Gemfibrozil and Repaglinide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Repaglinide
Gemfibrozil
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased plasma concentrations of repaglinide
Interaction Deep Dive
Concomitant use of gemfibrozil with repaglinide is contraindicated due to the increase in repaglinide exposure24. In one study, concomitant administration of gemfibrozil and repaglinide caused an 8.1-fold increase in repaglinide AUC and prolonged the half-life almost 2.4-fold 3. Additionally, the CYP2C8 inhibition has been reported to last up to 12 hours after the last gemfibrozil dose despite plasma concentrations of gemfibrozil and its metabolite decreasing to less than 10% of its peak level 1.
Why it happens (mechanism)
Inhibition of CYP2C8-mediated repaglinide metabolism and OATP1B1-mediated repaglinide transport by gemfibrozil
Literature reports
2 reports — tap to read
a) Concomitant use of repaglinide and gemfibrozil (a CYP2C8 and OATP1B1 transporter inhibitor) resulted in an 8.1-fold increase in the repaglinide AUC. Additionally, the inhibition has been reported to last up to 12 hours after the last gemfibrozil dose despite plasma concentrations of gemfibrozil and its metabolite decreasing to less than 10% of its peak level 1.
b) A randomized crossover study in 12 healthy volunteers demonstrated that concomitant administration of gemfibrozil and repaglinide caused an 8.1-fold increase in repaglinide AUC and prolonged the half-life from 1.3 to 3.7 hours. The 4 men and 8 women (20 to 24 years old) received either gemfibrozil 600 mg, itraconazole 100 mg (first dose of 200 mg), both gemfibrozil and itraconazole, or placebo, twice a day for 3 days. On day 3, they received a single dose of repaglinide 0.25 mg, and plasma drug and blood glucose concentrations were measured for 7 hours. Itraconazole administration alone increased repaglinide AUC 1.4-fold. The combination of gemfibrozil and itraconazole increased the AUC 19.4-fold and increased the half-life to 6.1 hours. At 7 hours post dose, repaglinide AUC was 28.6 times higher in patients administered gemfibrozil, and 70.4 times higher in patients administered gemfibrozil plus itraconazole 3.
Common questions
Can I take Gemfibrozil and Repaglinide together?
Increased plasma concentrations of repaglinide Always confirm with your pharmacist or prescriber before making any change.
How serious is the Gemfibrozil and Repaglinide interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Gemfibrozil or Repaglinide need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (4)
- Tornio A, Neuvonen PJ, Niemi M, et al: Role of gemfibrozil as an inhibitor of CYP2C8 and membrane transporters. Expert Opin Drug Metab Toxicol 2017; 13(1):83-95. PubMed
- Product Information: PRANDIN(R) oral tablets, repaglinide oral tablets. Novo Nordisk Inc. (per FDA), Plainsboro, NJ, 2017. DailyMed
- Niemi M, Backman J, Neuvonen M, et al: Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 2003; 46:347-351. PubMed
- Product Information: repaglinide metformin HCl oral tablets, repaglinide metformin HCl oral tablets. Lupin Pharmaceuticals, Inc. (per DailyMed), Baltimore, MD, 2015.
Keep reading about Repaglinide
Keep reading about Gemfibrozil
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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