Retatrutide vs Survodutide: Triple Agonist vs Dual Agonist
Retatrutide and survodutide are both next-generation obesity drugs that share an unusual feature: glucagon receptor agonism. Neither semaglutide (Ozempic/Wegovy) nor tirzepatide (Mounjaro/Zepbound) targets the glucagon receptor. These two drugs do — and that shared element is what makes this comparison interesting.
The key difference is what else they target. Retatrutide is a triple agonist (GLP-1 + GIP + glucagon), developed by Eli Lilly. Survodutide is a dual agonist (GLP-1 + glucagon), developed by Boehringer Ingelheim and Zealand Pharma. Retatrutide includes GIP agonism on top of the two receptors survodutide targets.
Neither drug is FDA-approved. Both are in Phase 3 clinical trials. No head-to-head trial has compared them directly, and the Phase 2 data discussed below comes from different trials with different designs, populations, and durations.
Side-by-Side Comparison
| Retatrutide | Survodutide | |
|---|---|---|
| Mechanism | GLP-1 + GIP + Glucagon (triple agonist) | GLP-1 + Glucagon (dual agonist) |
| Development code | LY3437943 | BI 456906 |
| Manufacturer | Eli Lilly | Boehringer Ingelheim / Zealand Pharma |
| FDA status | Not approved — Phase 3 (TRIUMPH program) | Not approved — Phase 3 ongoing |
| Dosing | Once weekly injection | Once weekly injection |
| Max dose tested | 12 mg | 4.8 mg |
| Max weight loss (Phase 2) | -24.2% at 48 weeks | -14.9% at 46 weeks |
| Max weight loss (Phase 3) | -28.7% at 68 weeks (TRIUMPH-4) | Pending |
| Glucagon agonism | Yes | Yes |
| GIP agonism | Yes | No |
| MASH/MASLD studies | Yes (TRIUMPH program) | Yes |
| Availability | Clinical trials only | Clinical trials only |
How the Mechanisms Differ
Both retatrutide and survodutide include glucagon receptor activation, which sets them apart from the current generation of approved weight loss drugs. The glucagon receptor drives increased energy expenditure through thermogenesis and fat oxidation — meaning these drugs do not rely solely on appetite suppression.
Survodutide: GLP-1 + Glucagon
Survodutide combines GLP-1 agonism (the same mechanism behind Ozempic and Wegovy) with glucagon agonism. The GLP-1 component reduces appetite, slows gastric emptying, and improves insulin secretion. The glucagon component increases energy expenditure and promotes fat breakdown, particularly in the liver.
This dual approach is similar to mazdutide (developed by Innovent Biologics), which also targets GLP-1 and glucagon. Survodutide does not include GIP agonism.
Retatrutide: GLP-1 + GIP + Glucagon
Retatrutide includes everything survodutide does — GLP-1 and glucagon agonism — and adds GIP (glucose-dependent insulinotropic polypeptide) as a third target. GIP further enhances insulin secretion and may have additional effects on fat metabolism. The inclusion of GIP is the same addition that differentiates tirzepatide from semaglutide, and it appears to contribute to greater overall weight loss.
In short: survodutide combines appetite suppression with increased energy expenditure. Retatrutide does the same, with an additional metabolic pathway through GIP.
For a deeper explanation of each receptor, see What Is Retatrutide (GLP-3)?.
Weight Loss Comparison
Phase 2 Results
Both drugs have published Phase 2 weight loss data, but the trial designs differ in ways that matter.
| Drug | Trial | Duration | Participants | Max Weight Loss (ITT) |
|---|---|---|---|---|
| Retatrutide 12 mg | Phase 2 (NEJM, NCT04881760) | 48 weeks | 338 | -24.2% |
| Survodutide 4.8 mg | Phase 2 (Lancet Diabetes Endocrinol, NCT04667377) | 46 weeks | 386 | -14.9% |
Survodutide Phase 2 Results by Dose
| Dose | Weight Loss (%) |
|---|---|
| 0.6 mg | -6.2% |
| 2.4 mg | -12.5% |
| 3.6 mg | -13.2% |
| 4.8 mg | -14.9% |
| Placebo | -2.8% |
In the survodutide trial, participants who completed the full treatment course on the 4.8 mg dose (the "actual treatment" analysis) achieved nearly -19% weight loss — and weight loss had not plateaued at 46 weeks, suggesting the final ceiling may be higher with longer treatment or higher doses. Up to 40% of participants on the highest doses achieved 20% or more weight loss.
Retatrutide Phase 3 Results
Retatrutide's Phase 3 TRIUMPH-4 trial extended treatment to 68 weeks and reported -28.7% weight loss at the 12 mg dose. This is the largest weight loss result ever reported for an anti-obesity medication in a clinical trial. For full Phase 3 data, see Clinical Trials & Results.
Why These Numbers Are Not Directly Comparable
This comparison comes with significant caveats:
- Different trial designs: The survodutide Phase 2 trial used a 20-week dose escalation followed by 26 weeks of maintenance. The retatrutide Phase 2 trial used a different titration schedule.
- Different populations: Both trials enrolled adults with BMI of 27 or higher, but exclusion criteria, baseline characteristics, and comorbidity profiles differed.
- Different durations: 46 weeks (survodutide) vs 48 weeks (retatrutide Phase 2) vs 68 weeks (retatrutide Phase 3).
- Different trial phases: Retatrutide has Phase 3 data; survodutide Phase 3 results are pending.
- No head-to-head trial: The only reliable way to compare two drugs is in a randomized controlled trial where participants are assigned to each drug under identical conditions. That trial does not exist for these two drugs.
The general trend — the triple agonist produced more weight loss than the dual agonist — is directionally consistent with the hypothesis that adding GIP provides additional benefit. But the precise magnitude of the difference cannot be determined from cross-trial comparisons.
Tolerability and Discontinuation
Both drugs produce gastrointestinal side effects common to the GLP-1 agonist class: nausea, vomiting, diarrhea, and constipation. However, the survodutide Phase 2 trial had a notably higher discontinuation rate.
| Retatrutide (Phase 2) | Survodutide (Phase 2) | |
|---|---|---|
| Common side effects | Nausea, diarrhea, vomiting, constipation | Nausea, diarrhea, vomiting, constipation |
| Discontinuation due to AEs | Lower (varied by dose) | 24.6% (vs 3.9% placebo) |
| Notable signal | Dysesthesia (tingling/burning) | GI events during rapid dose escalation |
The survodutide trial's 24.6% discontinuation rate due to adverse events is high compared to both retatrutide's Phase 2 data and the broader incretin drug class. However, context matters: the survodutide trial used a relatively rapid dose escalation over 20 weeks, which likely contributed to GI intolerance. Slower dose titration in Phase 3 trials may improve this number.
Retatrutide's Phase 2 trial reported a distinct side effect — dysesthesia (tingling, burning, or prickling sensations on the skin) — that is not commonly seen with survodutide, semaglutide, or tirzepatide. This appears related to the glucagon receptor and is being monitored in Phase 3 trials.
For more on retatrutide's safety profile, see Side Effects & Safety.
Liver Fat and MASH
Both drugs are being studied for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD). This is one of the most promising areas for glucagon-containing agonists.
Glucagon receptor activation directly promotes fat oxidation in the liver, reducing both fat accumulation and inflammation. This makes both survodutide and retatrutide strong candidates for liver disease — a therapeutic area where current treatment options are extremely limited.
Retatrutide showed an 81-86% reduction in liver fat in its Phase 2 trial at the 12 mg dose — a dramatic result that far exceeds what semaglutide or tirzepatide have achieved. The Phase 3 TRIUMPH program includes a dedicated MASH trial.
Survodutide is also being actively studied in MASH/MASLD, with dedicated trials underway. Published Phase 2 data has demonstrated significant liver fat reductions, and the Boehringer Ingelheim MASH program is a major part of survodutide's development strategy.
The shared glucagon mechanism makes both drugs potentially important for liver disease, regardless of which produces more weight loss overall.
Development Status
| Milestone | Retatrutide | Survodutide |
|---|---|---|
| Phase 1 | Completed | Completed |
| Phase 2 | Completed (published 2023) | Completed (published 2024) |
| Phase 3 | Ongoing (TRIUMPH program, 5+ trials) | Ongoing |
| First Phase 3 readout | TRIUMPH-4 (December 2025) | Pending |
| Expected FDA filing | Late 2026 / early 2027 | TBD |
| Expected approval | 2027 (earliest) | TBD |
Retatrutide is further along in development. The TRIUMPH Phase 3 program has already produced its first readout (TRIUMPH-4), and Eli Lilly has indicated it is on track for an NDA filing. Survodutide's Phase 3 program is underway, but top-line results have not yet been reported.
For retatrutide's full regulatory timeline, see FDA Approval Timeline.
Frequently Asked Questions
Is retatrutide better than survodutide?
Retatrutide has produced larger weight loss numbers in clinical trials (up to -28.7% vs -14.9% in Phase 2 ITT analyses). However, "better" depends on context. These results come from different trials with different designs, and survodutide's weight loss had not plateaued at 46 weeks. Survodutide may also have advantages in specific populations or for specific conditions like MASH. No head-to-head trial has compared the two drugs, so a definitive answer is not yet possible.
Why do both drugs include glucagon?
Glucagon receptor agonism increases energy expenditure — meaning your body burns more calories at rest. It also promotes fat oxidation, particularly in the liver. This makes glucagon a valuable addition to the GLP-1 foundation because it attacks obesity from both sides of the energy balance equation: reduced intake (GLP-1) and increased expenditure (glucagon). Both drug developers recognized this potential, but they took different approaches — survodutide paired glucagon with GLP-1 alone, while retatrutide added GIP as a third target.
What does survodutide have that retatrutide does not?
In terms of receptor targets, nothing — retatrutide targets all three receptors that survodutide targets (GLP-1 and glucagon) plus GIP. However, the ratio of glucagon to GLP-1 activity may differ between the two drugs, which could produce different metabolic profiles. Survodutide may have a relatively stronger glucagon signal, which could be advantageous for liver fat reduction specifically. These nuances will only become clear with more Phase 3 data and, ideally, head-to-head comparisons.
Will either drug be available soon?
Neither drug is FDA-approved. Retatrutide is expected to be the first to market, with a potential FDA approval in 2027. Survodutide's timeline is less defined. Both drugs are currently available only through clinical trial enrollment. For retatrutide trials, visit ClinicalTrials.gov.
How do these drugs compare to Ozempic and Mounjaro?
Both retatrutide and survodutide have produced larger weight loss results in Phase 2 trials than semaglutide (Ozempic/Wegovy). Retatrutide's Phase 3 results also exceed tirzepatide's (Mounjaro/Zepbound). However, semaglutide and tirzepatide are both FDA-approved and available now. For a full comparison with approved drugs, see Retatrutide vs Mounjaro vs Ozempic.
Sources
- Jastreboff, A.M., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. DOI: 10.1056/NEJMoa2301972
- Le Roux, C.W., et al. (2024). Survodutide for the treatment of obesity: a Phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. The Lancet Diabetes & Endocrinology. NCT04667377
- Eli Lilly and Company. (2025). Lilly's retatrutide achieved significant weight loss and pain relief in adults with obesity and knee osteoarthritis. Press release.
- ClinicalTrials.gov: NCT04881760 (retatrutide Phase 2), NCT04667377 (survodutide Phase 2)
Medical Disclaimer
The content on glp3.wiki is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. Retatrutide and survodutide are both investigational drugs that have not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory agency.
Do not use this information to make decisions about your health without consulting a qualified healthcare provider. The clinical trial data cited on this page reflects results from controlled research settings and may not reflect real-world outcomes.
If you are considering weight loss medication, talk to your doctor about currently approved options. For information about enrolling in clinical trials, visit ClinicalTrials.gov.
This site is not affiliated with Eli Lilly and Company, Boehringer Ingelheim, Zealand Pharma, or any pharmaceutical manufacturer.
Sources
- Retatrutide Phase 2 trial
NEJM
- Survodutide Phase 2 trial
ClinicalTrials.gov
Related reading
Retatrutide vs Mounjaro vs Ozempic
How the three generations of weight loss drugs compare — single, dual, and triple agonists.
What Is Retatrutide (GLP-3)?
The world's first triple agonist weight loss drug — how it works, what the trials show, and why people call it GLP-3.
Retatrutide Clinical Trials & Results
Living tracker of all retatrutide trials — Phase 1 through the TRIUMPH Phase 3 program.