Orforglipron and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Simvastatin
Orforglipron
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.
Here's what's going on. Orforglipron (Foundayo) can raise the level of your cholesterol medicine simvastatin (Zocor) in your blood. Studies show it can roughly double or more the amount of active simvastatin your body is exposed to.
When simvastatin builds up, the main worry is muscle side effects, like aches, soreness, or weakness. The good news is this is very manageable. Your care team simply keeps your simvastatin dose in a safe range (no more than 20 mg a day) when you take these two together. Please don't change anything on your own. Just check in with your pharmacist or doctor, and let them know right away if you notice new muscle pain.
Effect: Orforglipron increases exposure to simvastatin acid (the active metabolite), with simvastatin AUC increased 2 to 2.5-fold and Cmax 2.3 to 2.5-fold when coadministered with orforglipron 17.2 mg once daily.
- Direction: Increased simvastatin exposure, raising risk of statin adverse effects (myalgia, myopathy, rare rhabdomyolysis, transaminase elevations).
- Mechanism: Unknown.
- Evidence: Probable, from drug interaction studies.
- Management: Do not exceed simvastatin 20 mg once daily with orforglipron. Monitor for muscle symptoms; consider CK if symptomatic.
What happens
Increased simvastatin exposure and an increased risk of simvastatin-related adverse reactions
Interaction Deep Dive
Taking orforglipron together with simvastatin can raise levels of the active metabolite simvastatin acid. In drug interaction studies, giving orforglipron (17.2 mg once daily) alongside simvastatin acid (the active metabolite) may raise the simvastatin AUC by 2 to 2.5-fold and the Cmax by 2.3 to 2.5-fold. When these agents are used together, simvastatin should be limited to no more than 20 mg once daily1.
Why it happens (mechanism)
Unknown
How to manage this interaction
This is manageable with a simple dosing limit. Because orforglipron raises simvastatin levels, the standard approach is capping the simvastatin dose.
- Your care team will typically keep simvastatin at no more than 20 mg once daily while you are also taking orforglipron.
- Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Watch for and report new or unexplained muscle pain, tenderness, or weakness, especially with dark urine or feeling unwell.
Ask your pharmacist or doctor to review your current simvastatin dose to confirm it fits this limit.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In studies of drug interactions, giving orforglipron (17.2 mg once daily) together with simvastatin acid (the active metabolite) may raise the simvastatin AUC by 2 to 2.5-fold and the Cmax by 2.3 to 2.5-fold 1.
Common questions
Can I take Orforglipron and Simvastatin together?
Taking orforglipron with simvastatin can more than double simvastatin levels and raise the risk of muscle side effects, so simvastatin should not exceed 20 mg daily when used together. Keep taking both as prescribed and report any muscle pain to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Orforglipron and Simvastatin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Orforglipron and Simvastatin interaction managed?
This is manageable with a simple dosing limit. Because orforglipron raises simvastatin levels, the standard approach is capping the simvastatin dose. Your care team will typically keep simvastatin at no more than 20 mg once daily while you are also taking orforglipron. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Watch for and report new or unexplain… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Orforglipron or Simvastatin 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 (1)
- Product Information: FOUNDAYO™ oral tablet, orforglipron oral tablet. Lilly USA LLC, Indianapolis, IN, 2026. DailyMed
Keep reading about Simvastatin
Keep reading about Orforglipron
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