Drug & supplement interaction

Apple + Simvastatin, Sitagliptin

Simvastatin, Sitagliptin brand name: Juvisync.

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

Simvastatin, Sitagliptin falls into 2 drug categories that Apple can interact with; the most serious is rated major. Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.

Read the full interaction report
SeverityMajor
LikelihoodLikely
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Apple and Simvastatin, Sitagliptin

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Apple interacts with whole categories of medication. Simvastatin, Sitagliptin falls into 2 of those categories, so it can interact with Apple in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

1 of 2

Why this applies to Simvastatin, Sitagliptin

Simvastatin, Sitagliptin falls under ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) — the group Apple interacts with.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.
Research shows that consuming apple juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP. Fexofenadine, atenolol, and aliskiren are substrates of OATP. Clinical research shows that coadministration of apple juice decreases bioavailability of fexofenadine by up to 78%, aliskiren by 63%, and atenolol by up to 82%. These effects appear to increase with larger quantities of apple juice. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.
Severity Major Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the situation with Juvisync, which combines simvastatin (a cholesterol pill) and sitagliptin (a blood sugar medicine). Apple juice can briefly block a transporter called OATP that helps pull certain drugs into your body. When that gateway is slowed, less of the medicine gets absorbed, so you may end up with weaker effects. For simvastatin that could mean your cholesterol isn't lowered as well, and for sitagliptin your blood sugar control could slip a bit.

The good news is this is a short-lived effect tied mainly to drinking actual apple juice, not from eating a whole apple now and then. A simple fix many people use is spacing the juice and the pill by at least 4 hours. Before changing anything, check with your pharmacist or doctor so your treatment stays on track.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bailey DG, Dresser GK, Munoz C, et al. Reduction of fexofenadine bioavailability by fruit juices. Clin Pharmacol Ther 2001;69:P21.
  2. Greenblatt DJ. Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides. J Clin Pharmacol 2009;49:1403-7. PubMed
  3. Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol 2010;70:645-55. PubMed
  4. Kamath AV, Yao M, Zhang Y, Chong S. Effect of fruit juices on the oral bioavailability of fexofenadine in rats. J Pharm Sci 2005;94:233-9. PubMed
  5. Tapaninen T, Neuvonen PJ, Niemi M. Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren. Br J Clin Pharmacol 2011;71:718-26. PubMed
  6. Jeon H, Jang IJ, Lee S, et al. Apple juice greatly reduces systemic exposure to atenolol. Br J Clin Pharmacol 2012 May 11. doi: 10.1111/j.1365-2125.2012.04324.x. [Epub ahead of print]. PubMed
  7. Akamine Y, Miura M, Komori H, et al. Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers. Eur J Clin Pharmacol. 2014 Sep;70(9):1087-95. PubMed
Moderate

ANTIDIABETES DRUGS

2 of 2

Simvastatin, Sitagliptin also falls under ANTIDIABETES DRUGS.

Theoretically, consuming apple juice with antidiabetes drugs might interfere with blood glucose control.
Clinical research suggests that consuming apples or drinking apple juice can raise blood glucose levels, with the effects of drinking apple juice being more significant than consuming apples.
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

Juvisync is a combo pill that pairs sitagliptin (a diabetes medicine that helps lower blood sugar) with simvastatin (a cholesterol drug). The interaction on file is really about the diabetes half. The idea is simple: apple juice, and to a smaller degree apples themselves, contain natural sugars that can nudge your blood sugar upward. If you're drinking a lot of juice, that could work against what your sitagliptin is trying to do, making it a bit harder to keep glucose in a good range.

Keep in mind this is theoretical, based on how the sugars behave rather than strong studies. A fresh apple now and then is fine for most people. If you drink apple juice regularly, mention it to your pharmacist or doctor and keep an eye on your readings.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Asp, N. G., Agardh, C. D., Ahren, B., Dencker, I., Johansson, C. G., Lundquist, I., Nyman, M., Sartor, G., and Schersten, B. Dietary fibre in type II diabetes. Acta Med Scand Suppl 1981;656:47-50. 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

Apple Also Interacts With Other Medications

Apple has 46 major, 253 moderate known drug interactions in our database — the Simvastatin, Sitagliptin one above is among them. If you take anything else, check it against the full list below.

Major 46 Moderate 253 No known interaction 2,531 (incl. Simvastatin, Sitagliptin)
Taking anything else?

Check Another of Your Medications Against Apple

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

From our Q&A

Questions About Apple or Simvastatin, Sitagliptin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Apple or Simvastatin, Sitagliptin, 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 Simvastatin, Sitagliptin

This page covers Apple only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Simvastatin, Sitagliptin page lists 362 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 8 major · 304 moderate · 50 minor.

From our pharmacist’s overview on the Simvastatin, Sitagliptin page

“Juvisync pairs simvastatin for cholesterol with sitagliptin for type 2 diabetes, and that combination carries 362 supplement interactions on file, eight rated major, so read this page with real care rather than a quick skim. Grapefruit stands out as the everyday hazard; it blocks the enzyme that clears simvastatin, raising statin level…”

Reviewed by 2 · Jul 18, 2026

Open the Simvastatin, Sitagliptin interaction page

One more smart check

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

We hold 2,841 real supplement products containing Apple, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Apple. Your product may carry other ingredients that interact with Simvastatin, Sitagliptin too, on top of Apple — 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 Apple and Simvastatin, Sitagliptin 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 Apple
Top 10%

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

29 days ago today
Medication Simvastatin, Sitagliptin
Steady interest

#1,735 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 Apple

What is Apple?

Apple
  • General nutrition and fiber intake
  • Heart and cholesterol health
  • Blood sugar and weight management
  • Digestive regularity
  • Antioxidant support

Apples are a nutritious whole food that provides fiber, vitamins, and antioxidant plant compounds, and eating them regularly fits well into a healthy diet. While research suggests apples may support heart and digestive health, most claims about concentrated apple supplements or extracts are not strongly proven, so enjoy apples as food and talk with your pharmacist before using high-dose products.

Read the full Apple monograph & all interactions
Keep checking

Other Drugs & Apple

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

46Major
253Moderate
0Minor
2,530No known interaction
46 Major 253 Moderate 2,530 No interaction
Major

46 interactions

Moderate

253 interactions

Showing 60 of 253 moderate interactions — see all 253 on the Apple page.

No interaction 2,530 drugs checked — show the list

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

Showing the 60 most looked-up of 2,530 medications checked with no known interaction — see the full Apple list.

See the full Apple interactions page
See every supplement checked against Simvastatin, Sitagliptin, 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
Apple monograph › Uses, safety, and every drug interaction in one place Simvastatin, Sitagliptin supplement interactions › Every supplement checked against Simvastatin, Sitagliptin, 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 Apple and Simvastatin, Sitagliptin Together: Common Questions

Can you take Apple with Simvastatin, Sitagliptin?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Apple and Simvastatin, Sitagliptin?
Simvastatin, Sitagliptin belongs to more than one drug category, and Apple interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Apple and Simvastatin, Sitagliptin interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

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

Still Have a Question About Simvastatin, Sitagliptin and Apple?

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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.