No Oral Tirzepatide Currently Exists
Zepbound, with the active ingredient tirzepatide, is exclusively available as a weekly injectable medication and is not yet available in pill form. Zepbound is a synthetic peptide that mimics two important gut hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). For a medication like tirzepatide to be effective in pill form, it must be absorbed through the digestive system without being broken down. The large molecular structure of peptides makes them notoriously difficult for the body to absorb effectively from the gut.
Until recently, some compounding pharmacies created unauthorized oral versions of tirzepatide. However, the FDA has issued warnings about these compounded medications, stating they lack the safety and consistency of FDA-approved products. In March 2025, legal compounded versions were discontinued after the FDA declared the national tirzepatide shortage was over.
Orforglipron: The Closest Oral Candidate
Eli Lilly, the same company that manufactures Zepbound and Mounjaro, is actively developing a once-daily oral GLP-1 medication named orforglipron. This drug is a non-peptide, small-molecule agonist, making it more stable and absorbable via the oral route than peptide-based drugs like tirzepatide.
Clinical Trial Success
Orforglipron has shown very promising results in clinical trials:
- Weight Loss: In Phase 2 trials, participants experienced significant weight reduction, with a mean change of -9.4% to -14.7% over 36 weeks, compared to -2.3% for the placebo group.
- Diabetes Management: In Phase 3 trials for Type 2 diabetes, orforglipron significantly lowered glycated hemoglobin levels over 40 weeks.
- Efficacy: Eli Lilly has stated that the once-daily pill could offer weight loss results similar to its weekly injectable GLP-1 counterparts.
Anticipated Approval
Eli Lilly plans to submit orforglipron for global regulatory review by the end of 2025. If approved, it would offer a convenient, needle-free alternative for weight management and diabetes, potentially expanding access and improving adherence for patients who prefer pills.
How Orforglipron Compares to Injectable Zepbound
While not the same molecule, orforglipron is being developed as a functional oral counterpart to injectable GLP-1 and GIP drugs like Zepbound. The key differences are summarized below.
| Feature | Orforglipron (Oral Candidate) | Tirzepatide (Zepbound, Injectable) |
|---|---|---|
| Drug Type | Small-molecule agonist (non-peptide) | Peptide agonist |
| Mechanism | Activates GLP-1 receptors only (single agonist) | Activates both GLP-1 and GIP receptors (dual agonist) |
| Administration | Once-daily pill | Once-weekly injection |
| FDA Approval | Currently under regulatory review | FDA-approved |
| Weight Loss Potential | Significant, shown in clinical trials to be comparable to injections | Highly effective; patients lost an average of 21% of body weight in clinical trials |
| Side Effects | Common GI issues (nausea, diarrhea, etc.), primarily during dose escalation | Common GI issues (nausea, diarrhea, constipation) |
Other Oral Alternatives for Weight Management
For those seeking an oral option today, there are several alternatives to consider. It's important to note these medications have different mechanisms and may result in less weight loss than Zepbound.
- Rybelsus (Oral Semaglutide): An oral GLP-1 agonist approved for Type 2 diabetes, it contains the same active ingredient as injectable Wegovy. It is taken daily on an empty stomach and is less potent for weight loss than the injectable forms. However, higher doses for weight management are being studied, with potential FDA approval in 2026.
- Contrave (naltrexone/bupropion): A combination pill that works to reduce appetite and curb cravings. It is more readily available than GLP-1 injections but may lead to less significant weight loss.
- Qsymia (phentermine/topiramate ER): This combination medication reduces appetite and is taken as a once-daily pill. Weight loss with Qsymia is generally less than with Zepbound injections.
- Xenical (orlistat): Available as a prescription or over-the-counter (Alli), this medication blocks fat absorption and works differently from GLP-1 agonists.
Weighing Oral vs. Injectable Options
The choice between an oral and injectable medication depends on individual preferences and medical needs. Oral alternatives offer a major advantage in convenience, eliminating the need for self-injections. This can improve patient comfort and adherence, which is crucial for long-term treatment. However, oral versions can be affected by food and other oral medications, requiring strict timing for optimal absorption. While recent oral candidates like orforglipron show very promising results, injectable medications currently provide the most potent weight loss effects. Discussing all potential options with a healthcare provider is essential to determine the most suitable path for you.
Conclusion
While there is currently no FDA-approved oral version of Zepbound (tirzepatide), significant progress is being made in the development of oral alternatives. Eli Lilly's daily pill, orforglipron, is a promising non-peptide GLP-1 agonist nearing regulatory review, with clinical trial data suggesting comparable efficacy to weekly injections. In the meantime, alternatives like oral semaglutide (Rybelsus) for diabetes or other oral medications for weight management can be considered. The future promises more convenient, effective oral options for those who prefer to avoid injections, but for now, Zepbound remains an injectable-only therapy.
