Drug & supplement interaction

Bitter Orange + Metformin Hydrochloride

Metformin Hydrochloride brand name: Riomet ER.

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

Bitter Orange has a moderate interaction with Metformin Hydrochloride. Theoretically, bitter orange might increase the risk of hypoglycemia when taken with antidiabetes drugs.

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

Bitter Orange and Metformin Hydrochloride

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

Moderate

ANTIDIABETES DRUGS

Why this applies to Metformin Hydrochloride

Metformin Hydrochloride falls under ANTIDIABETES DRUGS — the group Bitter Orange interacts with.

Theoretically, bitter orange might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Some clinical research shows that drinking a tea containing bitter orange and Indian snakeroot reduces fasting and postprandial glucose levels in patients with type 2 diabetes who are using antidiabetes drugs. However, it is unclear if these effects are due to bitter orange, Indian snakeroot, or the combination. An animal study also shows that p-synephrine in combination with gliclazide , a sulfonylurea, causes an additional 20% to 44% decrease in glucose levels when compared with gliclazide alone.
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

If you're taking metformin to manage type 2 diabetes, here's the gist with bitter orange supplements: there's a chance the combination could push your blood sugar a little lower than metformin would on its own. Some small studies of bitter orange teas showed reduced fasting and after-meal glucose in people already on diabetes medicine, so the worry is added blood-sugar lowering, not less effect.

Honestly, the evidence here is thin and partly theoretical, and metformin by itself rarely causes serious lows. Still, it's worth watching for shakiness, sweating, dizziness, or confusion, especially if you also use insulin or a sulfonylurea. Bitter orange can also bump up heart rate and blood pressure. Please check with your pharmacist or doctor before adding it, and keep an eye on your readings.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Campbell-Tofte, J. I., Molgaard, P., Josefsen, K., Abdallah, Z., Hansen, S. H., Cornett, C., Mu, H., Richter, E. A., Petersen, H. W., Norregaard, J. C., and Winther, K. Randomized and double-blinded pilot clinical study of the safety and anti-diabetic ef
  2. Vatsavai LK, Kilari EK. Interaction of p-synephrine on the pharmacodynamic and pharmacokinetics of gliclazide in animal models. J Ayurveda Integr Med 2017; S0975-9476(16)30487-9. doi: 10.1016/j.jaim.2017.04.010.

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

Bitter Orange Also Interacts With Other Medications

Bitter Orange has 10 major, 875 moderate, 71 minor known drug interactions in our database — the Metformin Hydrochloride one above is one of them. If you take anything else, check it against the full list below.

Major 10 Moderate 875 Minor 71 No known interaction 1,874 (incl. Metformin Hydrochloride)
Taking anything else?

Check Another of Your Medications Against Bitter Orange

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

Everything else you take

See Every Supplement That Interacts With Metformin Hydrochloride

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Metformin Hydrochloride page lists 257 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 · 38 minor.

From our pharmacist’s overview on the Metformin Hydrochloride page

“Anyone taking metformin hydrochloride (Riomet ER) should treat this list with genuine care, because two of its 257 entries are rated major. Siberian cocklebur has caused severe hypoglycemia in people and should not be combined with metformin at all, and activated charcoal can adsorb the drug in the gut so less reaches your blood.”

Reviewed by 2 · Jul 18, 2026

Open the Metformin Hydrochloride interaction page

One more smart check

Taking Bitter Orange as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,000 real supplement products containing Bitter Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bitter Orange. Your product may carry other ingredients that interact with Metformin Hydrochloride too, on top of Bitter Orange — 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 Bitter Orange and Metformin Hydrochloride 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 Bitter Orange
Top 25%

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

29 days ago today
Medication Metformin Hydrochloride
Top 10%

#267 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 Bitter Orange

What is Bitter Orange?

Bitter Orange
  • Weight loss
  • Athletic performance and energy
  • Digestive upset
  • Appetite control
  • Aromatherapy for stress (neroli oil)

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance is limited, and because it can raise heart rate and blood pressure, people with heart problems, high blood pressure, or who are pregnant should avoid it. Talk to your pharmacist or doctor before using it, especially if you take other stimulants.

Read the full Bitter Orange monograph & all interactions
Keep checking

Other Drugs & Bitter Orange

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

10Major
875Moderate
71Minor
1,873No known interaction
10 Major 875 Moderate 71 Minor 1,873 No interaction
Major

10 interactions

Moderate

875 interactions

Showing 60 of 875 moderate interactions — see all 875 on the Bitter Orange page.

Minor

71 interactions

Showing 60 of 71 minor interactions — see all 71 on the Bitter Orange page.

No interaction 1,873 drugs checked — show the list

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

Showing the 60 most looked-up of 1,873 medications checked with no known interaction — see the full Bitter Orange list.

See the full Bitter Orange interactions page
See every supplement checked against Metformin Hydrochloride, 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
Bitter Orange monograph › Uses, safety, and every drug interaction in one place Metformin Hydrochloride supplement interactions › Every supplement checked against Metformin Hydrochloride, ranked by severity 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 Bitter Orange and Metformin Hydrochloride Together: Common Questions

Can you take Bitter Orange with Metformin Hydrochloride?
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 Bitter Orange and Metformin Hydrochloride 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 Hydrochloride and Bitter Orange?

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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.