Two investigational drugs from the same company — one a convenient daily pill, one a powerful weekly injection. They're designed for different patients, not competition.
Both orforglipron and retatrutide are Eli Lilly drugs, but they represent completely different bets. Orforglipron asks: how do we make GLP-1 therapy accessible to everyone? Retatrutide asks: how much weight loss can we achieve if we add every possible metabolic pathway? These aren't competing products — they're designed to serve different patients with different needs and priorities.
| Category | Orforglipron | Retatrutide |
|---|---|---|
| Drug Type | Small-molecule oral GLP-1 | Peptide triple agonist (GLP-1 + GIP + Glucagon) |
| Administration | Once-daily oral pill | Once-weekly injection |
| Avg. Weight Loss | ~12.4% (72 wk, Phase 3) | ~24% (48 wk, Phase 2) |
| FDA Status | NDA submitted Dec 2025 | Phase 3 ongoing (TRIUMPH) |
| Expected Availability | 2026 (weeks away) | 2027 at earliest |
| Starting Price | $149/month | Unknown (not approved) |
| Needle Required | ✗ No | ✓ Yes |
| Liver Disease (MASH) | Indirect benefit | Direct hepatic mechanism |
| Energy Expenditure | Standard GLP-1 effect | Increased (glucagon pathway) |
| Global Access Potential | Very high (oral, stable) | Lower (injectable, cold chain) |
Timing matters enormously: Orforglipron could be FDA approved within weeks. Retatrutide won't be approved until 2027 at the earliest. For patients who need treatment now, orforglipron is the only one of these two that can help in the near term.
Retatrutide's ~24% Phase 2 weight loss vs orforglipron's ~12.4% is a massive difference on paper — roughly double. But several nuances matter. Retatrutide's 24% was in Phase 2; Phase 3 results may differ. Retatrutide's curves had not plateaued at 48 weeks, suggesting it may achieve more over longer treatment. And ~12% weight loss from an easy daily pill is still an extraordinary clinical result that most patients would be very happy with.
The meaningful question is whether a patient needs 12% vs 24% weight loss to achieve their health goals. For most patients with moderate obesity, 12% is sufficient. For those with severe obesity approaching bariatric surgery criteria, retatrutide's additional potency may justify the wait and injection burden.
One compelling scenario involves using both drugs sequentially — starting on orforglipron (available now, affordable, convenient), achieving significant initial weight loss, then considering a transition to retatrutide when it's approved for patients who need additional results. Lilly has already validated a step-down concept (injections → orforglipron for maintenance); a step-up concept is equally logical for the highest-need patients.
Want comprehensive coverage of retatrutide — including the TRIUMPH Phase 3 trial program, mechanism of action, and detailed comparisons? Visit our sister site Retatrutide-RX.com for everything about Eli Lilly's investigational triple agonist.