A comprehensive 2025 guide to all approved and investigational incretin-based obesity medications — where retatrutide fits, and how the field has evolved.
The table below covers all major GLP-1 class drugs — approved and investigational — ranked roughly by weight loss efficacy. Scroll horizontally on mobile.
| Drug | Brand Name | Company | Targets | Route | Avg. Weight Loss | FDA Status |
|---|---|---|---|---|---|---|
| Retatrutide ★ | TBD | Eli Lilly | GLP-1 + GIP + Glucagon | Weekly injection | ~24% (Phase 2, 48wk) | Phase 3 |
| Tirzepatide | Zepbound / Mounjaro | Eli Lilly | GLP-1 + GIP | Weekly injection | ~20–22% (72 wk) | ✓ Approved |
| Semaglutide | Wegovy / Ozempic | Novo Nordisk | GLP-1 | Weekly injection | ~15% (68 wk) | ✓ Approved |
| Orforglipron | TBD | Eli Lilly | GLP-1 | Daily oral pill | ~14–15% (Phase 2) | Phase 3 |
| Cagrilintide + Sema | CagriSema | Novo Nordisk | GLP-1 + Amylin | Weekly injection | ~25% (Phase 3 early) | Phase 3 |
| Liraglutide | Saxenda / Victoza | Novo Nordisk | GLP-1 | Daily injection | ~8% (56 wk) | ✓ Approved |
| Oral Semaglutide | Rybelsus | Novo Nordisk | GLP-1 | Daily oral pill | ~5% (diabetes label) | ✓ Approved (T2D only) |
| Exenatide | Byetta / Bydureon | AstraZeneca | GLP-1 | Daily / weekly inj. | ~3–5% | ✓ Approved (T2D) |
★ Retatrutide highlighted. Weight loss figures are approximate averages from pivotal trials — cross-trial comparisons should be interpreted with caution. "Approved" refers to FDA approval for obesity and/or type 2 diabetes.
The GLP-1 drug class has evolved rapidly over roughly 15 years, with each generation producing meaningfully better outcomes than the last. Understanding the generations helps contextualise where retatrutide sits.
Exenatide, liraglutide, and eventually semaglutide established that mimicking gut hormones could produce clinically meaningful weight loss. Semaglutide's ~15% weight loss in the STEP trials was a watershed moment, earning genuine comparison to surgical outcomes for the first time. Daily injections gave way to once-weekly formats, dramatically improving patient adherence.
Tirzepatide proved the dual-agonist concept decisively: adding GIP to GLP-1 produced ~20–22% weight loss — a step-change improvement. The SURMOUNT-1 trial established tirzepatide as the new benchmark, and its approval for obesity (Zepbound) and type 2 diabetes (Mounjaro) transformed Eli Lilly's commercial trajectory. Tirzepatide remains the best-in-class approved drug as of 2025.
Retatrutide leads this emerging generation by adding glucagon receptor agonism, pushing Phase 2 weight loss to ~24%. Novo Nordisk's CagriSema (combining semaglutide with the amylin analog cagrilintide) is also chasing this territory with early Phase 3 data suggesting ~25% weight loss. This generation is defined by multi-pathway approaches that push the ceiling toward — and potentially past — surgical weight loss outcomes.
The emerging benchmark: Bariatric surgery (gastric bypass) typically produces 25–35% sustained weight loss. For the first time, pharmacological approaches are entering this range — raising the question of whether surgery will remain the standard of care for severe obesity.
A parallel development to the injectable arms race is the push for effective oral GLP-1 drugs. Orforglipron (Lilly) and oral semaglutide at higher doses (Novo Nordisk's OIC-001) are both in late-stage development. These drugs won't match injectable triple agonists for weight loss magnitude, but their convenience advantage could dramatically expand the population who will accept and adhere to long-term treatment.
We've written dedicated comparison pages for each major matchup: