tolbutamide brand name: Orinase.

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

Glucosamine has a minor interaction with Tolbutamide. Despite initial concerns, it is unlikely that glucosamine will interfere with the effects of antidiabetes drugs.

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

Glucosamine and Tolbutamide

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

Minor

ANTIDIABETES DRUGS

Why this applies to Tolbutamide

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

Despite initial concerns, it is unlikely that glucosamine will interfere with the effects of antidiabetes drugs.
In vitro and animal research has suggested that glucosamine might increase insulin resistance or decrease insulin production. This has raised concerns that taking glucosamine might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that glucosamine does not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, or type 2 diabetes patients.
Severity Minor Likelihood Unlikely Evidence B

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 good news if you take tolbutamide (Orinase) for your type 2 diabetes and want to try glucosamine for sore joints. Early lab and animal studies hinted that glucosamine might raise insulin resistance or lower insulin output, which could theoretically work against your diabetes medicine. But when researchers actually studied this in people, including folks with type 2 diabetes, glucosamine did not meaningfully budge blood sugar or HbA1c. So the worry mostly fizzled out.

In plain terms, glucosamine is unlikely to make your tolbutamide work less well or push your sugars around. Still, since tolbutamide can cause low blood sugar on its own, it's smart to keep checking your readings when you start anything new. Have a quick chat with your pharmacist or doctor first, especially if you also have a shellfish allergy.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Balkan B, Dunning BE. Glucosamine inhibits glucokinase in vitro and produces a glucose-specific impairment of in vivo insulin secretion in rats. Diabetes 1994;43:1173-9. PubMed
  2. Giaccari A, Morviducci L, Zorretta D, et al. In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia. Diabetologia 1995;38:518-24. PubMed
  3. Shankar RR, Zhu JS, Baron AD. Glucosamine infusion in rats mimics the beta-cell dysfunction of non-insulin-dependent diabetes mellitus. Metabolism 1998;47:573-7.
  4. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulfate on osteoarthritis progression: a randomised, placebo-controlled trial. Lancet 2001;357:251-6.
  5. Does glucosamine increase serum lipid levels and blood pressure? Pharmacist's Letter/Prescriber's Letter 2001;17(11):171115.
  6. Pavelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: A 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002;162:2113-23. PubMed
  7. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Arch Intern Med 2003; PubMed
  8. Yu JG, Boies SM, Olefsky JM. The effect of oral glucosamine sulfate on insulin sensitivity in human subjects. Diabetes Care 2003;26:1941-2. PubMed
  9. Muniyappa R, Karne RJ, Hall G, et al. Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects. Diabetes 2006;55:3142-50. PubMed
  10. Baron AD, Zhu JS, Zhu JH, et al. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity. J Clin Invest 1995;96(6):2792-801. PubMed
  11. Nelson BA, Robinson KA, Buse MG. High glucose and glucosamine induce insulin resistance via different mechanisms in 3T3-L1 adipocytes. Diabetes 2000;49(6):981-91. 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

Glucosamine Also Interacts With Other Medications

Glucosamine has 2 major, 13 moderate, 154 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.

Major 2 Moderate 13 Minor 154 No known interaction 2,661 (incl. Tolbutamide)
Taking anything else?

Check Another of Your Medications Against Glucosamine

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

From our Q&A

Questions About Glucosamine 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 Glucosamine 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 Glucosamine 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 Glucosamine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,984 real supplement products containing Glucosamine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Glucosamine. Your product may carry other ingredients that interact with Tolbutamide too, on top of Glucosamine — 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 Glucosamine 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 Glucosamine
Top 10%

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

29 days ago today
Medication Tolbutamide
Steady interest

#1,648 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 Glucosamine

What is Glucosamine?

Glucosamine
  • Osteoarthritis
  • Joint pain and stiffness
  • Cartilage support
  • Knee and hip joint health

Glucosamine is a natural compound found in cartilage and joint fluid, and it is one of the most popular supplements for osteoarthritis, especially of the knee. The evidence is mixed, with some people getting modest relief while others get little to no benefit. It is generally well tolerated, but talk to your pharmacist or doctor before starting it, especially if you have a shellfish allergy or diabetes.

Read the full Glucosamine 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 & Glucosamine

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

2Major
13Moderate
154Minor
2,660No known interaction
2 Major 13 Moderate 154 Minor 2,660 No interaction
Major

2 interactions

Moderate

13 interactions

Minor

154 interactions

Showing 60 of 154 minor interactions — see all 154 on the Glucosamine page.

No interaction 2,660 drugs checked — show the list

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

Showing the 60 most looked-up of 2,660 medications checked with no known interaction — see the full Glucosamine list.

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

Can you take Glucosamine with Tolbutamide?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Glucosamine and Tolbutamide interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Tolbutamide and Glucosamine?

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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.