Next-Generation GLP-1 Drugs Compared
Side-by-side comparison of semaglutide, tirzepatide, and all five major pipeline drugs — mechanism, efficacy, dosing format, approval status, and head-to-head analysis.
Semaglutide (Wegovy) and tirzepatide (Zepbound) are available through licensed telehealth providers in most states.
All 7 Drugs Side by Side
| Drug | Mechanism | Form | Avg Weight Loss | Phase | Est. Available | Key Edge |
|---|---|---|---|---|---|---|
| Semaglutide (Wegovy) | GLP-1 | Weekly inj. | ~15% | Approved | Now | Most studied; long safety record |
| Tirzepatide (Zepbound) | GLP-1 + GIP | Weekly inj. | ~20–22% | Approved | Now | Highest efficacy of approved drugs |
| Retatrutide | GLP-1+GIP+Glucagon | Weekly inj. | ~24% | Phase 3 | 2027–2028 | Highest weight loss in trials |
| CagriSema | GLP-1 + Amylin | Weekly inj. | 22.7% | Phase 3 | 2026–2027 | Strongest Phase 3 data so far |
| Orforglipron | GLP-1 (oral) | Daily pill | ~15% | Phase 3 | 2026–2027 | No injection; no food timing |
| MariTide | GLP-1/GIP block | Monthly inj. | ~20% | Phase 3 | 2027–2028 | Once-monthly — adherence advantage |
| Amycretin | GLP-1+Amylin oral | Daily pill | ~13% (12wk) | Phase 2 | 2029–2030 | Oral dual-agonist — if it survives trials |
Key Comparisons
Retatrutide vs. Semaglutide (Wegovy / Ozempic)
The most-searched comparison. Phase 2 data suggests roughly twice the weight loss — but semaglutide is approved today and retatrutide is 2+ years away.
| Retatrutide | Semaglutide (Wegovy) | |
|---|---|---|
| Mechanism | GLP-1 + GIP + Glucagon | GLP-1 |
| Avg weight loss | ~24% (Phase 2, 48 wk) | ~15% (Phase 3, 68 wk) |
| Dosing | Weekly injection | Weekly injection |
| FDA approved | No (Phase 3) | Yes |
| Available now | No (2027–2028) | Yes — telehealth |
| Verdict | Semaglutide is your option today. Retatrutide may offer meaningfully better results when approved — but 2+ years of waiting means 2+ years without treatment benefit. | |
Orforglipron vs. Ozempic / Wegovy
Can a pill match an injection? Phase 2 data suggests comparable weight loss — without the needle or the strict food timing of Rybelsus.
| Orforglipron | Ozempic / Wegovy | Rybelsus (oral sema) | |
|---|---|---|---|
| Form | Daily pill (no restrictions) | Weekly injection | Daily pill (strict timing) |
| Avg weight loss | ~15% | ~12–15% | ~5–8% |
| Food restrictions | None | None | 30-min fast required |
| Approved for obesity | No | Wegovy: Yes / Ozempic: No | No (diabetes only) |
| Available now | No | Yes | Yes |
CagriSema vs. Tirzepatide (Zepbound)
The closest head-to-head in the pipeline. Both combine two hormonal pathways and achieve ~22% weight loss. Tirzepatide is approved. CagriSema is not yet.
| CagriSema | Tirzepatide (Zepbound) | |
|---|---|---|
| Mechanism | GLP-1 + Amylin | GLP-1 + GIP |
| Avg weight loss | 22.7% (Phase 3) | ~20–22% (Phase 3) |
| Injection frequency | Weekly | Weekly |
| FDA approved | No (Phase 3) | Yes |
| Available now | No (2026–2027) | Yes — telehealth |
| Verdict | Very similar efficacy profile. Tirzepatide is available right now. CagriSema may offer incremental benefit for specific patient populations when approved. | |
MariTide vs. Tirzepatide (Monthly vs. Weekly)
Similar weight loss, fundamentally different dosing frequency. The adherence question is the key differentiator.
| MariTide | Tirzepatide (Zepbound) | |
|---|---|---|
| Dosing | Once monthly | Once weekly |
| Avg weight loss | ~20% (Phase 2) | ~20–22% (Phase 3) |
| Drug type | Bispecific antibody | Peptide |
| Available now | No (2027–2028) | Yes |
| Verdict | For patients who struggle with weekly injection adherence, MariTide's monthly format could be transformative. Tirzepatide achieves comparable results right now. | |
The Bottom Line
Every drug in this comparison that outperforms current approved options is still 1–3 years from availability at best. The drug most likely to be approved first (CagriSema or Orforglipron) achieves results comparable to tirzepatide — which is already available. The most rational path: access what exists today through a licensed provider, and reassess as new drugs reach approval.
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