Weight-loss peptides compared: semaglutide, tirzepatide, retatrutide and CagriSema ranked by evidence
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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 (28.3% at 80 weeks in TRIUMPH-1, and up to 30.3% at 104 weeks in participants who started with a BMI of 35 or more) ahead of tirzepatide (~20–22%, the strongest approved option), with CagriSema (~20.4% in REDEFINE-1) and high-dose semaglutide (Wegovy HD 7.2 mg, ~19–21% in STEP UP) close behind, then standard-dose semaglutide (~15% at 2.4 mg) and liraglutide (~5–8%). But magnitude isn't the whole answer: retatrutide and CagriSema are not FDA-approved — retatrutide's maker, Eli 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 — 28.3% at 80 weeks in the Phase 3 TRIUMPH-1 trial, and up to 30.3% at 104 weeks in participants with a starting BMI of 35 or more — 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 has beaten semaglutide in every published head-to-head — though none of those trials used the 7.2 mg semaglutide dose (Wegovy HD) approved in March 2026.
- 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 worth knowing about — dysesthesia, an abnormal skin sensation, in 12.5% at the highest dose in TRIUMPH-1 and up to 20.9% in TRIUMPH-4. High-dose semaglutide (7.2 mg) shows a similar signal; standard doses of semaglutide and tirzepatide show far less.
- Cross-trial comparisons are not head-to-head trials. Different populations, durations and designs mean this ranking is directional, not a precise league table.
CureMed grades this on human trial evidence; animal data never raises a grade.
Retatrutide cost: what the most effective weight-loss drug will cost, and why nobody knows yet
Retatrutide has no price because it is not approved anywhere. Eli Lilly plans to file with the FDA in the first quarter of 2027, so a pharmacy price comes late 2027 at the earliest. The closest guide is Lilly's approved drug Zepbound: $299 to $449 a month in Lilly's self-pay programme. Anything sold online as retatrutide with a price today is not the trial drug.
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, Wegovy HD | GLP-1 receptor agonist | Approved (diabetes and weight management); 7.2 mg dose approved March 2026 |
| 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 | 2,339 | 28.3% (up to 30.3% at 104 weeks, BMI ≥35) | 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 (7.2 mg) | STEP UP, Phase 3 | 1,407 | ~19–21% | 72 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? | 28.3% average weight loss at 80 weeks on the highest dose in TRIUMPH-1 among those who stayed on treatment (25.0% counting everyone randomised; N Engl J Med, September 2026), rising to 30.3% at 104 weeks in participants with a starting BMI of 35 or more; 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 across the programme: 5.1%, 12.3% and 12.5% at 4, 9 and 12 mg in TRIUMPH-1 (0.9% on placebo), and 8.8% at 9 mg and 20.9% at 12 mg in TRIUMPH-4. It is not unique to retatrutide: semaglutide's 7.2 mg dose (Wegovy HD) showed altered skin sensation in roughly 19–22% of participants in STEP UP, against about 5–6% at 2.4 mg, while tirzepatide's label puts dysesthesia below 1%.
- 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. A 7.2 mg dose (Wegovy HD), approved in March 2026, narrows the weight-loss gap to tirzepatide — about 19–21% in STEP UP — at the cost of more skin-sensation side effects.
- 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
I have a vial labeled "RT30" — is that retatrutide?
"RT30" is a vendor-assigned dose code (retatrutide, 30 mg) used by some research-chemical sellers, not a standardized name. Retatrutide itself is a real, closely watched investigational drug — but it is not FDA-approved, and a vial bought this way carries none of the sourcing, purity or dosing controls a prescription product would.
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, with high-dose semaglutide (Wegovy HD 7.2 mg, about 19–21% in STEP UP) now close behind. Retatrutide has shown larger numbers — 28.3% at 80 weeks and up to 30.3% at 104 weeks in TRIUMPH-1 — but it is not FDA-approved and isn't available through a standard prescription.
Retatrutide before and after: what did the trial actually show?
TRIUMPH-1 enrolled 2,339 adults with obesity or overweight and at least one weight-related condition, but no diabetes; they started at an average of 248.5 lb (BMI 40). At 80 weeks, average weight loss was 19.0% on 4 mg, 25.9% on 9 mg and 28.3% on 12 mg, and 45.3% of the 12 mg group lost 30% or more of their body weight. In the 104-week extension, the 532 participants who had started with a BMI of 35 or more and were on 12 mg were down 30.3% on average. The cost: nausea in 42.4% on the top dose, and 11.3% of that group stopped because of side effects, against 4.9% on placebo. Those percentages describe people who stayed on the drug; counting everyone who started, the peer-reviewed paper (New England Journal of Medicine, 29 September 2026) reports 17.6%, 23.7% and 25.0%, against 3.9% on placebo.
Retatrutide vs Mounjaro: which is more effective for weight loss?
On the headline numbers, retatrutide — but compare like with like. Counting everyone who started, retatrutide 12 mg took off 25.0% of body weight at 80 weeks in TRIUMPH-1 (2,339 adults with obesity, no diabetes; New England Journal of Medicine, September 2026), against 20.9% at 72 weeks on tirzepatide 15 mg in SURMOUNT-1 (2,539 adults without diabetes; New England Journal of Medicine, 2022). Among people who stayed on treatment, the figures are 28.3% and 22.5%. Either way those are two different trials with different lengths and different people, not a head-to-head. The first direct comparison — a Lilly trial of retatrutide against tirzepatide in 800 adults with obesity (ClinicalTrials.gov NCT06662383) — is due to complete in December 2026. Tolerability also differs: 11.3% stopped retatrutide 12 mg because of side effects (4.9% on placebo), against 4.3–7.1% on tirzepatide, depending on dose (2.6% on placebo). And only one is a medicine today: tirzepatide has been licensed for weight management since 8 November 2023 (as Mounjaro in the UK, as Zepbound in the US), while retatrutide is not approved anywhere and Lilly plans to file in the first quarter of 2027.
Can you buy retatrutide online?
Not legitimately. The FDA says retatrutide cannot be used in compounding under federal law, and it has warned companies that sell unapproved drugs containing it — including products labelled "for research purposes" or "not for human consumption" — and telehealth firms that market it to consumers (FDA, updated 1 October 2026). In September 2025 six sellers, five in the US and one in Germany, received FDA warning letters. Whatever such a seller ships is not the trial drug: the FDA warns these products may be counterfeit, may contain the wrong or harmful ingredients, or too little, too much or no active ingredient at all.
What are the side effects of retatrutide?
Mostly the stomach, and they rise with the dose. In TRIUMPH-1 (2,339 adults, 80 weeks; New England Journal of Medicine, September 2026), nausea affected 28.6% on 4 mg, 38.4% on 9 mg and 42.4% on 12 mg, against 14.8% on placebo; on the top dose 32.0% had diarrhoea, 26.1% constipation and 25.3% vomiting. Lilly describes these as mostly mild to moderate. About 11% stopped the 12 mg dose because of side effects, against 4% on 4 mg and 5% on placebo. The unusual one is dysesthesia, a burning or tingling feeling in the skin: 5.1%, 12.3% and 12.5% by dose against 0.9% on placebo — Zepbound's label lists it in under 0.5%. Urinary tract infections were slightly more common (7.5–8.7% against 5.3%), and in the phase 2 trial heart rate rose with the dose, peaked at 24 weeks and then declined. Nothing is known beyond two years; a 10,000-person heart and kidney outcomes trial (TRIUMPH-OUTCOMES) is not due to report before 2029.
How much does retatrutide cost?
There is no price, because retatrutide is not approved anywhere: no list price, no insurance price and no pharmacy price. Lilly plans to file with the FDA in the first quarter of 2027, and a standard review takes about 10–12 months, so a pharmacy price comes late 2027 at the earliest. The closest guide is Lilly's approved sibling, Zepbound (tirzepatide): since 1 December 2025, single-dose vials bought through LillyDirect cost $299 a month for 2.5 mg, $399 for 5 mg and $449 for the other doses in Lilly's self-pay programme (reported by Reuters; previously $349–$499). For comparison, Wegovy (semaglutide) has a list price of $1,349.02 a package and a NovoCare self-pay price of $349 a month ($399 for the 7.2 mg HD pen) as of October 2026. Anything sold online as retatrutide with a price today is not the trial drug.
What dose of retatrutide was used in the trials?
This is how the trials dosed it, not a how-to. In the phase 2 trial (338 adults, 48 weeks; New England Journal of Medicine, 2023) retatrutide was a once-weekly injection under the skin, started at 2 mg and raised in steps to 4, 8 and then 12 mg a week; the 12 mg group lost 24.2% of body weight against 2.1% on placebo. Stomach side effects were dose-related, mostly mild to moderate, and fewer with a 2 mg start than a 4 mg start at the same final dose. The phase 3 trial, TRIUMPH-1 (2,339 adults, 80 weeks), used 4, 9 and 12 mg a week: 17.6%, 23.7% and 25.0% of body weight lost when everyone who started is counted (19.0%, 25.9% and 28.3% among those who stayed on treatment), under medical supervision. Nothing sold online as retatrutide is the studied product, and no dose of it is approved for use outside a trial.
Is retatrutide FDA approved?
No. Eli Lilly's July 2026 pipeline update named Q1 2027 as the target for submitting its Biologics License Application. Under the FDA's own performance goals, a standard review of a new biologic is decided within 10 months of the 60-day filing check — about a year from submission — and a priority review within 6 months of it. That puts a standard-review decision around early 2028 and late 2027 only with priority review, and that timeline can slip further. Until then, the two approved injections with the strongest trial results — tirzepatide (Mounjaro, Zepbound) and semaglutide (Wegovy) — are what a prescriber can actually offer.
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.
What is eloralintide, and how much weight did people lose on it?
Eloralintide is Eli Lilly's once-weekly injection that copies amylin, a hormone released with insulin after a meal that signals fullness — so it is not a GLP-1 drug. It is investigational and not approved in any country. In its phase 2 trial (263 adults with obesity or overweight and no type 2 diabetes, 48 weeks; The Lancet, November 2025), people who stayed on the top 9 mg dose lost about 20% of their body weight, against 0.4% on placebo; the lower doses gave about 9% (1 mg), 12% (3 mg) and 18% (6 mg). On 9 mg, 33% reported nausea (14% on placebo) and 43% fatigue (12% on placebo). The phase 3 trial, ENLIGHTEN-1, plans to enrol 1,980 adults and its main data collection is estimated to finish in March 2028 (ClinicalTrials.gov NCT07321886, read 6 October 2026). Promising, but one mid-sized trial is not proof.
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 — one also seen with the 7.2 mg dose of semaglutide — which is exactly the kind of finding ongoing trials exist to characterise before approval.
Keep reading
- Eloralintide: what the first trial shows about Lilly's weekly amylin shot
The amylin drug that is not a GLP-1: weight loss and side effects by dose, and the five phase 3 trials.
- Retatrutide side effects: every number from the trials, by dose
Nausea, dysesthesia, heart rate and who stopped the drug, with the five-minute video.
- Mounjaro vs Ozempic: which works better, and what it costs you
The deep, two-drug head-to-head this page's landscape view builds on.
- Rapamycin for longevity: what the human evidence actually shows
The other major off-label longevity drug category, graded the same way.
- Free stack check
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