The oral pill vs. the world's most prescribed GLP-1 injection. Is the weight loss gap worth the convenience trade-off?
Semaglutide — sold as Ozempic for diabetes and Wegovy for obesity — is the most prescribed GLP-1 drug in the world and has transformed obesity medicine. Orforglipron is its most direct challenger in terms of patient population and indication. The central question: is a ~3 percentage point difference in weight loss worth a weekly injection, ~$1,200/month more in cost, and a cold storage requirement?
| Category | Semaglutide (Wegovy) | Orforglipron |
|---|---|---|
| Drug Type | Peptide-based GLP-1 agonist | Small-molecule GLP-1 agonist |
| Administration | Weekly injection | Once-daily oral pill |
| Avg. Weight Loss | ~15% (68 weeks, STEP-1) | ~12.4% (72 weeks, ATTAIN-1) |
| Food Restrictions | None (injectable) | None |
| FDA Approved | ✓ Yes (Wegovy 2021) | ✗ Pending — decision expected 2026 |
| Monthly Cost (self-pay) | ~$1,350/month | ~$149–399/month |
| Refrigeration Required | ✓ Yes | ✗ No |
| Needle Required | ✓ Yes | ✗ No |
| Cardiovascular Data | SELECT trial completed | Ongoing Phase 3 |
| Developer | Novo Nordisk | Eli Lilly |
The cost difference is staggering: At $149/month vs ~$1,350/month, orforglipron could be up to 9x cheaper than Wegovy for self-pay patients. For the millions of patients without insurance coverage for obesity drugs, this difference alone makes orforglipron transformative.
The ~3 percentage point difference (12.4% vs ~15%) sounds modest, but in real terms: for a 250lb person, that's roughly 31 lbs on orforglipron vs ~38 lbs on semaglutide. Both are clinically meaningful results. Both significantly exceed what was achievable with older obesity medications. For the vast majority of patients with obesity, 12% body weight loss produces significant health benefits including reduced blood pressure, improved cholesterol, better blood sugar control, and lower cardiovascular risk.
The question is really about the patient's personal priorities — maximum weight loss at higher cost and injection burden, or very good weight loss at a fraction of the cost with a daily pill.
You want the highest weight loss from an approved drug, have good insurance coverage, are comfortable with weekly injections, and want the backing of long-term cardiovascular outcome data (SELECT trial). Wegovy is also now approved for reducing cardiovascular events — an indication orforglipron hasn't yet earned.
You prefer a daily pill over weekly injections, are paying out of pocket and can't afford $1,350/month, have needle phobia, live somewhere with limited cold storage access, or want to use it as a maintenance therapy after achieving your weight loss goal on an injectable.