{ "_meta": { "compiled": "2026-10-08", "method": "Every value was read from a source opened on the compile date. emc SmPC pages were readable only up to roughly the first 100,000 characters, so SmPC sections 5.2 to 10 were out of reach for Mounjaro, Wegovy injection and Foundayo. Storage for those comes from the emc patient leaflets. NEJM, JAMA and Lancet full texts were blocked, so trial numbers come from the journal abstracts (via Europe PMC records), the UK SmPC tables, the FDA label or the sponsor press release, as stated per item.", "estimand_note": "Treatment-regimen (also called treatment policy) counts everyone randomised whether or not they stayed on the medicine. Efficacy (also called trial product) estimates the effect if people stayed on the medicine. Efficacy figures are always higher. UK SmPC tables for Mounjaro and Foundayo use the efficacy estimand.", "publisher": "Aero Clinic", "url": "https://www.cagri.co.uk/clinical-evidence", "checked": "2026-10-15", "note": "Trial figures are treatment-regimen averages unless stated. Cite the trial and this page." }, "medicines": { "mounjaro": { "generic": "tirzepatide", "class": "Dual GIP and GLP-1 receptor agonist", "form": "Solution for subcutaneous injection in a pre-filled multi-dose KwikPen", "frequency": "Once weekly", "uk_dose_steps": [ { "dose": "2.5 mg", "min_weeks": 4, "role": "starter" }, { "dose": "5 mg", "min_weeks": 4, "role": "maintenance or step" }, { "dose": "7.5 mg", "min_weeks": 4, "role": "step" }, { "dose": "10 mg", "min_weeks": 4, "role": "maintenance or step" }, { "dose": "12.5 mg", "min_weeks": 4, "role": "step" }, { "dose": "15 mg", "min_weeks": null, "role": "maintenance, maximum" } ], "maintenance_doses": "5 mg, 10 mg and 15 mg once weekly (adults)", "max_dose": "15 mg once weekly", "missed_dose_rule": "Take the missed dose as soon as possible within 4 days of the missed dose. If more than 4 days have passed, skip the dose and take the next one on the usual day. Leave at least 3 days between two doses. Do not take a double dose.", "storage": "Store in a refrigerator at 2 to 8 degrees C. Do not freeze, and do not use a pen that has been frozen. The KwikPen can be kept unrefrigerated at up to 30 degrees C for up to 30 days after first use, then the pen must be discarded.", "half_life": "Approximately 5 days", "key_trial": { "name": "SURMOUNT-1", "population": "Adults with BMI 30 or more, or 27 or more with at least one weight-related complication, without diabetes. Mean baseline weight 104.8 kg, mean BMI 38.0.", "n": 2539, "duration_weeks": 72, "dose": "15 mg", "mean_loss_treatment_regimen_pct": 20.9, "mean_loss_efficacy_pct": 22.5, "placebo_loss_pct": 3.1, "placebo_loss_efficacy_pct": 2.4, "pct_reaching_5": 90.9, "pct_reaching_10": 83.5, "pct_reaching_15": 70.6, "pct_reaching_20": 56.7, "placebo_pct_reaching": { "5": 34.5, "10": 18.8, "15": 8.8, "20": 3.1 }, "thresholds_estimand": "treatment-regimen (FDA Zepbound label Study 1, matches NEJM abstract 91% and 57%)", "efficacy_estimand_thresholds_15mg": { "5": 96.3, "10": 90.1, "15": 78.2, "20": 62.9, "placebo": { "5": 27.9, "10": 13.5, "15": 6.0, "20": 1.3 }, "source": "UK SmPC Table 9" }, "by_dose": { "5 mg": { "treatment_regimen_pct": 15.0, "efficacy_pct": 16.0 }, "10 mg": { "treatment_regimen_pct": 19.5, "efficacy_pct": 21.4 }, "15 mg": { "treatment_regimen_pct": 20.9, "efficacy_pct": 22.5 } }, "discontinued_due_to_adverse_events_pct": { "5 mg": 4.3, "10 mg": 7.1, "15 mg": 6.2, "placebo": 2.6 }, "citation": "Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205-216", "url": "https://doi.org/10.1056/NEJMoa2206038" }, "other_trials": [ { "name": "SURMOUNT-4 (withdrawal)", "finding": "After a 36-week tirzepatide lead-in with 20.9% mean weight loss, 670 adults were randomised. Over the next 52 weeks weight changed by -5.5% with continued tirzepatide and +14.0% with placebo. Total loss from week 0 to 88 was 25.3% versus 9.9%. 89.5% versus 16.6% kept at least 80% of the lead-in loss.", "url": "https://doi.org/10.1001/jama.2023.24945" }, { "name": "SURMOUNT-5 (head to head)", "finding": "In 751 adults with obesity without type 2 diabetes, mean weight change at 72 weeks was -20.2% with tirzepatide (10 or 15 mg) and -13.7% with semaglutide (1.7 or 2.4 mg). Waist change was -18.4 cm versus -13.0 cm. Open-label trial.", "url": "https://doi.org/10.1056/NEJMoa2416394" }, { "name": "SURMOUNT-OSA", "finding": "In adults with moderate to severe obstructive sleep apnoea and obesity, AHI fell by 25.3 events per hour with tirzepatide versus 5.3 with placebo in people not using PAP, and by 29.3 versus 5.5 in people using PAP, at 52 weeks.", "url": "https://doi.org/10.1056/NEJMoa2404881" } ], "common_side_effects": [ { "effect": "nausea", "rate_pct": 28.0, "placebo_pct": 8.5, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (UK SmPC 4.8)" }, { "effect": "diarrhoea", "rate_pct": 22.5, "placebo_pct": 7.8, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (UK SmPC 4.8)" }, { "effect": "vomiting", "rate_pct": 13, "placebo_pct": 2, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (FDA Zepbound label Table 1, whole numbers)" }, { "effect": "constipation", "rate_pct": 11, "placebo_pct": 5, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (FDA Zepbound label Table 1, whole numbers)" }, { "effect": "abdominal pain", "rate_pct": 10, "placebo_pct": 5, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (FDA Zepbound label Table 1)" }, { "effect": "dyspepsia", "rate_pct": 10, "placebo_pct": 4, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (FDA Zepbound label Table 1)" }, { "effect": "injection site reactions", "rate_pct": 8, "placebo_pct": 2, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (FDA Zepbound label Table 1)" }, { "effect": "fatigue", "rate_pct": 7, "placebo_pct": 3, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (FDA Zepbound label Table 1)" }, { "effect": "hair loss", "rate_pct": 5, "placebo_pct": 1, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (FDA Zepbound label Table 1)" }, { "effect": "any gastrointestinal disorder", "rate_pct": 55.6, "placebo_pct": 29.7, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (UK SmPC 4.8)" }, { "effect": "stopped treatment because of a gastrointestinal event", "rate_pct": 4.3, "placebo_pct": 0.5, "dose": "15 mg", "source_trial": "SURMOUNT-1 and SURMOUNT-2 pooled (UK SmPC 4.8)" } ], "other_evidence": [ "Sleep apnoea trial: SURMOUNT-OSA, 469 adults, 52 weeks. AHI change -25.3 versus -5.3 events per hour (no PAP) and -29.3 versus -5.5 (on PAP). FDA label: AHI fell 50.7% and 58.7% with tirzepatide versus 3.0% and 2.5% with placebo, and 42.2% and 50.2% reached remission or mild non-symptomatic OSA versus 15.9% and 14.3%.", "Sleep apnoea licence: the UK SmPC section 4.1 lists type 2 diabetes and weight management only. Obstructive sleep apnoea appears as an example weight-related comorbidity and as trial data in section 5.1, not as a separate indication. The EMA declined a separate OSA indication on 13 December 2024 because the weight management indication already covers these patients. The US FDA label does carry an OSA indication.", "UK SmPC also lists paediatric type 2 diabetes use from age 10 (maximum 10 mg). The weight management indication is adults only." ], "contraception_note": "Tirzepatide can make oral contraceptives less effective. The SmPC advises switching to a non-oral method or adding a barrier method for 4 weeks after starting and for 4 weeks after each dose increase.", "pregnancy_washout": "Not recommended in pregnancy. Stop at least 1 month before a planned pregnancy.", "sources": [ { "t": "Mounjaro KwikPen SmPC (emc, last updated 8 Sep 2026)", "u": "https://www.medicines.org.uk/emc/product/15481/smpc" }, { "t": "Mounjaro KwikPen patient leaflet (emc)", "u": "https://www.medicines.org.uk/emc/product/15481/pil" }, { "t": "SURMOUNT-1, NEJM 2022", "u": "https://doi.org/10.1056/NEJMoa2206038" }, { "t": "SURMOUNT-4, JAMA 2024", "u": "https://doi.org/10.1001/jama.2023.24945" }, { "t": "SURMOUNT-5, NEJM 2025", "u": "https://doi.org/10.1056/NEJMoa2416394" }, { "t": "SURMOUNT-OSA, NEJM 2024", "u": "https://doi.org/10.1056/NEJMoa2404881" }, { "t": "Zepbound US prescribing information (FDA label)", "u": "https://pi.lilly.com/us/zepbound-uspi.pdf" }, { "t": "MHRA press release, weight management authorisation, 8 Nov 2023", "u": "https://www.gov.uk/government/news/mhra-authorises-diabetes-drug-mounjaro-tirzepatide-for-weight-management-and-weight-loss" }, { "t": "EMA Q&A on Mounjaro and obstructive sleep apnoea, 13 Dec 2024", "u": "https://www.ema.europa.eu/en/documents/medicine-qa/questions-answers-outcome-assessment-use-mounjaro-treatment-obstructive-sleep-apnoea_en.pdf" } ], "notes": "SmPC sections 5.2 to 10 could not be read in full. Half-life (about 5 days) was returned from the SmPC page. Storage comes from the emc patient leaflet. Single-trial SURMOUNT-1 side effect rates by dose (NEJM Table 3) could not be opened, so rates are the pooled SURMOUNT-1 and SURMOUNT-2 figures from the UK SmPC and the FDA label. SmPC quotes 4 weeks minimum per step. No minimum applies at 15 mg, so min_weeks is null there. SURMOUNT-4 participant counts differ between sources: JAMA reports 783 enrolled and 670 randomised (335 per arm), the emc SmPC text reads 782 patients and 355 continuing tirzepatide. Use the JAMA figures. SURMOUNT-OSA percentage weight change and SURMOUNT-5 threshold percentages were not verified and are left out." }, "wegovy": { "generic": "semaglutide", "class": "GLP-1 receptor agonist", "form": "Solution for subcutaneous injection in a pre-filled multi-dose FlexTouch pen", "frequency": "Once weekly", "uk_dose_steps": [ { "dose": "0.25 mg", "min_weeks": 4, "role": "starter" }, { "dose": "0.5 mg", "min_weeks": 4, "role": "step" }, { "dose": "1 mg", "min_weeks": 4, "role": "step" }, { "dose": "1.7 mg", "min_weeks": 4, "role": "step" }, { "dose": "2.4 mg", "min_weeks": 4, "role": "maintenance (4 weeks minimum applies only before moving to 7.2 mg)" }, { "dose": "7.2 mg", "min_weeks": null, "role": "optional higher dose for adults with BMI 30 or more only" } ], "maintenance_doses": "2.4 mg once weekly for all indications. Adults with obesity (BMI 30 or more) who need more weight loss can move to 7.2 mg once weekly after at least 4 weeks on 2.4 mg.", "max_dose": "7.2 mg once weekly for adults with obesity. 2.4 mg once weekly for adults with BMI 27 to under 30, for cardiovascular risk reduction and for adolescents aged 12 and over.", "missed_dose_rule": "Take the missed dose as soon as possible within 5 days of the missed dose. If more than 5 days have passed, skip the dose and take the next one on the usual day. Do not take a double dose.", "storage": "Before first use store in a refrigerator at 2 to 8 degrees C, away from the cooling element. After first use the pen can be kept for 6 weeks below 30 degrees C or in a refrigerator. Keep the cap on to protect from light. Do not freeze, and do not use a pen that has been frozen.", "half_life": "Approximately 1 week", "key_trial": { "name": "STEP 1", "population": "Adults with BMI 30 or more, or 27 or more with at least one weight-related condition, without diabetes", "n": 1961, "duration_weeks": 68, "dose": "2.4 mg", "mean_loss_treatment_regimen_pct": 14.9, "mean_loss_efficacy_pct": null, "placebo_loss_pct": 2.4, "mean_loss_kg": 15.3, "placebo_loss_kg": 2.6, "pct_reaching_5": 86.4, "pct_reaching_10": 69.1, "pct_reaching_15": 50.5, "pct_reaching_20": null, "placebo_pct_reaching": { "5": 31.5, "10": 12.0, "15": 4.9, "20": null }, "thresholds_estimand": "NEJM abstract, observed in-trial data", "smpc_thresholds": { "5": 83.5, "10": 66.1, "15": 47.9, "20": 30.2, "placebo": { "5": 31.1, "10": 12.0, "15": 4.8, "20": 1.7 }, "source": "UK SmPC STEP 1 table (uses imputation for missing data, so values sit slightly below the NEJM abstract)" }, "discontinued_due_to_gi_events_pct": { "semaglutide": 4.5, "placebo": 0.8 }, "citation": "Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384(11):989-1002", "url": "https://doi.org/10.1056/NEJMoa2032183" }, "other_trials": [ { "name": "STEP UP (7.2 mg)", "finding": "1,407 adults with BMI 30 or more without diabetes, 72 weeks. Mean weight change was -18.7% with 7.2 mg, -15.6% with 2.4 mg and -3.9% with placebo. 47.7%, 33.3% and 2.9% lost at least 20%. 31.2%, 15.3% and 0% lost at least 25% (UK SmPC table).", "url": "https://doi.org/10.1016/S2213-8587(25)00226-8" }, { "name": "SELECT (cardiovascular outcomes)", "finding": "17,604 adults aged 45 or over with established cardiovascular disease and BMI 27 or more, without diabetes, mean follow-up 39.8 months. Cardiovascular death, non-fatal heart attack or non-fatal stroke occurred in 6.5% with semaglutide 2.4 mg and 8.0% with placebo (hazard ratio 0.80, 95% CI 0.72 to 0.90). 16.6% versus 8.2% stopped because of adverse events.", "url": "https://doi.org/10.1056/NEJMoa2307563" }, { "name": "STEP 4 (withdrawal)", "finding": "After a 20-week run-in with 10.6% mean weight loss, 803 adults were randomised. From week 20 to 68 weight changed by -7.9% with continued semaglutide and +6.9% with placebo, a difference of 14.8 percentage points. People who stayed on semaglutide lost 17.4% in total from week 0 to 68 (SmPC).", "url": "https://doi.org/10.1001/jama.2021.3224" }, { "name": "STEP 1 extension (after stopping)", "finding": "327 participants were followed for a year after stopping. The semaglutide group had lost 17.3% by week 68, regained 11.6 percentage points by week 120 and kept a net loss of 5.6%.", "url": "https://doi.org/10.1111/dom.14725" } ], "common_side_effects": [ { "effect": "nausea", "rate_pct": 43.9, "placebo_pct": 16.1, "dose": "2.4 mg", "source_trial": "UK SmPC 4.8, 2.4 mg weight management trials over 68 weeks" }, { "effect": "diarrhoea", "rate_pct": 29.7, "placebo_pct": 15.9, "dose": "2.4 mg", "source_trial": "UK SmPC 4.8, 2.4 mg weight management trials over 68 weeks" }, { "effect": "vomiting", "rate_pct": 24.5, "placebo_pct": 6.3, "dose": "2.4 mg", "source_trial": "UK SmPC 4.8, 2.4 mg weight management trials over 68 weeks" }, { "effect": "constipation", "rate_pct": 24.2, "placebo_pct": 11.1, "dose": "2.4 mg", "source_trial": "UK SmPC 4.8, 2.4 mg weight management trials over 68 weeks" }, { "effect": "stopped treatment because of a gastrointestinal event", "rate_pct": 4.3, "placebo_pct": null, "dose": "2.4 mg", "source_trial": "UK SmPC 4.8" }, { "effect": "nausea", "rate_pct": 38.9, "placebo_pct": 12.6, "dose": "7.2 mg", "source_trial": "STEP UP (UK SmPC 4.8)" }, { "effect": "diarrhoea", "rate_pct": 24.2, "placebo_pct": 11.6, "dose": "7.2 mg", "source_trial": "STEP UP (UK SmPC 4.8)" }, { "effect": "vomiting", "rate_pct": 22.1, "placebo_pct": 5.7, "dose": "7.2 mg", "source_trial": "STEP UP (UK SmPC 4.8)" }, { "effect": "constipation", "rate_pct": 20.4, "placebo_pct": 7.6, "dose": "7.2 mg", "source_trial": "STEP UP (UK SmPC 4.8)" } ], "other_evidence": [ "UK licence includes cardiovascular risk reduction in adults with established cardiovascular disease and BMI 27 or more, based on SELECT (20% relative reduction in major cardiovascular events, 6.5% versus 8.0%).", "UK SmPC section 4.1 also lists adolescents aged 12 and over with obesity and body weight above 60 kg, and non-cirrhotic MASH with F2 to F3 fibrosis.", "7.2 mg dose: given as one 7.2 mg injection or three 2.4 mg injections one after another on the same day, at least 5 cm apart, depending on the pen supplied." ], "contraception_note": "Women of childbearing potential are advised to use contraception. The SmPC reports no clinically relevant change in exposure to oral contraceptives with semaglutide, so no extra barrier advice applies.", "pregnancy_washout": "Stop at least 2 months before a planned pregnancy.", "sources": [ { "t": "Wegovy FlexTouch SmPC (emc, last updated 22 Sep 2026)", "u": "https://www.medicines.org.uk/emc/product/13799/smpc" }, { "t": "Wegovy patient leaflet (emc)", "u": "https://www.medicines.org.uk/emc/product/13799/pil" }, { "t": "STEP 1, NEJM 2021", "u": "https://doi.org/10.1056/NEJMoa2032183" }, { "t": "STEP 4, JAMA 2021", "u": "https://doi.org/10.1001/jama.2021.3224" }, { "t": "STEP 1 extension, Diabetes Obes Metab 2022", "u": "https://doi.org/10.1111/dom.14725" }, { "t": "SELECT, NEJM 2023", "u": "https://doi.org/10.1056/NEJMoa2307563" }, { "t": "STEP UP, Lancet Diabetes Endocrinol 2025;13(11):949-963", "u": "https://doi.org/10.1016/S2213-8587(25)00226-8" }, { "t": "MHRA press release on the 7.2 mg dose, 16 Jan 2026", "u": "https://www.gov.uk/government/news/medicines-regulator-approves-up-to-72mg-dose-of-semaglutidewegovy-for-patients-with-obesity-only" } ], "notes": "STEP 1 efficacy (trial product) estimand value was not found in any source opened, so mean_loss_efficacy_pct is null. The NEJM abstract gives no 20% threshold, so pct_reaching_20 is null in the headline set. The UK SmPC gives 30.2% versus 1.7%. STEP 1 threshold percentages differ between the NEJM abstract (86.4, 69.1, 50.5) and the UK SmPC (83.5, 66.1, 47.9). STEP UP numbers come from the UK SmPC table because the Lancet full text was not readable. The SmPC table gives 31.2% reaching 25% loss with 7.2 mg while a footnote and conference reports give 33.2% (a different estimand). The widely quoted 20.7% STEP UP figure (trial product estimand) was seen only in secondary headlines and is not used. SmPC sections 6.3, 6.4 and 10 could not be read, so storage comes from the emc patient leaflet." }, "wegovy_pill": { "generic": "semaglutide (oral)", "class": "GLP-1 receptor agonist", "form": "Tablet", "frequency": "Once daily", "uk_dose_steps": [ { "dose": "1.5 mg", "min_weeks": 4, "role": "starter", "min_duration": "at least 1 month" }, { "dose": "4 mg", "min_weeks": 4, "role": "step", "min_duration": "at least 1 month" }, { "dose": "9 mg", "min_weeks": 4, "role": "step", "min_duration": "at least 1 month" }, { "dose": "25 mg", "min_weeks": null, "role": "maintenance, maximum" } ], "maintenance_doses": "25 mg once daily", "max_dose": "25 mg once daily", "missed_dose_rule": "Skip the missed dose and take the next dose the following day.", "storage": "No special temperature storage conditions. Keep in the original blister to protect from moisture and light. Shelf life 3 years.", "half_life": "Approximately 1 week", "routine": { "fasting_before": "At least 8 hours without food", "water": "Swallow whole with a sip of water, up to half a glass (120 ml)", "wait_after": "Wait at least 30 minutes before eating, drinking or taking other oral medicines" }, "key_trial": { "name": "OASIS 4", "population": "Adults with BMI 30 or more, or 27 or more with at least one obesity-related complication, without diabetes", "n": 307, "duration_weeks": 64, "dose": "25 mg", "mean_loss_treatment_regimen_pct": 13.6, "mean_loss_efficacy_pct": null, "placebo_loss_pct": 2.2, "pct_reaching_5": 76.3, "pct_reaching_10": 59.8, "pct_reaching_15": 47.0, "pct_reaching_20": 27.5, "placebo_pct_reaching": { "5": 30.5, "10": 14.1, "15": 5.4, "20": 3.0 }, "thresholds_estimand": "UK SmPC OASIS 4 table", "citation": "Wharton S, Lingvay I, Bogdanski P, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. N Engl J Med 2025;393(11):1077-1087", "url": "https://doi.org/10.1056/NEJMoa2500969" }, "other_trials": [ { "name": "OASIS 1 (50 mg, not a UK licensed dose)", "finding": "667 adults with overweight or obesity without type 2 diabetes, 68 weeks. Mean weight change was -15.1% with oral semaglutide 50 mg and -2.4% with placebo. 85% versus 26% lost at least 5%, 69% versus 12% at least 10%, 54% versus 6% at least 15% and 34% versus 3% at least 20%. Gastrointestinal adverse events occurred in 80% versus 46%.", "url": "https://doi.org/10.1016/S0140-6736(23)01185-6" } ], "common_side_effects": [ { "effect": "nausea", "rate_pct": 46.6, "placebo_pct": 18.6, "dose": "25 mg", "source_trial": "OASIS 4 (UK SmPC 4.8)" }, { "effect": "vomiting", "rate_pct": 30.9, "placebo_pct": 5.9, "dose": "25 mg", "source_trial": "OASIS 4 (UK SmPC 4.8)" }, { "effect": "constipation", "rate_pct": 20.1, "placebo_pct": 9.8, "dose": "25 mg", "source_trial": "OASIS 4 (UK SmPC 4.8)" }, { "effect": "diarrhoea", "rate_pct": 17.6, "placebo_pct": 8.8, "dose": "25 mg", "source_trial": "OASIS 4 (UK SmPC 4.8)" }, { "effect": "hair loss", "rate_pct": 6.4, "placebo_pct": 2.0, "dose": "25 mg", "source_trial": "OASIS 4 (UK SmPC 4.8)" }, { "effect": "dysaesthesia (altered skin sensation)", "rate_pct": 4.9, "placebo_pct": 0, "dose": "25 mg", "source_trial": "OASIS 4 (UK SmPC 4.8)" }, { "effect": "any gastrointestinal adverse event", "rate_pct": 74.0, "placebo_pct": 42.2, "dose": "25 mg", "source_trial": "OASIS 4 (NEJM abstract)" }, { "effect": "stopped treatment because of a gastrointestinal event", "rate_pct": 3.4, "placebo_pct": null, "dose": "25 mg", "source_trial": "OASIS 4 (UK SmPC 4.8)" } ], "other_evidence": [ "The UK SmPC cites OASIS 4 only. The 50 mg dose studied in OASIS 1 is not part of the UK licence." ], "contraception_note": "Women of childbearing potential are advised to use contraception. The SmPC reports no clinically relevant change in exposure to oral contraceptives. Semaglutide delays stomach emptying, which can affect absorption of other oral medicines.", "pregnancy_washout": "Stop at least 2 months before a planned pregnancy.", "sources": [ { "t": "Wegovy 1.5 mg tablets SmPC (emc, first authorised 11 June 2026, text revised 06/2026)", "u": "https://www.medicines.org.uk/emc/product/102344/smpc" }, { "t": "OASIS 4, NEJM 2025", "u": "https://doi.org/10.1056/NEJMoa2500969" }, { "t": "OASIS 1, Lancet 2023;402(10403):705-719", "u": "https://doi.org/10.1016/S0140-6736(23)01185-6" }, { "t": "Pharmaceutical Journal, MHRA approves semaglutide oral tablets for weight loss, 12 June 2026", "u": "https://pharmaceutical-journal.com/article/news/mhra-approves-semaglutide-oral-tablets-for-weight-loss" } ], "notes": "Licensed UK steps confirmed from the SmPC: 1.5 mg, 4 mg, 9 mg, 25 mg, at least 1 month on each. min_weeks 4 stands in for the SmPC wording of 1 month. OASIS 4 ran for 71 weeks in total with the weight endpoint at week 64. The 13.6% figure is the primary analysis in the NEJM abstract and the SmPC. An efficacy estimand value was not verified, so it is null. UK availability was not verified: an emc search listing for the 25 mg tablet carried the label 'Reference only - not currently marketed in the UK', and the Pharmaceutical Journal report of 12 June 2026 said pharmacies were waiting for a launch date." }, "foundayo": { "generic": "orforglipron", "class": "Oral non-peptide (small molecule) GLP-1 receptor agonist", "form": "Film-coated tablet", "frequency": "Once daily, at any time of day, with or without food, no water restriction", "uk_dose_steps": [ { "dose": "0.8 mg", "min_days": 30, "min_weeks": null, "role": "starter" }, { "dose": "2.5 mg", "min_days": 30, "min_weeks": null, "role": "step" }, { "dose": "5.5 mg", "min_days": 30, "min_weeks": null, "role": "step" }, { "dose": "9 mg", "min_days": 30, "min_weeks": null, "role": "step" }, { "dose": "14.5 mg", "min_days": 30, "min_weeks": null, "role": "step" }, { "dose": "17.2 mg", "min_days": null, "min_weeks": null, "role": "maximum" } ], "maintenance_doses": "The UK SmPC names no single maintenance dose. After 5.5 mg the dose can rise to 9 mg, 14.5 mg or 17.2 mg, each after at least 30 days, based on response and tolerability.", "max_dose": "17.2 mg once daily (9 mg once daily with a strong CYP3A4 inhibitor)", "missed_dose_rule": "Take the missed dose as soon as possible. Do not take more than one tablet in a day and do not double up. The UK SmPC gives no hours cut-off. The US label adds that after 7 or more missed doses in a row, dose escalation restarts at a lower dose.", "storage": "UK patient leaflet: keep in the original package to protect from light. No UK storage temperature was verified. The US label states 20 to 25 degrees C with excursions to 15 to 30 degrees C.", "half_life": "Approximately 29 to 49 hours (US FDA label, UK SmPC section 5.2 not readable)", "tablet_to_trial_capsule_equivalence": "Tablets and the hard capsules used in trials are not interchangeable mg for mg. Per the UK SmPC the 0.8 mg tablet matches the 1 mg capsule and the 17.2 mg tablet matches the 36 mg capsule. The US label reports trial results under 5.5 mg, 9 mg and 17.2 mg, matching capsule doses 6 mg, 12 mg and 36 mg.", "key_trial": { "name": "ATTAIN-1", "population": "Adults with BMI 30 or more, or 27 to under 30 with at least one weight-related complication, without diabetes. Mean age 45, 64.2% women, mean baseline weight 103.2 kg.", "n": 3127, "duration_weeks": 72, "dose": "36 mg capsule (equivalent to the 17.2 mg tablet)", "mean_loss_treatment_regimen_pct": 11.2, "mean_loss_efficacy_pct": 12.4, "placebo_loss_pct": 2.1, "placebo_loss_efficacy_pct": 0.9, "pct_reaching_5": 71.8, "pct_reaching_10": 54.6, "pct_reaching_15": 36.0, "pct_reaching_20": 18.4, "placebo_pct_reaching": { "5": 26.8, "10": 12.9, "15": 5.9, "20": 2.8 }, "thresholds_estimand": "treatment-regimen (NEJM)", "by_dose": { "6 mg capsule (5.5 mg tablet)": { "n": 723, "treatment_regimen_pct": 7.5, "efficacy_pct": 7.8, "loss_kg_efficacy": 8.0, "pct_reaching_treatment_regimen": { "5": 60.6, "10": 33.3, "15": 15.1, "20": 6.4 }, "pct_reaching_efficacy": { "5": 63.8, "10": 35.9, "15": 16.5, "20": 7.2 } }, "12 mg capsule (9 mg tablet)": { "n": 725, "treatment_regimen_pct": 8.4, "efficacy_pct": 9.3, "loss_kg_efficacy": 9.4, "pct_reaching_treatment_regimen": { "5": 63.5, "10": 40.0, "15": 20.3, "20": 9.0 }, "pct_reaching_efficacy": { "5": 69.3, "10": 45.1, "15": 24.0, "20": 11.4 } }, "36 mg capsule (17.2 mg tablet)": { "n": 730, "treatment_regimen_pct": 11.2, "efficacy_pct": 12.4, "loss_kg_efficacy": 12.4, "pct_reaching_treatment_regimen": { "5": 71.8, "10": 54.6, "15": 36.0, "20": 18.4 }, "pct_reaching_efficacy": { "5": 77.1, "10": 59.6, "15": 39.6, "20": 20.1 } }, "placebo": { "n": 949, "treatment_regimen_pct": 2.1, "efficacy_pct": 0.9, "loss_kg_efficacy": 1.0, "pct_reaching_treatment_regimen": { "5": 26.8, "10": 12.9, "15": 5.9, "20": 2.8 }, "pct_reaching_efficacy": { "5": 22.1, "10": 8.6, "15": 3.6, "20": 1.6 } } }, "waist_change_cm_efficacy": { "6 mg": -7.5, "12 mg": -9.0, "36 mg": -11.1, "placebo": -2.1 }, "discontinued_due_to_adverse_events_pct": { "6 mg": 5.3, "12 mg": 7.9, "36 mg": 10.3, "placebo": 2.7 }, "citation": "Wharton S, Aronne LJ, Stefanski A, et al. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. N Engl J Med, published online 16 September 2025", "url": "https://doi.org/10.1056/NEJMoa2511774" }, "other_trials": [ { "name": "ATTAIN-2 (obesity with type 2 diabetes)", "finding": "72 weeks. Mean weight change (efficacy estimand, UK SmPC) was -5.5% with 6 mg, -7.8% with 12 mg and -10.5% with 36 mg versus -2.2% with placebo. 72.8% versus 24.4% lost at least 5% on the top dose, 50.1% versus 7.0% at least 10%. HbA1c fell by 1.3, 1.6 and 1.8 percentage points versus 0.1.", "url": "https://doi.org/10.1016/S0140-6736(25)02165-8" }, { "name": "ATTAIN-MAINTAIN (maintenance after injections)", "finding": "376 adults who finished 72 weeks of tirzepatide or semaglutide in SURMOUNT-5 were randomised to orforglipron or placebo for 52 weeks. After tirzepatide, orforglipron kept 74.7% of the earlier weight loss versus 49.2% with placebo. After semaglutide, 79.3% versus 37.6%. Average regain on orforglipron was about 5 kg after tirzepatide and about 1 kg after semaglutide.", "url": "https://doi.org/10.1038/s41591-026-04386-7" } ], "common_side_effects": [ { "effect": "nausea", "rate_pct": 33.7, "placebo_pct": 10.4, "dose": "36 mg capsule (17.2 mg tablet)", "source_trial": "ATTAIN-1 (Lilly press release, 16 Sep 2025)" }, { "effect": "constipation", "rate_pct": 25.4, "placebo_pct": 9.3, "dose": "36 mg capsule (17.2 mg tablet)", "source_trial": "ATTAIN-1 (Lilly press release, 16 Sep 2025)" }, { "effect": "vomiting", "rate_pct": 24.0, "placebo_pct": 3.5, "dose": "36 mg capsule (17.2 mg tablet)", "source_trial": "ATTAIN-1 (Lilly press release, 16 Sep 2025)" }, { "effect": "diarrhoea", "rate_pct": 23.1, "placebo_pct": 9.6, "dose": "36 mg capsule (17.2 mg tablet)", "source_trial": "ATTAIN-1 (Lilly press release, 16 Sep 2025)" }, { "effect": "abdominal pain", "rate_pct": 14, "placebo_pct": 7, "dose": "17.2 mg tablet", "source_trial": "Pooled weight management trials (FDA Foundayo label Table 1, whole numbers)" }, { "effect": "dyspepsia (indigestion)", "rate_pct": 13, "placebo_pct": 4, "dose": "17.2 mg tablet", "source_trial": "Pooled weight management trials (FDA Foundayo label Table 1, whole numbers)" }, { "effect": "any gastrointestinal disorder", "rate_pct": 68.7, "placebo_pct": 36.3, "dose": "36 mg capsule (17.2 mg tablet)", "source_trial": "Weight management studies (UK SmPC 4.8)" }, { "effect": "stopped treatment because of an adverse event", "rate_pct": 10.3, "placebo_pct": 2.7, "dose": "36 mg capsule (17.2 mg tablet)", "source_trial": "ATTAIN-1 (NEJM Table 4)" } ], "side_effects_lower_doses_attain1": { "6 mg": { "nausea": 28.9, "constipation": 21.7, "diarrhoea": 21.0, "vomiting": 13.0 }, "12 mg": { "nausea": 35.9, "constipation": 29.8, "diarrhoea": 22.8, "vomiting": 21.4 }, "source": "https://investor.lilly.com/node/52896" }, "other_evidence": [ "UK licence also covers adults with insufficiently controlled type 2 diabetes.", "ATTAIN-MAINTAIN change from the SURMOUNT-5 baseline: -16.5% with orforglipron versus -12.6% with placebo after tirzepatide, and -14.9% versus -7.9% after semaglutide (Nature Medicine 2026). The source page printed the tirzepatide placebo value as +12.6%, which looks like a sign error. Confirm in the paper before quoting." ], "contraception_note": "Use effective contraception during treatment. Orforglipron can make oral hormonal contraceptives less effective. Switch to a non-oral method or add a barrier method for 30 days after starting and for 30 days after each dose increase.", "pregnancy_washout": "Stop at least 3 weeks before a planned pregnancy.", "sources": [ { "t": "Foundayo 0.8 mg film-coated tablets SmPC (emc, updated 14 Aug 2026)", "u": "https://www.medicines.org.uk/emc/product/102527/smpc" }, { "t": "Foundayo patient leaflet (emc)", "u": "https://www.medicines.org.uk/emc/product/102527/pil" }, { "t": "MHRA press release, 10 Aug 2026", "u": "https://www.gov.uk/government/news/uk-first-in-europe-to-authorise-orforglipron-for-weight-management-and-type-2-diabetes" }, { "t": "ATTAIN-1, NEJM 2025", "u": "https://doi.org/10.1056/NEJMoa2511774" }, { "t": "Lilly ATTAIN-1 press release, 16 Sep 2025", "u": "https://investor.lilly.com/node/52896" }, { "t": "ATTAIN-2, Lancet 2025", "u": "https://doi.org/10.1016/S0140-6736(25)02165-8" }, { "t": "ATTAIN-MAINTAIN, Nature Medicine 2026;32(7):2679-2687", "u": "https://doi.org/10.1038/s41591-026-04386-7" }, { "t": "Foundayo US prescribing information (FDA label, revised 07/2026)", "u": "https://pi.lilly.com/us/foundayo-uspi.pdf" } ], "notes": "Six UK tablet strengths confirmed: 0.8, 2.5, 5.5, 9, 14.5 and 17.2 mg, at least 30 days per step (min_days is used, min_weeks is null). Trials dosed hard capsules of 6, 12 and 36 mg. Half-life and storage temperature come from the US label because SmPC sections 5.2 and 6.4 were not readable on emc. ATTAIN-2 participant count, volume and pages were not verified (the Lancet page was blocked). ATTAIN-2 figures are from the UK SmPC table. Placebo discontinuation in ATTAIN-1 is 2.7% in the NEJM table and 2.6% in the NEJM text." } }, "head_to_head": [ { "trial": "SURMOUNT-5", "finding": "Tirzepatide (10 or 15 mg) versus semaglutide (1.7 or 2.4 mg), 751 adults with obesity without type 2 diabetes, 72 weeks, open label. Mean weight change -20.2% versus -13.7%. Waist change -18.4 cm versus -13.0 cm. Aronne LJ et al, N Engl J Med 2025;393(1):26-36.", "url": "https://doi.org/10.1056/NEJMoa2416394" }, { "trial": "STEP UP", "finding": "Semaglutide 7.2 mg versus 2.4 mg versus placebo, 1,407 adults with BMI 30 or more, 72 weeks. Mean weight change -18.7% versus -15.6% versus -3.9% (UK SmPC).", "url": "https://doi.org/10.1016/S2213-8587(25)00226-8" } ], "regain_after_stopping": [ { "trial": "SURMOUNT-4", "finding": "After 36 weeks on tirzepatide (20.9% mean loss), people switched to placebo regained 14.0% of body weight over 52 weeks while people who continued lost a further 5.5%. 16.6% of the placebo group kept at least 80% of the earlier loss versus 89.5% on tirzepatide.", "url": "https://doi.org/10.1001/jama.2023.24945" }, { "trial": "STEP 4", "finding": "After 20 weeks on semaglutide (10.6% mean loss), people switched to placebo regained 6.9% over 48 weeks while people who continued lost a further 7.9%.", "url": "https://doi.org/10.1001/jama.2021.3224" }, { "trial": "STEP 1 extension", "finding": "One year after stopping semaglutide 2.4 mg, participants had regained 11.6 percentage points of a 17.3% loss, about two-thirds, leaving a net loss of 5.6% at week 120.", "url": "https://doi.org/10.1111/dom.14725" }, { "trial": "ATTAIN-MAINTAIN", "finding": "After stopping weekly injections, placebo groups kept 49.2% (after tirzepatide) and 37.6% (after semaglutide) of the earlier loss at 52 weeks. People switched to orforglipron kept 74.7% and 79.3%.", "url": "https://doi.org/10.1038/s41591-026-04386-7" } ], "uk_regulatory": { "mounjaro_licence": "MHRA authorised Mounjaro for weight management on 8 November 2023, for adults with BMI 30 or more, or 27 to under 30 with at least one weight-related comorbidity. Maximum 15 mg once weekly. No separate UK indication for obstructive sleep apnoea appears in SmPC section 4.1.", "wegovy_7_2mg_uk": "MHRA approved a maximum dose of up to 7.2 mg once weekly on 6 January 2026 (announced 16 January 2026), for adults with BMI 30 or more only, after at least 4 weeks on 2.4 mg. Not for BMI under 30 and not for cardiovascular risk reduction.", "wegovy_pill_uk": "Licensed. Wegovy tablets have a UK marketing authorisation for weight management in adults with BMI 30 or more, or 27 to under 30 with at least one weight-related comorbidity. Date of first authorisation 11 June 2026 (SmPC section 9). Steps 1.5 mg, 4 mg, 9 mg, 25 mg.", "wegovy_pill_uk_licensed": true, "wegovy_pill_uk_licence_date": "2026-06-11", "foundayo_uk": "Licensed. MHRA authorised Foundayo (orforglipron) on 10 August 2026 for weight management in adults with BMI 30 or more, or 27 to under 30 with at least one weight-related comorbidity, and for insufficiently controlled type 2 diabetes. The UK was the first country in Europe to authorise it.", "foundayo_uk_licensed": true, "foundayo_uk_licence_date": "2026-08-10", "sources": [ { "t": "MHRA Mounjaro weight management press release", "u": "https://www.gov.uk/government/news/mhra-authorises-diabetes-drug-mounjaro-tirzepatide-for-weight-management-and-weight-loss" }, { "t": "MHRA Wegovy 7.2 mg press release", "u": "https://www.gov.uk/government/news/medicines-regulator-approves-up-to-72mg-dose-of-semaglutidewegovy-for-patients-with-obesity-only" }, { "t": "Wegovy tablets SmPC section 9", "u": "https://www.medicines.org.uk/emc/product/102344/smpc" }, { "t": "Pharmaceutical Journal on the MHRA oral semaglutide approval", "u": "https://pharmaceutical-journal.com/article/news/mhra-approves-semaglutide-oral-tablets-for-weight-loss" }, { "t": "MHRA Foundayo press release", "u": "https://www.gov.uk/government/news/uk-first-in-europe-to-authorise-orforglipron-for-weight-management-and-type-2-diabetes" }, { "t": "EMA Q&A on Mounjaro and OSA", "u": "https://www.ema.europa.eu/en/documents/medicine-qa/questions-answers-outcome-assessment-use-mounjaro-treatment-obstructive-sleep-apnoea_en.pdf" } ], "notes": "The Wegovy pill date comes from SmPC section 9. The Pharmaceutical Journal reports the MHRA statement as published on 11 June 2026. The gov.uk press release for the pill was not opened. UK launch and stock status for the Wegovy pill and Foundayo were not verified. The EMA OSA decision is an EU decision. The UK position rests on the UK SmPC wording alone." }, "clinical_review_status": "pending" }