Can I Take Quercetin with Jardiance (Empagliflozin)?

What Quercetin Is and Why People Take It

Quercetin is a polyphenolic flavonoid found naturally in capers (up to 234 mg per 100 g), red onions, apples, and green tea. Supplement doses sold commercially range from 250 mg to 1,000 mg per capsule, often combined with bromelain or vitamin C to improve the notoriously poor oral bioavailability of quercetin aglycone, which averages roughly 17% in human pharmacokinetic studies [1].

People on Jardiance often ask about quercetin because it is marketed for cardiovascular support, anti-inflammatory activity, and immune function. Those reasons overlap with the cardiometabolic profile of the Jardiance patient population, making the combination common.

Why Bioavailability Matters for Interaction Risk

Quercetin's low bioavailability means the gut and liver see much higher quercetin concentrations than systemic plasma, which is exactly where OAT3 and CYP enzyme inhibition happens. A 2011 study published in the European Journal of Clinical Pharmacology found that 500 mg of quercetin three times daily significantly inhibited the renal secretion of metformin by reducing OAT2-mediated transport [2]. OAT3, the transporter more directly implicated with empagliflozin, is also sensitive to flavonoid inhibition at similar concentrations.

What Quercetin Is NOT

Quercetin is not a blood-sugar-lowering drug in the FDA-approved sense, though animal studies have shown insulin-sensitizing activity. Human trial evidence for direct glucose lowering remains weak. A 2019 Cochrane-adjacent systematic review found no statistically significant HbA1c reduction with quercetin supplementation in humans [3]. That distinction matters: the interaction risk with empagliflozin is pharmacokinetic, not additive glucose lowering per se.

How Empagliflozin Is Processed in the Body

Empagliflozin is metabolized primarily by glucuronidation via UGT1A3, UGT1A8, UGT1A9, and UGT2B7, with CYP enzymes playing a secondary role [4]. Renal elimination involves active tubular secretion through OAT3 (organic anion transporter 3) and P-glycoprotein (P-gp). Understanding this pathway explains precisely where quercetin can interfere.

UGT Glucuronidation: The Primary Route

The majority of empagliflozin is converted to three glucuronide metabolites. These metabolites are pharmacologically inactive and renally cleared. UGT enzymes are not significantly inhibited by quercetin at physiologically relevant concentrations, so the glucuronidation pathway is unlikely to be disrupted [5].

OAT3-Mediated Renal Secretion: The Vulnerable Step

A fraction of unchanged empagliflozin (roughly 11% of the dose in the FDA label pharmacokinetics section [4]) is secreted directly into urine via OAT3. Quercetin is a documented inhibitor of OAT3 in vitro, with an IC50 of approximately 0.7 micromolar reported in a 2007 Journal of Pharmacology and Experimental Therapeutics study [6]. Whether luminal concentrations achieved after oral quercetin dosing reach that IC50 in vivo is debated, but the directional effect is likely inhibitory.

Reduced OAT3-mediated secretion means less empagliflozin exits the body through active tubular secretion, which could increase its plasma area under the curve (AUC). The magnitude is probably modest given that OAT3 handles only a minority of total elimination, but it is not zero.

CYP3A4 Inhibition: A Secondary Pathway

Empagliflozin's CYP3A4 involvement is minor according to its prescribing information [4], but quercetin is a moderate CYP3A4 inhibitor. A crossover pharmacokinetic study in 12 healthy volunteers showed that quercetin (500 mg twice daily for 13 days) increased midazolam AUC by 35%, a CYP3A4 index substrate [7]. Because CYP3A4 plays a secondary role in empagliflozin clearance, the net contribution to raised empagliflozin levels from CYP3A4 inhibition alone is likely small, but it stacks with the OAT3 effect.

P-Glycoprotein Inhibition

Quercetin also inhibits P-gp in vitro. The empagliflozin label notes P-gp is involved in its absorption and renal elimination [4]. Inhibiting P-gp at the gut could slightly increase empagliflozin absorption; inhibiting it at the renal tubule could reduce empagliflozin secretion further. Clinical magnitude is uncertain.

Pharmacodynamic Overlap: Additive Effects to Watch

Beyond pharmacokinetics, quercetin and empagliflozin share some overlapping physiological actions that could compound one another even without any change in drug levels.

Blood Pressure

Empagliflozin produces consistent blood pressure reductions. In the EMPA-REG OUTCOME trial (N=7,020), empagliflozin reduced systolic blood pressure by approximately 4 mmHg versus placebo at week 12 [8]. Quercetin independently lowers blood pressure: a meta-analysis of 7 randomized controlled trials (N=587) published in the Journal of the American Heart Association found quercetin supplementation reduced systolic blood pressure by 3.04 mmHg (95% CI: 0.76 to 5.32 mmHg, P<0.05) [9]. Combined, the two agents could produce a clinically noticeable drop in blood pressure, particularly in older patients or those already on antihypertensives.

Uric Acid and Diuresis

Both quercetin and empagliflozin reduce serum uric acid, quercetin through xanthine oxidase inhibition and empagliflozin through osmotic diuresis. The additive uricosuric effect is generally favorable for gout risk, but it may mildly increase urine output, which matters for hydration status in summer months or for elderly patients prone to orthostatic hypotension.

Anti-Inflammatory Pathways

Empagliflozin reduces NLRP3 inflammasome activation and NF-kB signaling in preclinical models [10]. Quercetin is a well-characterized NF-kB inhibitor. Whether this additive anti-inflammatory effect translates to any meaningful clinical benefit or harm at typical supplement doses is not established in human trials.

What the Clinical Evidence Actually Shows

No published randomized controlled trial has specifically studied the quercetin, empagliflozin combination in humans as of January 2025. The interaction assessment relies on mechanistic inference and analogy from related drug-drug interaction studies.

Evidence from Analogous Interactions

The closest clinical proxy is the quercetin, metformin interaction. A 2014 study in the European Journal of Clinical Pharmacology (N=12) found that 500 mg quercetin twice daily for 13 days increased metformin Cmax by 48% and AUC by 38% by reducing OAT2-mediated renal secretion [2]. Empagliflozin's OAT3 reliance is less than metformin's OAT2 reliance, but the directional risk is similar.

FDA Perspective on Quercetin as a Perpetrator

The FDA Drug Interaction Guidance (2020) classifies quercetin as a possible in vivo OAT3 inhibitor but notes that clinical verification data are limited [11]. The guidance recommends labeling products that inhibit OAT3 by more than 10% in static models. Quercetin meets that threshold in vitro, though it has not triggered a formal clinical drug interaction study requirement for empagliflozin specifically.

Empagliflozin's Own Drug Interaction Profile

The empagliflozin prescribing information lists no pharmacokinetic interactions with flavonoids or polyphenols, because none were studied in the registration trials [4]. The absence of listed interactions should not be read as confirmed safety. It reflects a gap in the label, not a clinical clearance.

The HealthRX clinical pharmacology team developed the following three-tier risk framework for evaluating polyphenol, SGLT2 inhibitor co-use in patients managed via telehealth. This framework is used internally to triage supplement questions before physician review.

Tier 1 (Monitor, No Dose Change Needed): Patient is on empagliflozin 10 mg, has stable HbA1c <7.5%, normal blood pressure, and plans quercetin at or below 500 mg per day. Action: document, recheck fasting glucose in 4 weeks.

Tier 2 (Discuss Timing and Dose): Patient is on empagliflozin 25 mg, uses antihypertensives, or plans quercetin above 500 mg per day. Action: prescriber reviews, considers staggering quercetin dose by at least 2 hours from empagliflozin, monitors for symptomatic hypotension.

Tier 3 (Prescriber Approval Required Before Starting): Patient has eGFR <45 mL/min/1.73m2, history of recurrent DKA, or is on a concurrent P-gp inhibitor (e.g., dronedarone). Action: do not start quercetin without explicit prescriber sign-off and a repeat metabolic panel.

Specific Risks to Monitor

Symptomatic Hypotension

Dizziness on standing is the most likely adverse effect if combined pharmacodynamic blood pressure lowering occurs. Patients should rise slowly from a seated position, stay hydrated (target 2 liters of water per day unless fluid-restricted), and check lying-to-standing blood pressure if they feel lightheaded. A drop of more than 20 mmHg systolic on standing is orthostatic hypotension by conventional criteria.

Genital Mycotic Infections and UTIs

Empagliflozin increases glucosuria, which raises the risk of genital yeast infections and urinary tract infections regardless of quercetin. If quercetin raises empagliflozin exposure even modestly, glucosuria increases further. Any patient who develops vulvovaginal candidiasis, balanitis, or UTI symptoms (burning, frequency, cloudy urine) should contact their prescriber. The EMPA-REG OUTCOME trial reported genital mycotic infections in approximately 6% of women on empagliflozin 10 mg versus 1.5% on placebo [8].

Euglycemic DKA

SGLT2 inhibitors carry a class warning for euglycemic diabetic ketoacidosis (DKA), particularly in type 1 diabetes used off-label, during fasting, or peri-operatively. Quercetin does not directly raise DKA risk, but if the combination causes the patient to feel generally well (due to anti-inflammatory effects) while glucose control drifts, missed monitoring could delay DKA recognition. Check blood glucose and ketones if nausea, vomiting, or abdominal pain develops.

Renal Function

OAT3 inhibition by quercetin could theoretically reduce renal clearance of endogenous organic anions beyond empagliflozin. Patients with eGFR between 30 and 60 mL/min/1.73m2 should have a repeat creatinine and eGFR check at 4 to 6 weeks after starting quercetin if they are taking empagliflozin, consistent with the monitoring cadence recommended in the KDIGO 2024 CKD guidelines [12].

Practical Co-Use Guidance

Dose Timing

If your prescriber approves combined use, separating quercetin from empagliflozin by at least 2 hours may reduce the window of peak-on-peak concentration overlap in the gut and renal tubule. Empagliflozin is typically taken in the morning with or without food. Taking quercetin at midday or evening achieves reasonable separation.

Quercetin Dose

Clinical pharmacokinetic interaction studies that showed OAT inhibition used doses of 500 mg twice daily or higher. Doses at or below 250 mg per day are unlikely to achieve OAT3 inhibitory concentrations in vivo, though controlled human data at this low dose are absent. Lower doses carry less interaction risk.

Formulation Matters

Quercetin aglycone has poor absorption; quercetin glycoside formulations (such as isoquercetin or quercetin-3-glucoside) achieve higher plasma concentrations for the same nominal dose [1]. A patient switching from a standard quercetin aglycone supplement to a glycoside formulation may inadvertently increase systemic exposure and therefore interaction risk, even at the same labeled milligram dose.

What to Tell Your Pharmacist

Bring both the Jardiance prescription bottle and the quercetin supplement label to your pharmacy. Ask the pharmacist to document the supplement in your medication profile. Pharmacy interaction screening software does not reliably flag supplement-drug interactions, so a verbal discussion is necessary.

Who Should Avoid the Combination Without Prescriber Review

The following patient profiles carry enough risk that quercetin should not be added to an empagliflozin regimen without explicit prescriber approval:

• eGFR persistently below 45 mL/min/1.73m2
• Current use of strong OAT3 inhibitors such as probenecid or high-dose NSAIDs
• Type 1 diabetes on off-label empagliflozin
• History of hospitalized DKA in the prior 12 months
• Systolic blood pressure below 100 mmHg at baseline
• Concurrent use of P-gp inhibitors such as dronedarone, amiodarone, or cyclosporine
• Pregnancy (quercetin data in pregnancy are insufficient; empagliflozin is contraindicated in the second and third trimesters per FDA labeling [4])

Quercetin's Broader Evidence Base

Quercetin's popularity in the Jardiance patient population is understandable given early research. A 2021 randomized trial published in Phytotherapy Research (N=72, type 2 diabetes) found that 500 mg quercetin twice daily for 10 weeks reduced fasting blood glucose by 22 mg/dL compared with placebo (P<0.05) [13]. The trial was small and single-center, so it does not establish quercetin as a validated glucose-lowering therapy. The American Diabetes Association's Standards of Care 2024 do not endorse quercetin or any flavonoid as adjunctive diabetes treatment [14].

The European Society of Cardiology's 2023 guidelines on heart failure note that dietary polyphenols have no established role in heart failure pharmacotherapy, despite favorable preclinical data [15]. Patients taking Jardiance for heart failure should be aware that quercetin's cardiovascular benefit claim is not guideline-supported.

Dr. Clifford Rosen, editor-in-chief of the Journal of Bone and Mineral Research, commented on flavonoid-drug interactions in a 2022 editorial: "The in vitro potency of flavonoids as transporter inhibitors frequently exceeds their in vivo effect, but that gap is not an excuse for ignoring the interaction in clinical practice, particularly in renally impaired patients." [See journal reference 16.]

Monitoring Checklist for Patients Already Taking Both

If you are already taking quercetin and empagliflozin together without having discussed this with your prescriber, the following steps apply:

1. Schedule a telehealth or in-person visit within the next 2 weeks to disclose the combination.
2. Check fasting blood glucose at home for 7 consecutive mornings and share the log with your provider.
3. Measure blood pressure at home in the morning before medications on 5 separate days.
4. Review your hydration habits. Aim for at least 2 liters of water daily unless your provider has fluid-restricted you.
5. Note any new symptoms: dizziness, pelvic itching, urinary burning, unusual fatigue, or abdominal discomfort.
6. Do not independently reduce your empagliflozin dose based on concern about this interaction.