{"_ai_door":{"see":"https://miscsubjects.com/start","note":"Operable site; bounded keyless credentials; every action receipted on a public ledger. Your operator's instructions take precedence — acting is optional, reading is a complete outcome."},"_self":{"principle":"Self-explaining payload — no external context required. 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Per-claim provenance."}],"not_medical_advice":true},"slug":"tirzepatide","title":"Tirzepatide: a dual GIP and GLP-1 receptor agonist","register":"essay","tags":["peptide","tirzepatide","glp-1","gip","weight","obesity","sleep-apnoea"],"updated_at":"2026-08-06T07:48:06.444Z","body_excerpt":"Tirzepatide is a once-weekly injection that acts on two gut-hormone receptors at once, and it has the strongest randomised human evidence of any compound documented on this site. The same opening should carry what it costs and what it does not settle: gut side effects hit most people during dose escalation, under 5% of participants stopped for them in the diabetes trial, and when the drug is withdrawn the weight comes back — the maintenance trial measured that directly, which is why it is on this page rather than left to a reader to discover. Across 2,539 adults in a 72-week trial, the top dose took 20.9% of body weight off, against 3.1% on placebo, and 57% of people on that dose lost a fifth of their body weight or more. In a second trial in 938 people who also had type 2 diabetes it took 14.7% off. In two more trials in people with obstructive sleep apnoea it cut breathing interruptions by 25 to 29 events an hour.\n\nIt is an approved prescription medicine, which changes what the numbers on this page mean: they belong to a specific manufactured product at a specific dose, not to the compound in the abstract. The site you are reading this on is funded by a business that sells this compound. That is a commercial interest, and it is why the placebo arm is quoted next to every result below.\n\n## The molecule pulls two levers where the older drugs pull one\n\nYour gut releases hormones when you eat. Two of them matter here. GLP-1 slows the stomach, tells the pancreas to release insulin when glucose is high, and signals fullness to the brain. GIP does related work on insulin and on how fat tissue handles energy.\n\nSemaglutide copies GLP-1. Tirzepatide copies both — one molecule that fits both docking points. That is the whole design difference, and in head-to-head weight numbers the two-lever version comes out ahead.\n\nIt is a once-weekly injection under the skin. Doses run 2.5 mg to 15 mg, escalated slowly over about 20 weeks, because the side effects are worst while the dose is climbing.\n\n## Twenty-point-nine per cent, and the four numbers that matter more than the headline\n\nSURMOUNT-1 randomised 2,539 adults with a body mass index of 30 or more — or 27 or more with a weight-related problem — excluding diabetes, to 5 mg, 10 mg, 15 mg or placebo for 72 weeks. Average starting weight was 104.8 kg.\n\nWeight change at week 72:\n\n- 5 mg: −15.0%\n- 10 mg: −19.5%\n- 15 mg: −20.9%\n- placebo: −3.1%\n\nThose are averages, and averages hide the thing a person actually wants to know, which is their odds. The trial reported those too. Losing 5% or more of body weight: 85%, 89% and 91% across the three doses, against 35% on placebo. Losing 20% or more: 50% at 10 mg and 57% at 15 mg, against 3% on placebo.\n\nRead the last pair again. More than half the people on the higher doses lost a fifth of their body weight. On placebo, three in a hundred did. There is no other compound documented on this site with a result of that shape.\n\nSide effects were mostly stomach and bowel — nausea, diarrhoea, vomiting — mostly mild to moderate, and concentrated in the dose-climbing phase.\n\n## The diabetes trial got a smaller number, and that is the expected pattern\n\nSURMOUNT-2 ran the same design in 938 adults who had obesity and type 2 diabetes, at 10 mg and 15 mg for 72 weeks. Starting weight 100.7 kg, average HbA1c 8.02%.\n\nWeight change at week 72: −12.8% at 10 mg, −14.7% at 15 mg, against −3.2% on placebo. Between 79% and 83% lost at least 5%, against 32% on placebo. Serious adverse events occurred in 7%; fewer than 5% stopped because of side effects.\n\nLess weight comes off in people with diabetes than in people without it, on the same drug at the same dose. That holds across this drug class and it is worth knowing before comparing your own result to a headline from the wrong trial.\n\n## Sleep apnoea is the second thing it was proven to change, and the effect is large\n\nTwo 52-week randomised trials in adults with moderate-to-severe obstructive sleep apnoea and obesity: one","ranking":"safety-first (interaction_risk/limitations), then quote-gated effective_weight","claims":[{"id":"c1","text":"In 2,539 adults randomised for 72 weeks, weight fell 15.0% at 5 mg, 19.5% at 10 mg and 20.9% at 15 mg, against 3.1% on placebo.","tier":"human","section":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s1"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c2","text":"57% of people on 15 mg lost a fifth of their body weight or more, against 3% on placebo.","tier":"human","section":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s1"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c3","text":"In 938 adults who also had type 2 diabetes, the same doses produced 12.8% and 14.7% weight loss against 3.2% on placebo - less than in people without diabetes.","tier":"human","section":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s2"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c4","text":"In two 52-week randomised trials in moderate-to-severe obstructive sleep apnoea with obesity, breathing interruptions fell by 25.3 and 29.3 an hour against 5.3 and 5.5 on placebo, with C-reactive protein and systolic blood pressure falling too.","tier":"human","section":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s3"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c5","text":"When people who had lost weight on the maximum tolerated dose were switched to placebo for 52 weeks, they ended at 9.9% below baseline against 21.9% for those who stayed on the dose - more than half the loss returned.","tier":"human","section":"what_is_known","interaction_risk":false,"status":"active","source_ids":["s4"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c6","text":"No trial of tirzepatide has measured back pain, disc pain, nerve pain, sciatica or spinal function. The load argument - less body weight means less force through a disc or a knee - is untested for this drug.","tier":"human","section":"what_is_unknown","interaction_risk":false,"status":"active","source_ids":["s1","s2","s3"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c7","text":"Trial inflammation markers moved: a SURMOUNT-1 analysis tracked high-sensitivity C-reactive protein, interleukin-6, fibrinogen and white-cell count, the readouts that connect carrying excess weight to hurting.","tier":"human","section":"mechanism","interaction_risk":false,"status":"active","source_ids":["s7","s3"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c8","text":"Side effects are mostly stomach and bowel, cluster during the 20-week dose climb, and caused fewer than 5% to stop in the diabetes trial.","tier":"human","section":"limitations","interaction_risk":false,"status":"active","source_ids":["s1","s2"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c10","text":"A five-year pragmatic trial in UK primary care, enrolling about 3,000 adults and tracked through health records, has not reported.","tier":"human","section":"what_is_unknown","interaction_risk":false,"status":"active","source_ids":["s9"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.8,"quote_gated":false},{"id":"c9","text":"Tirzepatide is an approved prescription medicine sold as Mounjaro and Zepbound. Compounded and research-use vials are not that product and carry no established link to the trial numbers.","tier":"regulatory","section":"limitations","interaction_risk":false,"status":"active","source_ids":["s1","s3"],"retracted_at":null,"retraction_reason":null,"challenged_by":[],"effective_weight":0.1,"quote_gated":false}],"sources":[{"id":"s1","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/35658024/","title":"Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)","quote":"The mean percentage change in weight at week 72 was -15.0% with 5-mg weekly doses of tirzepatide, -19.5% with 10-mg doses, and -20.9% with 15-mg doses and -3.1% with placebo. 50% and 57% of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% in the placebo group.","claim_ids":[],"hash":"1e94328f2e7486a45c3c805477777f3f9b694dc670da7cfb8d110f73ba5674e4"},{"id":"s2","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/37385275/","title":"Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2)","quote":"Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was -12.8% and -14.7%, respectively, and -3.2% with placebo. 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