Drug & supplement interaction

Proteolytic Enzymes (proteases) + Metformin, Sitagliptin

Metformin, Sitagliptin brand names: Janumet, Janumet XR.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Proteolytic Enzymes (proteases) and Metformin, Sitagliptin in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the label for Metformin, Sitagliptin states a food rule worth keeping to.

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Interaction report

Proteolytic Enzymes (proteases) and Metformin, Sitagliptin

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Metformin, Sitagliptin and Proteolytic Enzymes (proteases) in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

Worth understanding: our licensed dataset holds no drug-interaction record for Proteolytic Enzymes (proteases) at all — not against Metformin, Sitagliptin, and not against any other medication we track. This verdict therefore rests on the absence of any recorded data, not on research that looked at this combination and found nothing. We cannot rule an interaction out.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Proteolytic Enzymes (proteases) safety at a glance

Proteolytic Enzyme... overall Use caution Generally well tolerated for most adults, but may cause digestive upset or allergic reactions.
Pregnancy Avoid Safety has not been established, so it is best avoided during pregnancy unless prescribed.
Breastfeeding Use caution There is little safety data during breastfeeding, so use is not recommended without medical advice.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Metformin, Sitagliptin and Proteolytic Enzymes (proteases)? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
What to actually watch for

What Proteolytic Enzymes (proteases) Itself Has Been Linked To

This is not an interaction — nothing below involves Metformin, Sitagliptin. It is the side-effect record for Proteolytic Enzymes (proteases) on its own, from the licensed Natural Medicines monograph. If something new turns up after you add Proteolytic Enzymes (proteases), this list is the first place to look. One entry is worth acting on rather than waiting out — marked below.

  • Wheezing Worth acting on Additional detail

    “Proteolytic enzymes are commonly found in laundry detergents and pre-spotter products. Rarely, protease specific IgE positive tests possibly related to these products have occurred. Exposure may be airborne or topical. In addition, in case reports, occupational exposure to the airborne proteolytic enzyme pepsin has resulted in allergic rhinoconjunctivitis or asthma.”

    Proteolytic Enzymes (proteases) · Natural Medicines adverse-effect record, reported in asthma.

    3 sources cited
    1. 102705. Weeks JA, Harper RA, Simon RA, Burdick JD. Assessment of sensitization risk of a laundry pre-spotter containing protease. Cutan Ocul Toxicol. 2011;30(4):272-9. PubMed
    2. 102706. Marquès LI, Lara S, Abós T, Bartolomé B. Occupational rhinitis due to pepsin. J Investig Allergol Clin Immunol. 2006;16(2):136-7. DOI
    3. 102707. Cartier A, Malo JL, Pineau L, Dolovich J. Occupational asthma due to pepsin. J Allergy Clin Immunol. 1984;73(5 Pt 1):574-7. PubMed

Everything above comes from the Natural Medicines adverse-effect record for Proteolytic Enzymes (proteases) — expand a row for the licensed statement it rests on. We read the ADVERSE REACTIONS section of Metformin, Sitagliptin’s FDA label too, and the two lists don’t meaningfully overlap — which is why no Metformin, Sitagliptin column appears here.

How to take them

Some Metformin, Sitagliptin Products Have a Food Rule — Proteolytic Enzymes (proteases) Should Not Break It

At least one FDA label for a product containing Metformin, Sitagliptin says to take it with food. If you take Proteolytic Enzymes (proteases) on an empty stomach out of habit, keep them separate — and take Metformin, Sitagliptin with a meal where the label says to.

This may not be true of your version. Food instructions belong to the product, not the ingredient: two Metformin, Sitagliptin products can carry different directions, and extended-release forms often differ from immediate-release ones. The label we read is quoted below — check the directions on your own box or bottle, or ask your pharmacist, for how to take the exact product you were given.

2 DOSAGE AND ADMINISTRATION Take sitagliptin and metformin hydrochloride extended-release tablets orally once daily with a meal.

From the Dosage and Administration section of the FDA label we read for Metformin, Sitagliptin — where that label names a specific product, the instruction is that product's.

A food rule is not an interaction — it is about how much of the medicine you absorb. The directions that came with your own product, and your pharmacist, outrank anything on this page.

Everything else you take

See Every Supplement That Interacts With Metformin, Sitagliptin

This page covers Proteolytic Enzymes (proteases) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Metformin, Sitagliptin 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, Sitagliptin page

“Many people prescribed metformin with sitagliptin (Janumet, Janumet XR) for type 2 diabetes also try herbs sold as blood sugar support, fenugreek among the most popular, and that habit is exactly where the risk on this page concentrates. Of 257 documented supplement interactions, 239 can push glucose in the same direction the medicatio…”

Reviewed by 2 · Jul 18, 2026

Open the Metformin, Sitagliptin interaction page

One more smart check

Taking Proteolytic Enzymes (proteases) as Part of a Dietary Supplement Product? Check It for Interactions

We hold 713 real supplement products containing Proteolytic Enzymes (proteases), each one broken down to its full ingredient list — and combination products often carry several ingredients besides Proteolytic Enzymes (proteases). Even though Proteolytic Enzymes (proteases) itself has no known interaction with Metformin, Sitagliptin, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Proteolytic Enzymes (proteases) and Metformin, 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 Proteolytic Enzymes (proteases)
Top 5%

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

29 days ago today
Medication Metformin, Sitagliptin
Top 25%

#620 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Proteolytic Enzymes (proteases) reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Proteolytic Enzymes (proteases) and Metformin, Sitagliptin records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Proteolytic Enzymes (proteases)

What is Proteolytic Enzymes (proteases)?

  • Digestion and bloating
  • Muscle soreness and exercise recovery
  • Inflammation and swelling
  • Sinus and respiratory congestion
  • Post-surgery or injury recovery

Proteolytic enzymes are proteins that help break down other proteins, and common examples include bromelain (from pineapple), papain (from papaya), trypsin, chymotrypsin, and pancreatin. People take them for digestion, inflammation, and muscle recovery, but the evidence is mixed and stronger for some uses (like aiding digestion in people who lack natural enzymes) than others. They are generally well tolerated, but talk with a pharmacist or doctor before use, especially if you have allergies, a bleeding risk, or are pregnant.

Enzymes sourced from fruit (pineapple, papaya), animal pancreas, or microbial/fungal fermentation · Capsules, tablets (often enteric-coated), powders

An interaction check asks whether these two react with each other — it does not ask whether Proteolytic Enzymes (proteases) is a good idea for someone in your situation. Here is what our Proteolytic Enzymes (proteases) record says about it on its own.

Proteolytic Enzymes (proteases): dosing

There is no single standardized dose for proteolytic enzyme supplements. Products vary widely in their source, strength, and how they measure enzyme activity (for example, units may be listed differently from one brand to another).Because of this, the best approach is to follow the directions on the product label and not exceed the recommended amount. Do not assume an over-the-counter product replaces a prescription pancreatic enzyme.

From our Proteolytic Enzymes (proteases) monograph — the full record covers uses, side effects and every documented interaction.

Read the full Proteolytic Enzymes (proteases) monograph & all interactions
Keep checking

Other Drugs & Proteolytic Enzymes (proteases)

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

0Major
0Moderate
0Minor
2,829No known interaction
No interaction 2,829 drugs checked — show the list
Evidence & sources

Proteolytic Enzymes (proteases) References

The 3 references that drive our Proteolytic Enzymes (proteases) monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Weeks JA, Harper RA, Simon RA, Burdick JD. Assessment of sensitization risk of a laundry pre-spotter containing protease. Cutan Ocul Toxicol. 2011;30(4):272-9. PubMed
  2. Marquès LI, Lara S, Abós T, Bartolomé B. Occupational rhinitis due to pepsin. J Investig Allergol Clin Immunol. 2006;16(2):136-7. DOI
  3. Cartier A, Malo JL, Pineau L, Dolovich J. Occupational asthma due to pepsin. J Allergy Clin Immunol. 1984;73(5 Pt 1):574-7. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Proteolytic Enzymes (proteases) and Metformin, Sitagliptin Together: Common Questions

Is it safe to take Proteolytic Enzymes (proteases) with Metformin, Sitagliptin?
We do not list a known interaction between Proteolytic Enzymes (proteases) and Metformin, Sitagliptin. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Should I take Proteolytic Enzymes (proteases) and Metformin, Sitagliptin at the same time of day?
At least one FDA label for a product containing Metformin, Sitagliptin says to take it with food. If you take Proteolytic Enzymes (proteases) on an empty stomach out of habit, keep them separate and take Metformin, Sitagliptin with a meal where the label says to. Food instructions belong to the product rather than the ingredient — two Metformin, Sitagliptin products can differ — so check the directions on your own box. This is about absorption, not an interaction.
Does Metformin, Sitagliptin interact with any supplements?
Yes. Metformin, Sitagliptin has documented interactions with 257 supplements in our database — Proteolytic Enzymes (proteases) is not one of them. The Metformin, Sitagliptin interaction page linked on this page lists every one, ranked by severity.

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

Still Have a Question About Metformin, Sitagliptin and Proteolytic Enzymes (proteases)?

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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.