Drug & supplement interaction

Lysine + Metformin, Sitagliptin

Metformin, Sitagliptin brand names: Janumet, Janumet XR.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Lysine 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, and the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Lysine 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 Lysine 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.

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.

Lysine safety at a glance

Lysine overall Use caution Generally well tolerated at typical doses, but high amounts may cause stomach upset and long-term safety is not well studied.
Pregnancy Use caution Lysine from food is fine, but supplement safety in pregnancy is not well studied, so check with your doctor first.
Breastfeeding Use caution There is not enough reliable information on supplement use while breastfeeding, so caution is advised.

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

Still wondering about combining Metformin, Sitagliptin and Lysine? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Metformin, Sitagliptin

Interactions in our licensed database are recorded against drug classes, not just single drug names. Metformin, Sitagliptin is filed under 5 classifications — including organic cation transporter 2 (oct2) substrates, antidiabetes drugs, oral drugs. Lysine has documented interactions with 1 drug class — the most serious being 5-ht4 agonists (minor) — and none of Metformin, Sitagliptin’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Lysine Does Interact With Other Medications

Lysine has 1 minor known drug interaction in our database — Metformin, Sitagliptin isn’t one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Lysine

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

What to actually watch for

No Interaction Found — But Data Suggests Lysine and Metformin, Sitagliptin May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

  • Kidney problems Worth acting on Additional detail

    Lysine

    “There is one case report of oral lysine use associated with tubulointerstitial nephritis progressing to chronic renal failure in a 44-year old female.”

    Lysine · Natural Medicines adverse-effect record, reported in kidney failure.

    1 source cited
    1. 1121. Lo JC, Chertow GM, Rennke H, Seifter JL. Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion. Am J Kidney Dis 1996;28:614-7. PubMed

    Metformin, Sitagliptin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin, Sitagliptin. Read the label on DailyMed ›

  • Stomach upset / Stomach pain / Diarrhea Additional detail

    Lysine

    “Orally, lysine has been reported to cause diarrhea and abdominal pain, including dyspepsia.”

    Lysine · Natural Medicines adverse-effect record, reported in diarrhea.

    5 sources cited
    1. 1114. Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg Oral Med Oral Pathol 1984;58:659-66. PubMed
    2. 1115. McCune MA, Perry HO, Muller SA, O'Fallon WM. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis 1984;34:366-73.
    3. 1116. DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Arch Dermatol 1984;120:48-51. DOI
    4. 1118. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:85-7.
    5. 1120. Griffith RS, Walsh DE, Myrmel KH, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 1987;175:183-90. DOI

    Metformin, Sitagliptin

    Listed in the ADVERSE REACTIONS section of the FDA label for Metformin, Sitagliptin. Read the label on DailyMed ›

Effects for Metformin, Sitagliptin come from the ADVERSE REACTIONS section of its FDA label; effects for Lysine come from the Natural Medicines adverse-effect record, quoted above. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

How to take them

Some Metformin, Sitagliptin Products Have a Food Rule — Lysine Should Not Break It

At least one FDA label for a product containing Metformin, Sitagliptin says to take it with food. If you take Lysine 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. Read the label on DailyMed ›

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

We hold 3,540 real supplement products containing Lysine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Lysine. Even though Lysine 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 Lysine 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 Lysine
Top 5%

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

29 days ago today
Medication Metformin, Sitagliptin
Top half

#1,049 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 Lysine reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Lysine 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 Lysine

What is Lysine?

  • Cold sores (herpes labialis)
  • Genital herpes outbreaks
  • Supporting protein and collagen formation
  • Calcium absorption support
  • General nutritional supplement

Lysine is an essential amino acid your body cannot make on its own, so it must come from food or supplements. People most often take extra lysine to try to prevent or shorten cold sores, but the evidence is mixed and far from conclusive. For most healthy people who eat enough protein, supplements are likely unnecessary, but they are generally considered low-risk at typical doses.

Amino acid (L-lysine) · Tablets, capsules, powder, topical creams (often combined with other ingredients)

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

Lysine: dosing

There is no single official supplement dose of lysine for any health condition, and a truly standardized dose has not been established for uses like cold sores. Products vary widely in how much they contain.The best approach is to follow the directions on the product label and not exceed the recommended amount.

From our Lysine monograph — the full record covers uses, side effects and every documented interaction.

Read the full Lysine monograph & all interactions
Keep checking

Other Drugs & Lysine

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

0Major
0Moderate
1Minor
2,828No known interaction
Minor

1 interaction

No interaction 2,828 drugs checked — show the list
Evidence & sources

Lysine References

The 7 references that drive our Lysine 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. Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg Oral Med Oral Pathol 1984;58:659-66. PubMed
  2. McCune MA, Perry HO, Muller SA, O'Fallon WM. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis 1984;34:366-73.
  3. DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Arch Dermatol 1984;120:48-51. DOI
  4. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:85-7.
  5. Griffith RS, Walsh DE, Myrmel KH, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 1987;175:183-90. DOI
  6. Lo JC, Chertow GM, Rennke H, Seifter JL. Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion. Am J Kidney Dis 1996;28:614-7. PubMed
  7. Smriga M, Torii K. L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15370-5.

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 Lysine and Metformin, Sitagliptin Together: Common Questions

Is it safe to take Lysine with Metformin, Sitagliptin?
We do not list a known interaction between Lysine 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.
Do Lysine and Metformin, Sitagliptin have any of the same side effects?
Yes — our sources link each of them separately to 4 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Should I take Lysine 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 Lysine 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.
How was the Lysine and Metformin, Sitagliptin combination checked?
Interactions in our licensed database are recorded against drug classes. Metformin, Sitagliptin is filed under 5 classifications, and Lysine has documented interactions with 1 drug class — none of Metformin, Sitagliptin's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Lysine interact with any other medications?
Yes. Lysine has 1 documented drug interaction in our database — Metformin, Sitagliptin is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Metformin, Sitagliptin interact with any supplements?
Yes. Metformin, Sitagliptin has documented interactions with 257 supplements in our database — Lysine 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 Lysine?

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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.