Drug & supplement interaction

Ketogenic Diet + Tolbutamide

Tolbutamide brand name: Orinase.

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

Ketogenic Diet has a moderate interaction with Tolbutamide. Theoretically, following the ketogenic diet while using antidiabetes drugs might increase the risk of hypoglycemia.

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

Ketogenic Diet 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 Ketogenic Diet interacts with.

Theoretically, following the ketogenic diet while using antidiabetes drugs might increase the risk of hypoglycemia.
The ketogenic diet involves a very low intake of carbohydrates, which can result in decreased blood glucose levels in patients taking antidiabetes drugs. In some patients, the need for antidiabetes drugs is reduced. Hypoglycemia has also occurred in some individuals without diabetes, although this is uncommon.
Severity Moderate Likelihood Possible Evidence B

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 thing to keep an eye on if you're thinking about a keto diet while taking tolbutamide (Orinase). This medication pushes your pancreas to release more insulin, which lowers your blood sugar. A ketogenic diet already cuts way back on carbs, so on its own it tends to drop blood sugar too. Stack the two together and you may end up lower than you want, which is what we call hypoglycemia.

For you, that could show up as shakiness, sweating, dizziness, confusion, or feeling suddenly weak or irritable. This concern is reasonable but mostly theoretical, and folks respond differently. Please don't change your dose on your own. Check in with your doctor or pharmacist first, since they may want you to monitor your sugars more closely or adjust things safely.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Liu H, Yang Y, Wang Y, et al. Ketogenic diet for treatment of intractable epilepsy in adults: A meta-analysis of observational studies. Epilepsia Open. 2018;3(1):9-17. PubMed
  2. Yancy WS Jr, Westman EC, McDuffie JR, et al. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss. Arch Intern Med. 2010;170(2):136-45. PubMed
  3. Goday A, Bellido D, Sajoux I, et al. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr Diabetes. 2016;6(9):e230. PubMed
  4. Saslow LR, Mason AE, Kim S, et al. An online intervention comparing a very low-carbohydrate ketogenic diet and lifestyle recommendations versus a plate method diet in overweight individuals with type 2 diabetes: A randomized controlled trial. J Med Intern
  5. Hussain TA, Mathew TC, Dashti AA, Asfar S, Al-Zaid N, Dashti HM. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition. 2012;28(10):1016-21. PubMed
  6. Cervenka MC, Hocker S, Koenig M, et al. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology. 2017;88(10):938-943. 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

Ketogenic Diet Also Interacts With Other Medications

Ketogenic Diet has 136 moderate, 122 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 136 Minor 122 No known interaction 2,572 (incl. Tolbutamide)
Taking anything else?

Check Another of Your Medications Against Ketogenic Diet

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

Everything else you take

See Every Supplement That Interacts With Tolbutamide

This page covers Ketogenic Diet 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

How much people look this up

Where Ketogenic Diet 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 Ketogenic Diet
Steady interest

#1,027 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Tolbutamide
Steady interest

#1,849 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.

Eating pattern

About Ketogenic Diet

What is Ketogenic Diet?

  • Weight loss
  • Type 2 diabetes and blood sugar control
  • Drug-resistant epilepsy (especially in children)
  • Reducing appetite
  • Athletic and metabolic interest

The ketogenic diet is a very low-carbohydrate, high-fat eating plan that shifts the body to burn fat for fuel. It has the strongest evidence as a medical therapy for hard-to-treat epilepsy and may help short-term weight loss and blood sugar, but it can be hard to sustain and is not right for everyone. Talk with a doctor or pharmacist before starting, especially if you have a medical condition or take medication.

Read the full Ketogenic Diet 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 & Ketogenic Diet

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

0Major
136Moderate
122Minor
2,571No known interaction
136 Moderate 122 Minor 2,571 No interaction
Moderate

136 interactions

Showing 60 of 136 moderate interactions — see all 136 on the Ketogenic Diet page.

Minor

122 interactions

Showing 60 of 122 minor interactions — see all 122 on the Ketogenic Diet page.

No interaction 2,571 drugs checked — show the list

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

Showing the 60 most looked-up of 2,571 medications checked with no known interaction — see the full Ketogenic Diet list.

See the full Ketogenic Diet 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
Ketogenic Diet 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

Following Ketogenic Diet While Taking Tolbutamide: Common Questions

Can you follow Ketogenic Diet while taking 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 Ketogenic Diet 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 Ketogenic Diet?

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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.