Tirzepatide is a once-weekly injectable medicine made by Eli Lilly, approved for type 2 diabetes (as Mounjaro) and chronic weight management (as Zepbound). It activates two gut-hormone receptors at once — GIP and GLP-1 — and in head-to-head trials produced greater weight loss and A1c reduction than GLP-1-only drugs like semaglutide.
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.
Tirzepatide sits at grade A; Retatrutide at grade C. On evidence alone, Tirzepatide is the safer recommendation. That said, "stronger evidence" doesn't always mean "right for you" — read both pages, then talk to a clinician.
FDA-approved 2022 and EMA-approved 2022 as Mounjaro, as an adjunct to diet and exercise to improve blood-sugar control in adults with type 2 diabetes. The SURPASS programme demonstrated superior A1c reduction versus comparators across five phase-3 trials.
FDA-approved 2023 as Zepbound and authorised in the UK/EU under Mounjaro, for adults with obesity (BMI ≥30) or overweight with a weight-related comorbidity. SURMOUNT-1 showed mean weight reductions up to 22.5% at 72 weeks.
FDA-approved in 2024 (as Zepbound) for moderate-to-severe OSA in adults with obesity, on the basis of the SURMOUNT-OSA trials, which showed clinically meaningful reductions in apnoea-hypopnoea index.
🔬 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.
The most common side effects are gastrointestinal: nausea, diarrhoea, constipation, vomiting and reduced appetite — usually mildest during dose titration and easing over time. Serious but less common risks flagged on the FDA label include pancreatitis, gallbladder disease, acute kidney injury (often via dehydration), and severe hypersensitivity reactions. Tirzepatide carries a boxed warning for thyroid C-cell tumours based on rodent data and is contraindicated in people with a personal or family history of medullary thyroid carcinoma or MEN-2 syndrome. It is not recommended in pregnancy. Long-term safety beyond a few years is still being characterised.
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.
Tirzepatide sits at grade A; Retatrutide at grade C. On evidence alone, Tirzepatide 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 Tirzepatide directly via the Ask-Peppy button. Not medical advice — see how we grade evidence.