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.
Semaglutide is a GLP-1 receptor agonist made by Novo Nordisk and sold as Ozempic (type 2 diabetes), Wegovy (chronic weight management) and Rybelsus (oral tablet for diabetes). It is a fully approved prescription medicine in the UK, US and EU, with large randomised trials showing meaningful weight loss and reduced cardiovascular and kidney events. It is not a research chemical.
Semaglutide sits at grade A; Retatrutide at grade C. On evidence alone, Semaglutide is the safer recommendation. That said, "stronger evidence" doesn't always mean "right for you" — read both pages, then talk to a clinician.
🔬 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.
FDA-approved 2017 and EMA-approved 2018 as Ozempic; oral Rybelsus approved 2019. Indicated alongside diet and exercise to improve glycaemic control in adults with type 2 diabetes.
Wegovy (semaglutide 2.4 mg) is FDA-approved (2021) and EMA-approved (2022) for chronic weight management in adults with obesity, or overweight with at least one weight-related comorbidity. NICE recommends it within specialist services for up to two years.
Approved to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes plus established cardiovascular disease (Ozempic), and — based on SELECT — in adults with obesity or overweight plus established cardiovascular disease without diabetes (Wegovy, 2024).
The safety profile from phase 2 looked broadly similar to other incretin 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.
The commonest side effects are gastrointestinal — nausea, vomiting, diarrhoea, constipation, abdominal pain — typically worst during dose escalation and easing over time. Most are mild to moderate; a minority of patients discontinue because of them. More serious risks on the label include pancreatitis (rare), gallbladder disease (semaglutide modestly increases the rate of cholelithiasis), and acute kidney injury usually mediated by dehydration from vomiting. The FDA label carries a boxed warning for thyroid C-cell tumours based on rodent data; whether this translates to humans is unresolved, but the medicine is contraindicated in anyone with a personal or family history of medullary thyroid carcinoma or MEN 2 syndrome. The EMA confirmed in 2025 that NAION (a rare optic-nerve condition causing sudden vision loss) is a very rare side effect. Not for use in pregnancy or breastfeeding. Counterfeit semaglutide and unregulated compounded versions have caused serious harm — only use a regulated pharmacy supply.
Semaglutide sits at grade A; Retatrutide at grade C. On evidence alone, Semaglutide is the safer recommendation. That said, "stronger evidence" doesn't always mean "right for you" — read both pages, then talk to a clinician.
Pepwyse comparison pages are generated from the same structured data behind each peptide profile. Want a different head-to-head? Use the compare picker or ask Semaglutide directly via the Ask-Peppy button. Not medical advice — see how we grade evidence.