Both are from Eli Lilly — one is today's best-in-class injectable, the other is tomorrow's most convenient pill. How do they compare?
This is a fascinating comparison because both drugs come from the same company. Tirzepatide (Mounjaro for diabetes, Zepbound for obesity) is Eli Lilly's current crown jewel — a weekly injectable dual agonist producing ~20–22% weight loss. Orforglipron is being developed alongside it as a daily oral option. Lilly appears to be positioning them for different patient segments rather than direct competition.
| Category | Tirzepatide (Zepbound) | Orforglipron |
|---|---|---|
| Drug Type | Peptide dual agonist (GLP-1 + GIP) | Small-molecule GLP-1 agonist |
| Administration | Weekly injection | Once-daily oral pill |
| Avg. Weight Loss | ~20–22% (72 weeks, SURMOUNT-1) | ~12.4% (72 weeks, ATTAIN-1) |
| FDA Approved | ✓ Yes — Obesity (2023), Diabetes (2022) | ✗ Pending — 2026 |
| Monthly Cost | ~$1,060/month | ~$149–399/month |
| Needle Required | ✓ Yes | ✗ No |
| Refrigeration | ✓ Yes | ✗ No |
| Sleep Apnea Approved | ✓ Yes (2024) | Under study |
| Maintenance Therapy | Not studied as step-down | ATTAIN-MAINTAIN: proven effective |
| Developer | Eli Lilly | Eli Lilly |
The step-down strategy: ATTAIN-MAINTAIN revealed a powerful treatment pathway — achieve maximum weight loss on tirzepatide, then step down to orforglipron for long-term maintenance. Patients switching from Zepbound to orforglipron maintained their weight loss with only a ~5kg difference over 52 weeks, at a fraction of the cost and without further injections.
At ~20–22% vs ~12.4%, tirzepatide produces substantially more weight loss than orforglipron. For a 270lb patient, that's roughly 55–60 lbs on tirzepatide vs ~33 lbs on orforglipron. This gap matters clinically — particularly for patients with severe obesity who may need maximum possible weight loss to avoid bariatric surgery or to achieve remission of serious conditions like type 2 diabetes or sleep apnea.
However, for many patients with moderate obesity, 12% weight loss delivers all the health benefits they need — reduced blood pressure, improved cholesterol, better glycemic control, and meaningful quality of life improvements.
You need maximum weight loss — particularly if you have severe obesity, are trying to avoid surgery, or have conditions like sleep apnea that require aggressive weight reduction. You're comfortable with weekly injections and have insurance coverage or can manage the ~$1,060/month cost.
Convenience and cost are your priorities. You prefer a daily pill to weekly shots. You're paying out of pocket. Or you want to use it as a maintenance strategy after achieving your goal weight on a more powerful injectable — a compelling and proven approach.