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Foundayo ™ (orforglipron) tablet
0.8 mg / 2.5 mg / 5.5 mg / 9 mg / 14.5 mg / 17.2 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Does Foundayo™ (orforglipron) interact with other medications?
Eli Lilly and Company has not systematically studied orforglipron with all medications. This response summarizes key orforglipron labeling information to support your assessment of potential interactions with concomitantly administered medications.
See important safety information, including boxed warning, in the attached prescribing information.
What Are the Key Orforglipron Labelling Information for Assessment of Interactions With Other Medications?
A prescriber should consider potential drug-drug interactions between orforglipron and all concomitantly used medications, vitamins, and supplements, and review their entire prescribing information before making a decision.
The following key prescribing information for orforglipron is provided to support your assessment of potential interactions with concomitantly administered medications.
ATTAIN-1 and ATTAIN-2 were randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of orforglipron in adults with obesity or overweight. ATTAIN-1 enrolled participants without type 2 diabetes (T2D) and ATTAIN-2 enrolled participants with T2D.1,2
These studies compared an investigational orforglipron capsule formulation with placebo during 72 weeks, plus a 2-week off-drug follow-up.1,2
This response presents safety data from the investigational orforglipron capsule formulation (1 mg, 3 mg, 6 mg, 12 mg, 24 mg, and 36 mg) shown as equivalent doses of once daily orforglipron tablets (0.8 mg, 2.5 mg, 5.5 mg, 9 mg, 14.5 mg, and 17.2 mg) approved in the United States.1-4
Content Overview
- What Are the Key Orforglipron Labelling Information for Assessment of Interactions With Other Medications?
- Cytochrome P450 (CYP)- and Transporter-Based Interactions With Orforglipron
- Delayed Gastric Emptying and Its Potential Impact on the Absorption of Other Medications
- Gastrointestinal Disorders
- Renal Side Effects
- Glucose Control
- Weight Loss
- Blood Pressure and Heart Rate
- Displacement From Protein Binding
- Enclosed Prescribing Information
- References
- Appendix
Cytochrome P450 (CYP)- and Transporter-Based Interactions With Orforglipron
In in vitro studies, orforglipron did not inhibit or induce CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6.3
Orforglipron is
- a substrate of CYP3A4 and CYP2J2, and
- not a substrate of CYP1A2, CYP2B6, CYP2C8, CYP2C19, CYP2D6, and CYP3A5.3
In addition, orforglipron did not inhibit OATP1B1, OATP1B3, OATP2B1, OAT1, OAT3, OCT1, OCT2, MATE1, or MATE2K.3
Orforglipron is
- a substrate of P-gp, OATP1B1, and OATP1B3, and
- not a substrate of BCRP or OCT1.3
Effects of Other Drugs on Orforglipron
Table 1 includes drug interactions and treatment recommendations where concomitant use of other drugs has clinically relevant effects on orforglipron. Table 2 outlines the results of studies that assessed the effects of other drugs on orforglipron pharmacokinetics, including definitive clinical trials and physiologically based pharmacokinetic (PBPK) simulations.3
Examples of CYP3A4 inhibitors, CYP3A4 inducers, and OATP1B1 inhibitors can be found in the Appendix.
Strong CYP3A4 Inhibitors |
|
Intervention |
The maximum dosage of orforglipron is 9 mg once daily when used concomitantly with a strong CYP3A4 inhibitor. Avoid concomitant use of orforglipron with strong CYP3A4 inhibitors that also inhibit OATP1B (e.g., ritonavir). |
Clinical Impact |
CYP3A4 inhibitors increase orforglipron exposure, which may increase the risk of orforglipron-associated adverse reactions. Strong CYP3A4 inhibitors that also clinically inhibit OATP1B are expected to significantly increase plasma concentrations of orforglipron, which may increase the risk of orforglipron-associated adverse reactions. |
Strong CYP3A4 Inducers |
|
Intervention |
Avoid concomitant use of orforglipron with strong CYP3A4 inducers. |
Clinical Impact |
Induction of CYP3A4 decreases orforglipron exposure, which may reduce the effectiveness of orforglipron. |
Moderate CYP3A4 Inducers |
|
Intervention |
Monitor orforglipron effectiveness and escalate dosage as needed when used concomitantly with moderate CYP3A4 inducers. |
Clinical Impact |
Induction of CYP3A4 decreases orforglipron exposure, which may reduce the effectiveness of orforglipron. |
Abbreviations: CYP3A4 = cytochrome P450 3A4; OATP1B = organic anion transporting polypeptide 1B.
| Concomitant Drug Category | Concomitant Drug (Dose) | Change in Orforglipron | |
| AUC | Cmax | ||
| Strong CYP3A4 inhibitors | Clarithromycin (500 mg twice daily) | ↑3.5-fold | ↑1.9-fold |
| Moderate CYP3A4 inhibitors | Verapamila (80 mg three times daily) | ↑2-fold | ↑1.6-fold |
| Strong CYP3A4 inducers | Carbamazepine (300 mg twice daily) | ↓82% | ↓55% |
| Moderate CYP3A4 inducers | Efavirenza (600 mg once daily) | ↓61% | ↓33% |
| Weak CYP3A4 inducers | Modafinila (200 mg once daily) | ↓16% | ↓7% |
| OATP1B inhibitors | Cyclosporine (200 mg twice daily) | ↑2.6-fold | ↑1.3-fold |
| P-gp inhibitors | Quinidine (200 mg twice daily) | ↓12% | ↓26% |
| Acid reducing agents | Esomeprazole (40 mg once daily) | No effect | No effect |
Abbreviations: AUC = area under the curve; Cmax = maximum plasma concentration; CYP3A4 = cytochrome P450 3A4; OATP1B = organic anion transporting polypeptide 1B; P-gp = P-glycoprotein.
Notes: Effects of other drugs on orforglipron that are considered clinically meaningful are presented in Table 1.
a Simulated using physiologically based pharmacokinetic modeling.
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Effects of Orforglipron on Other Drugs
Table 3 includes drug interactions and clinical interventions where orforglipron has clinically relevant effect on other drugs. Table 4 outlines the results of clinical assessments that evaluated the effect of orforglipron on other drugs.3
Simvastatin |
|
Intervention |
Do not exceed simvastatin 20 mg once daily when concomitantly used with orforglipron. |
Clinical Impact |
Use of orforglipron with simvastatin increased exposure of the active metabolite simvastatin acid two-fold. A two-fold increase in simvastatin acid exposure at the highest simvastatin dose could be clinically meaningful. |
Insulin or Insulin Secretagogue (e.g., Sulfonylurea) |
|
Intervention |
When initiating orforglipron, consider reducing the dose of concomitantly administered insulin or insulin secretagogues (e.g., sulfonylureas). |
Clinical Impact |
Orforglipron stimulates insulin release in the presence of elevated blood glucose concentrations which could increase the risk for hypoglycemia when used in combination with insulin or insulin secretagogues. |
Concomitant Drug Category |
Concomitant Drug (Dose) |
Orforglipron Dosage |
Change in Concomitant Drug |
|
AUC |
Cmax |
|||
Statin |
Simvastatin (prodrug) (20 mg) |
17.2 mg once daily |
up to ↓16% |
up to ↓27% |
Simvastatin acid (active metabolite) |
17.2 mg once daily |
↑2- to 2.5-fold |
↑2.3- to 2.5-fold |
|
Atorvastatin (40 mg) |
14.5 mg once daily |
↑1.5-fold |
↑0.9-fold |
|
BCRP substrate |
Rosuvastatin (20 mg) |
17.2 mg once daily |
↑1.7-fold |
↑1.3-fold |
CYP3A4 substrates |
Midazolam (200 mcg) |
17.2 mg once daily |
↑1.1-fold |
No effect |
P-gp substrates |
Digoxin (0.25 mg) |
17.2 mg once daily |
↑1.2-fold |
↑1.2-fold |
OATP1B substrates |
Endogenous OATP1B biomarker coproporphyrin-1 |
up to 14.5 mg once daily |
No effect |
No effect |
Abbreviations: AUC = area under the curve; BCRP = breast cancer resistance protein; Cmax = maximum concentration; CYP3A4 = cytochrome P450 3A4; OATP1B = organic anion transporting polypeptide 1B; P-gp = P-glycoprotein.
Notes: Effects of orforglipron on other drugs that are considered clinically relevant are presented in Table 3.
Concomitant use of orforglipron and simvastatin led to significant increases in the active metabolite simvastatin acid whether orforglipron was co-administered or dosing was staggered by 2 hours. The mechanism explaining why concomitant use of orforglipron increases simvastatin acid exposure is unknown.3
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Delayed Gastric Emptying and Its Potential Impact on the Absorption of Other Medications
Orforglipron delays gastric emptying and has the potential to affect the rate of absorption of other concomitantly administered oral drugs.3
The gastric emptying delay effect of orforglipron on acetaminophen Cmax was largest after the first dose of orforglipron 0.8 mg with acetaminophen Cmax decreased by 28%. The effect diminished after repeated dosing of orforglipron 17.2 mg.3
The delay is largest after the first dose and diminishes over time.3
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Oral Contraceptives
The effect of orforglipron on the absorption of oral contraceptives has not been evaluated in a clinical trial.3
Because delayed gastric emptying may affect the absorption of oral medications, advise patients using oral hormonal contraceptives to switch to a non-oral contraceptive method, or add a barrier method of contraception for 30 days after initiation with orforglipron and for 30 days after each dose escalation.3
Please consult the orforglipron US Prescribing Information and the prescribing information of concomitant medications, as they may provide further information.
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Gastrointestinal Disorders
Use of orforglipron has been associated with gastrointestinal adverse reactions, sometimes severe. In clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients treated with orforglipron (approximately 3%) than patients who received placebo (1%).3
Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.3
Orforglipron is not recommended in patients with severe gastroparesis.3
In a pool of ATTAIN-1 and ATTAIN-2, gastrointestinal (GI) adverse reactions occurred more frequently among patients treated with once daily orforglipron than placebo, specifically in
- 60% of participants receiving orforglipron 5.5 mg
- 68% of participants receiving orforglipron 9 mg
- 69% of participants receiving orforglipron 17.2 mg, and
- 37% of participants receiving placebo.3
Of the orforglipron-treated patients who reported GI adverse reactions, 60%, 36%, and 4% reported mild or moderate or severe adverse reactions, respectively.3
The incidence of nausea, vomiting, and diarrhea was higher during the orforglipron dosage escalation period and decreased over time.3
In the 2 placebo-controlled studies ATTAIN-1 and ATTAIN-2, constipation reactions occurred in
- 20% of participants receiving orforglipron 5.5 mg
- 27% of participants receiving orforglipron 9 mg
- 24% of participants receiving orforglipron 17.2 mg, and
- 9% of participants receiving placebo.3
It is unknown whether the risk of relevant constipation is increased in patients receiving concomitant medications such as opiates, antipsychotics, or others.
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Renal Side Effects
There have been reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with GLP-1 receptor agonists or orforglipron.3
The majority of the reported events occurred in patients who experienced GI adverse reactions leading to dehydration such as nausea, vomiting, or diarrhea.3
Monitor renal function in patients reporting adverse reactions to orforglipron that could lead to volume depletion, especially during dosage initiation and escalation of orforglipron.3
In a pool of ATTAIN-1 and ATTAIN-2, acute kidney injury was reported in 0.2% orforglipron-treated patients compared to 0.05% of placebo-treated patients.3
Please refer to the prescribing information of concomitant medications to understand if their use has been associated with gastrointestinal adverse reactions, potential risks of dehydration, volume depletion, and associated renal adverse reactions.
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Glucose Control
Orforglipron stimulates insulin release in the presence of elevated blood glucose concentrations, which could increase the risk for hypoglycemia when used in combination with insulin or insulin secretagogues. When initiating orforglipron, consider reducing the dose of concomitantly administered insulin or insulin secretagogues (eg, sulfonylureas).3
In ATTAIN-2, a trial of adults with type 2 diabetes and BMI ≥27 kg/m2,
- hypoglycemia (plasma glucose <54 mg/dL) was reported in 2% of patients treated with orforglipron versus in 0.2% of patients receiving placebo
- 1 patient treated with orforglipron and no patients receiving placebo reported severe hypoglycemia, and
- 7% of patients treated with orforglipron once daily in combination with sulfonylurea reported hypoglycemia compared with 0.5% of patients not taking a sulfonylurea.3
There is also increased risk of hypoglycemia in patients treated with orforglipron in combination with insulin.3
Hypoglycemia has also been associated with orforglipron and GLP-1 receptor agonists in adults without type 2 diabetes.3
Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia. In patients with diabetes, monitor blood glucose prior to starting orforglipron and during orforglipron treatment.3
The prescribing information of concomitant medications are the first resource to evaluate whether a concomitant medication has been associated with hypoglycemia or exacerbation of hyperglycemia.
Weight Loss
Concomitant use with another GLP-1 receptor agonist is not recommended.3
Orforglipron reduces body weight, with greater fat mass loss than lean mass loss.3
Eli Lilly and Company has no data on dose adjustments of other medications, vitamins, and supplements that are dosed by weight when these are used with orforglipron.
Please refer to the prescribing information of the concomitant medications to understand whether they are dosed by weight. Examples include, but are not limited to, valproate or levothyroxine.6,7
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Blood Pressure and Heart Rate
In the pooled ATTAIN-1 and ATTAIN-2 trials, hypotension occurred more frequently among patients taking orforglipron (2%) than patients taking placebo (0.5%).3
Hypotension was more frequently seen in orforglipron-treated patients on concomitant antihypertensive therapy (4%) compared to orforglipron-treated patients not on antihypertensive therapy (1%).3
In these pooled trials, tachycardia (tachycardia, heart rate increased, and sinus tachycardia) was reported in 3% of patients receiving orforglipron and 0.9% receiving placebo.3
Treatment with orforglipron resulted in a mean increase in heart rate of 4 to 5 beats per minute from baseline compared to 0.5 beat per minute in placebo.3
Please refer to the prescribing information of the concomitant medications to understand whether they are associated with changes in blood pressure or heart rate.
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Displacement From Protein Binding
Orforglipron plasma protein binding is greater than 99%. Orforglipron is only for oral use.3
No information is available on whether orforglipron will displace other medications that bind to plasma.
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Treatment Decision
Eli Lilly and Company cannot provide treatment recommendations beyond the prescribing information for the use of orforglipron in people who use other medications, vitamins, or supplements.
The health care practitioner should consider the potential risks and benefits of treatment options and monitor appropriately.
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Enclosed Prescribing Information
FOUNDAYO™ (orforglipron) tablets, for oral use, Lilly
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
- Wharton S, Aronne LJ, Stefanski A, et al; ATTAIN-1 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. N Engl J Med. 2025;393(18):1796-1806. https://doi.org/10.1056/NEJMoa2511774
- Horn DB, Ryan DH, Giljanovic Kis S, et al; ATTAIN-2 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2025;406(10522):2927-2944. https://doi.org/10.1016/S0140-6736(25)02165-8
- Foundayo [package insert]. Indianapolis, IN: Eli Lilly and Company; 2026.
- Ma X, Li YG, Raha S, et al. Pharmacokinetic bioequivalence of orforglipron tablets and capsules in healthy participants with obesity or overweight. Diabetes Obes Metab. Published online April 17, 2026. https://doi.org/10.1111/dom.70783
- Foundayo [package insert]. Indianapolis, IN: Eli Lilly and Company; 2026.
- Trac C, Zecopoulos A, Ross C, et al. Comparison of weight-based valproic acid dosing in treatment of mental illness among obese and nonobese patients. J Clin Psychopharmacol. 2024;44(5):468-471. https://doi.org/10.1097/JCP.0000000000001883
- Santini F, Pinchera A, Marsili A, et al. Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J Clin Endocrinol Metab. 2005;90(1):124-127. https://doi.org/10.1210/jc.2004-1306
- Drug interactions. UpToDate Lexidrug (Lexicomp). Wolters Kluwer. Accessed March 29, 2026. https://www.uptodate.com/contents/search?search
- For health care professionals: FDA’s examples of drugs that interact with CYP enzymes and transporter systems. US Food and Drug Administration. Updated January 20, 2026. Accessed April 27, 2026. https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems
- Busti AJ, et al. Common medications classified as weak, moderate and strong inhibitors of CYP3A4. EBMConsult. Updated October 2015. Accessed April 27, 2026. https://www.ebmconsult.com/articles/medications-inhibitors-cyp3a4-enzyme
- Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc. 2000;75(9):933-42. https://doi.org/10.4065/75.9.933
- Dayyih WA, Ani IA, Hailat M, et al. Review of grapefruit juice-drugs interactions mediated by intestinal CYP3A4 inhibition. J Appl Pharm Sci. 2024;14(05):059–068. https://doi.org/10.7324/JAPS.2024.160197
- Chen KF, Jones HM. PBPK perspective on alternative CYP3A4 inducers for rifampin. CPT Pharmacometrics Syst Pharmacol. 2022;11(12):1543-1546. https://doi.org/10.1002/psp4.12864.
- McFeely SJ, Ritchie TK, Yu J, et al. Inhibitors of organic anion-transporting polypeptides 1B1 and 1B3: clinical relevance and regulatory perspective. J Clin Pharmacol. 2020;60(8):1087-1098. https://doi.org/10.1002/jcph.1604
- Shitara Y. Clinical importance of OATP1B1 and OATP1B3 in drug-drug interactions. Drug Metab Pharmacokinet. 2011;26(3):220-7. https://doi.org/10.2133/dmpk.DMPK-10-RV-094
- OATP inhibitor list. StraightHealthcare.com. Accessed March 29, 2026. https://www.straighthealthcare.com/organic-anion-transporting-polypeptide.html
Appendix
Examples of CYP3A4 Inhibitors and Inducers and OATP1B1 Inhibitors
Table 5 is not intended to be an exhaustive list of CYP3A4 inhibitors or inducers or OATP1B1 inhibitors. Health care providers should exercise clinical judgment and consider external literature when evaluating potential drug‑drug interactions for individual patients.
| Drug Category | Drug Name |
|---|---|
| Strong CYP3A4 Inhibitors | Adagrasib, Atazanavir, Ceritinib, Clarithromycin, Cobicistat, Idelalisib, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Telithromycin, Tucatinib, Voriconazole |
| Moderate CYP3A4 Inhibitors | Aprepitant, Ciprofloxacin, Conivaptan, Crizotinib, Diltiazem, Delavirdine, Dronedarone, Erythromycin, Fluconazole, Fosamprenavir/amprenavir, Grapefruit juicea, Imatinib, Isavuconazole, Miconazole, Verapamil |
| Strong CYP3A4 Inducers | Apalutamide, Carbamazepine, Enzalutamide, Mitotane, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, St. John's Wort |
| Moderate CYP3A4 Inducers | Bosentan, Cenobamate, Dabrafenib, Efavirenz, Etravirine, Modafinil, Nafcillin, Oxcarbazepine |
| OATP1B1 Inhibitors | Atazanavir/ritonavir, Clarithromycin, Cobicistat, Cyclosporine, Daclatasvir, Darolutamide, Eltrombopag, Erythromycin, Fusidic acid, Gemfibrozil, Glecaprevir/pibrentasvir, Ketoconazole, Letermovir, Lopinavir/ritonavir, Paritaprevir/ritonavir, Rifampin, Ritonavir, Saquinavir, Simeprevir, Telithromycin, Teriflunomide, Tipranavir, Velpatasvir, Voxilaprevir |
Abbreviations: CYP = cytochrome P450; OATP = organic anion transporting polypeptide.
aGrapefruit juice inhibits intestinal CYP3A4 and is therefore not expected to cause an interaction with orforglipron that is metabolized by hepatic CYP3A4.
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Date of Last Review: April 24, 2026