Weight-loss peptides compared: semaglutide, tirzepatide, retatrutide and CagriSema ranked by evidence
New injectable drugs for weight loss keep launching, and some of the most-talked-about ones — like retatrutide — aren't even approved yet. This guide ranks the real options by how well they've worked in trials, and is honest about which ones you can actually get a prescription for today.
By weight-loss magnitude in published trials, the order is retatrutide (up to ~30.3% in TRIUMPH-1) ahead of tirzepatide (~20–22%, the strongest approved option) and CagriSema (~20.4% in REDEFINE-1), ahead of semaglutide (~15%) and liraglutide (~5–8%). But magnitude isn't the whole answer: retatrutide and CagriSema are not FDA-approved — retatrutide's Lilly is not expected to file until Q1 2027, with approval unlikely before late 2027 or 2028, and Novo Nordisk's CagriSema NDA was only submitted in December 2025. Today, tirzepatide is the strongest drug you can actually be prescribed.
- Retatrutide, a GLP-1/GIP/glucagon triple agonist, produced the largest weight loss of any peptide tested to date — up to 30.3% in the Phase 3 TRIUMPH-1 trial — but is not approved and won't be for at least another year or two.
- Tirzepatide (Mounjaro, Zepbound) is the strongest weight-loss peptide you can currently be prescribed, and it beats semaglutide in every published head-to-head.
- CagriSema, a fixed-dose combination of cagrilintide (amylin) and semaglutide, filed for FDA approval in December 2025 after showing ~20.4% weight loss at 68 weeks in REDEFINE-1 (n=3,417) — a different mechanism worth knowing about even before it's approved.
- Retatrutide's Phase 3 data shows a dose-dependent side effect not consistently reported with the other molecules — dysesthesia, an abnormal skin sensation, at up to 20.9% at the highest dose.
- Cross-trial comparisons are not head-to-head trials. Different populations, durations and designs mean this ranking is directional, not a precise league table.
The landscape: what's approved and what isn't
Weight-loss peptides, status as of September 2026
| Molecule | Brand(s) | Mechanism | Status |
|---|---|---|---|
| Semaglutide | Ozempic, Wegovy | GLP-1 receptor agonist | Approved (diabetes and weight management) |
| Tirzepatide | Mounjaro, Zepbound | GLP-1 + GIP dual agonist | Approved (diabetes and weight management) |
| Liraglutide | Saxenda | GLP-1 receptor agonist, once-daily | Approved — older, largely superseded on efficacy |
| Retatrutide | Unbranded (Eli Lilly) | GLP-1 + GIP + glucagon triple agonist | Investigational — BLA expected Q1 2027 |
| Cagrilintide + semaglutide | CagriSema (Novo Nordisk) | GLP-1 + amylin analogue | Investigational — NDA filed December 2025 |
Ranked by weight-loss magnitude in trials
Headline results, by trial
| Molecule | Trial | N | Weight loss | Duration |
|---|---|---|---|---|
| Retatrutide (12 mg) | TRIUMPH-1, Phase 3 | Not yet published in full | Up to 30.3% | ~80 weeks |
| Tirzepatide (15 mg) | SURMOUNT programme | Multiple trials | ~20–22% | 72 weeks |
| CagriSema | REDEFINE-1, Phase 3 | 3,417 | ~20.4% | 68 weeks |
| Semaglutide (2.4 mg) | STEP programme | Multiple trials | ~15% | 68 weeks |
| Liraglutide (3.0 mg) | SCALE programme | Multiple trials | ~5–8% | 56 weeks |
Retatrutide in detail: the drug "supposed to go out"
Retatrutide is Eli Lilly's triple agonist — it activates GLP-1, GIP and glucagon receptors, adding a third mechanism on top of what tirzepatide already does. The added glucagon activity is thought to contribute an energy-expenditure effect on top of appetite suppression, which is the most likely explanation for why it has produced the largest weight-loss numbers of any drug in this class so far.
Retatrutide: where things actually stand
| Question | Answer |
|---|---|
| Is it FDA-approved? | No |
| When will it be filed? | Lilly named Q1 2027 for its Biologics License Application, per its July 2026 pipeline update |
| When might it be approved? | Realistically late 2027 or 2028, allowing for a standard 10–12 month FDA review after filing |
| Can I get it now? | Only through a clinical trial, or Lilly's limited early-access programme for some patients — not a standard prescription |
| What has it shown? | Up to 30.3% weight loss at the highest dose in TRIUMPH-1; Lilly has said its full Phase 3 package now supports registrations for obesity, obstructive sleep apnea and knee osteoarthritis |
Side effects, from the Phase 3 programme
- Nausea: 42.4% (TRIUMPH-1, highest dose) — varied by trial, from 22.4% to 43.2% across the four TRIUMPH studies.
- Diarrhoea: 32.0%; constipation: 26.1%; vomiting: 25.3% (TRIUMPH-1, highest dose).
- Dysesthesia — an abnormal skin sensation — is a dose-dependent signal that emerged in TRIUMPH-4: 8.8% at 9 mg, 20.9% at 12 mg. This has not been consistently reported with semaglutide or tirzepatide at comparable rates.
- Discontinuation for adverse events ranged from 3.8% to 18.2% across the four Phase 3 trials, rising with dose.
CagriSema: a different mechanism, also not approved yet
CagriSema pairs cagrilintide, a long-acting amylin analogue, with semaglutide in a fixed-dose combination — the first attempt to combine an amylin mechanism with GLP-1 rather than adding a second incretin receptor the way tirzepatide and retatrutide do. Novo Nordisk filed for FDA approval in December 2025, based on REDEFINE-1: 3,417 adults with obesity lost an average 20.4% of body weight at 68 weeks, against 3.0% on placebo, with 91.9% of participants achieving at least 5% weight loss.
If approved, it would be the first FDA-approved combination of a GLP-1 receptor agonist and an amylin analogue for weight management — a genuinely different mechanism from the dual- and triple-agonist drugs above, and one worth knowing about even while its approval is pending.
Which one fits which situation
Ranked on: fit for a stated goal against the current evidence and, critically, current availability — not a quality league table where the newest investigational drug automatically wins.
| # | Option | Verdict | Grade |
|---|---|---|---|
| 1 | You want the strongest option you can actually be prescribed today | Tirzepatide | — |
| 2 | Cardiovascular risk reduction is the priority, not the scale | Semaglutide | — |
| 3 | You're tracking retatrutide because you've heard it's better | It likely will be — once it's approved | — |
| 4 | GLP-1 side effects haven't worked for you | Watch CagriSema, cautiously | — |
| 5 | Budget or a long safety track record is the binding constraint | Liraglutide, with realistic expectations | — |
- 01
You want the strongest option you can actually be prescribed today
TirzepatideApproved, with the strongest published weight-loss results of any drug you can currently get a prescription for. Retatrutide's bigger numbers don't matter if it isn't available to you.
- 02
Cardiovascular risk reduction is the priority, not the scale
SemaglutideThe deepest cardiovascular outcomes evidence in this class comes from semaglutide's SELECT trial. Longer track record matters when the goal is risk reduction rather than maximum weight loss.
- 03
You're tracking retatrutide because you've heard it's better
It likely will be — once it's approvedThe Phase 3 data is genuinely the strongest in the class. The honest answer to "when can I get it" is late 2027 at the earliest, through a standard prescription, or a clinical trial before that.
- 04
GLP-1 side effects haven't worked for you
Watch CagriSema, cautiouslyA genuinely different mechanism (amylin plus GLP-1) is worth knowing about if the GLP-1-driven side effects have been the problem — but it's still pending approval, filed only in December 2025.
- 05
Budget or a long safety track record is the binding constraint
Liraglutide, with realistic expectationsThe oldest approved option in this class, with the longest real-world safety record — and the weakest efficacy of the group. A once-daily injection for roughly a third of the weight loss of the newer drugs.
Frequently asked questions
What is the strongest weight-loss peptide available right now?
Among drugs you can actually be prescribed, tirzepatide (Mounjaro, Zepbound) has the strongest published results, at roughly 20–22% weight loss in the SURMOUNT trials. Retatrutide has shown larger numbers — up to 30.3% in TRIUMPH-1 — but it is not FDA-approved and isn't available through a standard prescription.
Is retatrutide FDA approved?
No. Eli Lilly's July 2026 pipeline update named Q1 2027 as the target for submitting its Biologics License Application. A standard FDA review after filing runs 10–12 months, which puts realistic approval in late 2027 or 2028 — and that timeline can slip further.
When will retatrutide be available to the public?
Not before its FDA filing, expected Q1 2027, plus a review period of roughly a year — so late 2027 at the earliest through a normal prescription. Before that, access is limited to clinical trial participants and a small early-access programme Lilly has offered to some patients. Anything sold online outside those channels is not the studied product.
What is CagriSema and is it approved?
CagriSema is Novo Nordisk's fixed-dose combination of cagrilintide (an amylin analogue) and semaglutide. It is not yet approved — Novo Nordisk filed its FDA application in December 2025, based on the REDEFINE-1 trial, which showed roughly 20.4% average weight loss at 68 weeks in 3,417 adults with obesity.
Are weight-loss peptides safe to use long-term?
The approved ones — semaglutide, tirzepatide, liraglutide — have real long-term safety data, mostly showing a gastrointestinal side-effect profile that eases after dose escalation, alongside known rarer risks. The investigational ones, retatrutide and CagriSema, have safety data limited to their trial populations and durations so far; retatrutide's Phase 3 programme has surfaced a dose-dependent dysesthesia signal not consistently seen with the approved drugs, which is exactly the kind of finding ongoing trials exist to characterise before approval.
Keep reading
- Mounjaro vs Ozempic: which works better, and what it costs you
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