The Future of Oral Weight-Loss Medication: Does Oral Tirzepatide Work?

October 7, 2025 •

2 min read

With an estimated 2 billion people expected to be obese by 2035, the demand for effective weight management solutions is surging. The question on many minds is, does oral tirzepatide work as a convenient alternative to popular injections?

Quick Summary

Currently, a true oral version of the dual-agonist tirzepatide is not FDA-approved. However, clinical trials for a once-daily oral GLP-1 pill, orforglipron, show promising results for weight loss and diabetes management.

Key Points

No Oral Tirzepatide: There is currently no FDA-approved oral version of tirzepatide (Mounjaro/Zepbound).
Orforglipron is the Oral Alternative: The investigational oral drug is called orforglipron, which is a single GLP-1 agonist, not a dual GIP/GLP-1 agonist like tirzepatide.
Proven Efficacy: Phase 3 trials show orforglipron leads to significant weight loss (up to 12.4%) and improves blood sugar in type 2 diabetes.
Convenient Dosing: Orforglipron is a once-daily pill that can be taken without the food or water restrictions required by other oral GLP-1s like Rybelsus.
Common Side Effects: The most frequent side effects are mild-to-moderate gastrointestinal issues like nausea and diarrhea, especially during dose increases.
Future Availability: The manufacturer plans to submit orforglipron for regulatory approval for obesity in 2025 and for diabetes in 2026.
Compounded Versions Halted: The FDA has ordered a stop to the production of unapproved, compounded oral tirzepatide as of March 2025.

The Search for an Oral Alternative to Injectable Tirzepatide

Injectable tirzepatide (Zepbound, Mounjaro) is a successful treatment for chronic weight management and type 2 diabetes, acting as a dual agonist for GIP and GLP-1 receptors. These hormones regulate blood sugar and digestion, leading to significant weight loss.

There is currently no FDA-approved oral form of tirzepatide. The FDA has stopped compounding pharmacies from producing unapproved oral versions. The focus for an oral alternative from Eli Lilly is a different molecule, orforglipron.

Understanding Orforglipron: The Investigational Oral Pill

Orforglipron is an investigational, once-daily oral GLP-1 receptor agonist. Unlike tirzepatide, it only targets the GLP-1 receptor. As a small molecule pill, it offers convenient daily dosing without food or water restrictions.

Clinical Trial Efficacy of Orforglipron

Phase 3 trials show significant results for orforglipron.

For Weight Loss (ATTAIN-1): Participants taking the highest dose (36 mg) achieved a mean body weight reduction of 12.4% after 72 weeks. Nearly 40% of participants on this dose lost at least 15% of their body weight.
For Type 2 Diabetes (ACHIEVE-1): Orforglipron significantly reduced HbA1c levels and led to a mean body weight reduction of 7.6% on the 36mg dose in adults with early-stage type 2 diabetes.

Weight loss with oral orforglipron in trials is currently more modest than with high-dose injectable tirzepatide.

Comparison of Oral vs. Injectable Options


Feature	Injectable Tirzepatide (Zepbound)	Oral Orforglipron (Investigational)	Oral Semaglutide (Rybelsus)
Mechanism	Dual GIP and GLP-1 receptor agonist	Single GLP-1 receptor agonist	Single GLP-1 receptor agonist
Administration	Once-weekly subcutaneous injection	Once-daily oral pill	Once-daily oral pill
Dosing Convenience	Weekly dosing	Daily, with no food or water restrictions	Daily, on an empty stomach, 30 mins before food/drink
Weight Loss Efficacy	Up to ~22.5% mean weight loss	Up to ~12.4% mean weight loss	~5-7 lbs weight loss in trials
Common Side Effects	Nausea, diarrhea, vomiting, constipation	Nausea, diarrhea, vomiting, constipation	Nausea, stomach pain, diarrhea

Safety, Side Effects, and Future Availability

Orforglipron's safety profile is consistent with other GLP-1 agonists. Common side effects are gastrointestinal, such as nausea and diarrhea, usually mild-to-moderate and occurring during dose escalation. Discontinuation rates due to side effects were between 21-24% across doses in some studies.

Eli Lilly plans to seek regulatory approval for orforglipron for obesity in 2025 and type 2 diabetes in 2026. If approved, it could provide an important oral treatment option.

Conclusion

In summary, a true oral tirzepatide is not currently available. The focus is on orforglipron, a different oral GLP-1 agonist. While its weight loss results in trials are slightly less than injectable tirzepatide, orforglipron shows significant efficacy and offers a convenient oral option for obesity and type 2 diabetes, potentially improving access and adherence.

For more information on the development of this medication, you can visit the developer's site: Eli Lilly and Company.

Frequently Asked Questions

No, as of September 2025, there is no FDA-approved pill version of tirzepatide, the active ingredient in Mounjaro and Zepbound. The oral medication currently in late-stage trials is a different drug called orforglipron.

Orforglipron is an investigational, once-daily oral GLP-1 receptor agonist being developed by Eli Lilly. It is designed for chronic weight management and treating type 2 diabetes and works by mimicking the GLP-1 incretin hormone.

No, oral tirzepatide is not FDA-approved. Unapproved, compounded versions of oral tirzepatide were ordered to be discontinued by the FDA in March 2025 after the official drug shortage ended.

In Phase 3 clinical trials (ATTAIN-1), participants taking the highest dose of orforglipron achieved a mean weight reduction of 12.4% of their body weight over 72 weeks. This is compared to up to 22.5% for injectable tirzepatide.

The manufacturer, Eli Lilly, plans to submit orforglipron to regulatory agencies for approval starting in 2025 for obesity and 2026 for type 2 diabetes. The actual availability depends on the timing of this review and approval process.

No. Tirzepatide (Zepbound/Mounjaro) is an injectable that targets two hormones: GIP and GLP-1. Orforglipron is an oral pill that targets only the GLP-1 hormone.

The most common side effects reported in clinical trials are gastrointestinal issues, such as nausea, vomiting, diarrhea, and constipation. These are typically mild to moderate and occur most frequently when starting the medication or increasing the dose.

Both are oral GLP-1 agonists. However, orforglipron can be taken at any time without food or water restrictions. Rybelsus must be taken on an empty stomach at least 30 minutes before eating or drinking. Trial data also suggests orforglipron may offer more significant weight loss.