Drug & supplement interaction

Bitter Orange + Insulin Lispro Recombinant

Insulin Lispro Recombinant brand name: Humalog Kwikpen.

Moderate Interaction
The bottom line Moderate

Bitter Orange has a moderate interaction with Insulin Lispro Recombinant. 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 Insulin Lispro Recombinant

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

Moderate

ANTIDIABETES DRUGS

Why this applies to Insulin Lispro Recombinant

Insulin Lispro Recombinant 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

Here's the gist for Humalog (insulin lispro). Insulin lispro is a fast-acting mealtime insulin that lowers your blood sugar directly, so it isn't activated by an enzyme the way some pills are. The concern with bitter orange is that it may add a little extra blood-sugar-lowering on top of your insulin, which could nudge you toward low blood sugar (hypoglycemia).

That means more chances of shakiness, sweating, a racing heart, confusion, or feeling lightheaded. Honestly, the evidence here is thin and partly theoretical, often mixed with another herb, so I wouldn't panic. Still, bitter orange is a stimulant that can raise heart rate and blood pressure, which isn't ideal in diabetes. Please check with your pharmacist or doctor before adding it, and keep monitoring your sugars.

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 Insulin Lispro Recombinant one above is one of them. If you take anything else, check it against the full list below.

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 Insulin Lispro Recombinant

This page covers Bitter Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Insulin Lispro Recombinant page lists 242 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Chelation Therapy Products (major), Siberian Cocklebur (major), Acai (moderate), African Wild Potato (moderate) and Agaricus Mushroom (moderate).

By severity: 2 major · 211 moderate · 29 minor.

From our pharmacist’s overview on the Insulin Lispro Recombinant page

“Two of the 242 entries here rate major, and they are the place to start. Siberian cocklebur has caused severe hypoglycemia, and chelation products containing EDTA can drop blood glucose steeply while also interfering with the insulin itself, so neither belongs anywhere near insulin lispro (Humalog KwikPen).”

Reviewed by 2 · Jul 18, 2026

Open the Insulin Lispro Recombinant 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 Insulin Lispro Recombinant 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 Insulin Lispro Recombinant 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 Insulin Lispro Recombinant
Steady interest

#2,223 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
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
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

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Pharmacist Counseling Corner

Taking Bitter Orange and Insulin Lispro Recombinant Together: Common Questions

Can you take Bitter Orange with Insulin Lispro Recombinant?
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 Insulin Lispro Recombinant 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

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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.