Retatrutide vs semaglutide: in its phase 3 obesity trial, investigational retatrutide produced an average 25.0% weight loss at 80 weeks on the 12 mg dose, compared with 14.9% at 68 weeks for semaglutide 2.4 mg (Wegovy) in its main trial.[1][2] The drugs have not been compared directly, and only semaglutide is approved: Lilly plans to submit retatrutide to the FDA in the first quarter of 2027.[3]
Read the retatrutide profile for the full trial history, and our retatrutide dosage guide for the doses tested.
Retatrutide vs semaglutide at a glance
| Retatrutide | Semaglutide | |
|---|---|---|
| Status | Investigational, not approved[3] | Approved (Wegovy, Ozempic, Rybelsus)[4] |
| Maker | Eli Lilly | Novo Nordisk |
| Receptors | GLP-1, GIP and glucagon[5] | GLP-1[4] |
| Dosing | Weekly injection in trials[1] | Weekly injection or daily pill[4] |
| Top dose studied/approved | 12 mg weekly[1] | 7.2 mg weekly (Wegovy)[4] |
| Main obesity trial | −25.0% at 80 weeks (TRIUMPH-1)[1] | −14.9% at 68 weeks (STEP 1)[2] |
| Higher-dose result | — | −18.7% at 72 weeks (7.2 mg, STEP UP)[6] |
| Heart-outcome data | None reported yet | Lowered heart events in SELECT[11] |
How they work
Semaglutide copies GLP-1, a gut hormone that reduces appetite, slows stomach emptying and boosts insulin after meals.[4]
Retatrutide is a “triple agonist”. It switches on three receptors in one molecule: GLP-1, GIP (a second gut hormone involved in insulin release) and glucagon. In lab studies, the GLP-1 and GIP actions reduced food intake, and the glucagon action added an increase in energy use.[5] Tirzepatide, by comparison, acts on two of these receptors (GIP and GLP-1); see retatrutide vs tirzepatide.
Weight loss: TRIUMPH vs STEP
| Trial | Drug and dose | Weeks | Weight change | Placebo |
|---|---|---|---|---|
| TRIUMPH-1 | Retatrutide 4 / 9 / 12 mg | 80 | −17.6% / −23.7% / −25.0%[1] | −3.9% |
| Phase 2 | Retatrutide 12 mg | 48 | −24.2%[7] | −2.1% |
| STEP 1 | Semaglutide 2.4 mg | 68 | −14.9%[2] | −2.4% |
| STEP UP | Semaglutide 7.2 mg | 72 | −18.7%[6] | −3.9% |
| TRIUMPH-2 (type 2 diabetes) | Retatrutide 12 mg | 80 | −18.8%[8] | −5.1% |
| STEP 2 (type 2 diabetes) | Semaglutide 2.4 mg | 68 | −9.6%[9] | −3.4% |
All figures count everyone who was randomized, including people who stopped treatment. Lilly’s earlier topline report for TRIUMPH-1 also gave higher “on-treatment” figures, such as 28.3% on 12 mg.[10]
Type 2 diabetes
Semaglutide is already approved for type 2 diabetes as Ozempic and Rybelsus.[4] Retatrutide has completed a phase 3 diabetes trial: in TRANSCEND-T2D-1, 537 adults with early type 2 diabetes saw HbA1c fall by 1.69 to 1.94 points over 40 weeks versus 0.81 on placebo, with weight loss of 11.5% to 15.3%.[16] For comparison, in STEP 2 semaglutide 2.4 mg lowered weight by 9.6% in people with type 2 diabetes and overweight over 68 weeks.[9] Again, these are different trials with different people.
Liver fat
- Retatrutide: in a 98-person substudy of people with fatty liver disease, liver fat fell by about 81% to 82% on the 8 and 12 mg doses after 24 weeks, and most reached normal liver fat levels.[17]
- Semaglutide: in the phase 3 ESSENCE trial in people with MASH (an inflamed, scarring form of fatty liver disease), 62.9% on semaglutide 2.4 mg had their steatohepatitis resolve without worsening scarring, versus 34.3% on placebo.[18] That trial supported Wegovy’s accelerated approval for MASH.[4]
The retatrutide result measured fat in the liver on scans; the semaglutide result measured tissue changes on liver biopsy, so they answer different questions.
Other conditions studied
- Knee osteoarthritis: in 574 TRIUMPH-1 participants with knee arthritis, retatrutide reduced pain scores more than placebo.[1]
- Sleep apnea: in 243 participants, breathing interruptions fell by about 23 to 34 events per hour on retatrutide versus about 10 on placebo.[1]
- Heart: semaglutide lowered heart attack, stroke and cardiovascular death from 8.0% to 6.5% in 17,604 adults with heart disease and overweight in SELECT.[11] Retatrutide has no completed heart-outcomes trial.
Side effects compared
Both cause mainly stomach side effects that rise with dose.
| Side effect | Retatrutide 12 mg (TRIUMPH-1) | Semaglutide 2.4 mg (STEP UP) | Semaglutide 7.2 mg (STEP UP) |
|---|---|---|---|
| Nausea | 42.4%[10] | — | — |
| Any stomach side effect | — | 61.2%[6] | 70.8%[6] |
| Dysesthesia (abnormal skin sensation) | 5.1% to 12.5% across doses[10] | 6.0%[6] | 22.9%[6] |
| Stopped for side effects | 11.3%[10] | — | — |
- Semaglutide 2.4 mg (STEP 1): 4.5% stopped because of stomach side effects, versus 0.8% on placebo.[2]
- Retatrutide in diabetes (TRIUMPH-2): low blood pressure (up to 6%) and dysesthesia (up to 7%) were more common than with placebo.[8]
- Heart rate: in the retatrutide phase 2 trial, heart rate rose with dose, peaked at 24 weeks and then declined.[7]
- Thyroid warning: semaglutide carries a boxed warning about thyroid C-cell tumors in rodents.[4] Retatrutide has no label yet.
Can you get retatrutide?
Not as a prescription. It is available only in clinical trials and through Lilly’s pre-approval expanded access program for a narrow group of adults with severe obesity and serious complications.[13] FDA has warned companies selling retatrutide labeled “for research purposes” for human use, and says retatrutide cannot be used in compounding.[15] Anything sold online as retatrutide is not the product tested in the trials.
Semaglutide, by contrast, is available as Wegovy injections and tablets for weight management, and as Ozempic and Rybelsus for type 2 diabetes.[4]
What comes next
Lilly said in August 2026 that its clinical data were complete to support registrations for obesity, sleep apnea and knee osteoarthritis pain, with a US submission planned for the first quarter of 2027.[3] A head-to-head trial against tirzepatide (TRIUMPH-5) is under way.[14] No head-to-head trial against semaglutide has been published.
What this means for you today
If you need treatment now, semaglutide is a real prescription option with years of safety data, heart-outcome evidence and several forms (weekly injection, daily pill), while retatrutide is not available outside research.[4][11] If retatrutide is approved, its label will set the doses, warnings and who it is for, which may differ from the trials. People who take semaglutide and are curious about retatrutide can ask their clinician whether a clinical trial is recruiting nearby, and should not stop an approved treatment to wait for it.
Until retatrutide is approved, semaglutide and tirzepatide remain the most effective approved options. Compare those two in semaglutide vs tirzepatide.
