Retatrutide (LY3437943) is an investigational triple receptor agonist from Eli Lilly that activates the GIP, GLP-1 and glucagon receptors. In a phase 2 trial it produced roughly 24% weight loss at 48 weeks at the top dose, the largest seen in an obesity drug to date. It is not approved anywhere; phase 3 trials are ongoing.
Survodutide (BI 456906) is an investigational once-weekly dual glucagon (GCGR) and GLP-1 receptor agonist from Boehringer Ingelheim and Zealand Pharma. By hitting both receptors it aims to cut appetite and burn more energy, and it shows promising phase 2 results in obesity and liver disease (MASH). It is not approved anywhere; access is via clinical trial only.
Both peptides share an evidence grade of C. The right choice depends less on the data and more on what you're trying to do, Retatrutide for obesity, Survodutide for obesity / weight management.
🔬 Phase 2 trial (n=338) reported ~24% mean weight loss at 48 weeks on the 12 mg dose, the largest reduction reported for any obesity drug at that point. Phase 3 (TRIUMPH programme) is ongoing; results not yet read out.
🔬 Phase 2 trial showed substantial reductions in HbA1c and body weight in adults with T2D. Phase 3 data still pending; not approved for diabetes.
🔬 Phase 2 substudy reported large reductions in liver fat. Promising mechanistic signal; trials in MASH are ongoing.
🔬 A phase 2 dose-finding trial in adults with overweight or obesity (le Roux et al., The Lancet, 2024; ~387 participants) reported dose-dependent mean weight loss of roughly 15% at 46 weeks on the highest doses, with a clear dose-response. Promising, but phase 2 — the pivotal phase 3 obesity programme is ongoing and survodutide is not approved.
🔬 A phase 2 trial in biopsy-confirmed MASH (Sanyal et al., New England Journal of Medicine, 2024) reported that up to ~83% of participants on survodutide achieved improvement in MASH versus ~18% on placebo, with reductions in liver fat. This is among the most notable phase 2 MASH signals to date, but it is a single phase 2 trial; confirmatory phase 3 work is required.
🔬 In the same phase 2 MASH trial, more participants on survodutide than placebo showed improvement in liver fibrosis without worsening of MASH. The fibrosis signal is encouraging but secondary and underpowered for firm conclusions; fibrosis endpoints are the hard test that phase 3 must confirm.
The safety profile from phase 2 looked broadly similar to other [incretin](/glossary "Incretin: Gut hormones (like GLP-1 and GIP) released after eating that boost insulin and curb appetite. The hormone family behind the new weight-loss drugs.") drugs: mainly gastrointestinal, nausea, vomiting, diarrhoea, constipation, most often during dose escalation. The glucagon component introduces a theoretical risk of increased heart rate and changes in glucose handling that needs longer-term data to characterise properly. Because the published follow-up is short and the population studied is selective, rare or long-latency adverse events have not been ruled out. Pregnancy, breastfeeding, personal or family history of medullary thyroid cancer or MEN-2, severe gastrointestinal disease, and pancreatitis history are typical exclusions in trials of this class. Quality and content of any non-trial "retatrutide" is unknown and unverifiable.
In phase 2 trials the most common adverse events were gastrointestinal — nausea, vomiting, diarrhoea and constipation — typically worst during dose escalation and easing afterwards, as with the wider GLP-1 class. The distinctive safety consideration is the glucagon receptor arm: glucagon agonism can increase heart rate and, by raising blood sugar, partially offset glycaemic benefit, which is one reason trials titrate the dose slowly. Injection-site reactions are reported. Long-term cardiovascular safety, effects in people with established heart disease, and durability beyond the phase 2 windows are not yet characterised. Typical trial exclusions for this class include pregnancy and breastfeeding, personal or family history of medullary thyroid cancer or MEN-2, active pancreatitis and severe gastrointestinal disease. The quality of any non-trial 'survodutide' bought online is entirely unknown.
Both peptides share an evidence grade of C. The right choice depends less on the data and more on what you're trying to do, Retatrutide for obesity, Survodutide for obesity / weight management.
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