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Tirzepatide
Dual GIP / GLP-1 agonist
Tirzepatide works on both the GIP and GLP-1 receptors. In head-to-head trials that dual action produced more weight loss than GLP-1 alone, which is why it is usually the second thing people ask about.
The trade-off is patience. The ladder is longer and the side-effect window at each step is wider, so a physician will hold you at a dose until it is genuinely comfortable rather than moving on schedule.
Your clinician sets the actual schedule. This is the standard ladder and the one they start from.
Multiple large randomised controlled trials in people, published in peer-reviewed journals, with regulatory approval behind them.
Mean body-weight change at 72 weeks on 15mg weekly, against −3.1% on placebo
SURMOUNT-1 · NEJM 2022Against semaglutide's −13.7% in the first head-to-head trial of the two
SURMOUNT-5 · NEJM 2025Discontinued for GI side effects, against 5.6% on semaglutide
SURMOUNT-5 · NEJM 2025What it is
Tirzepatide is a dual agonist: it activates the GIP receptor as well as the GLP-1 receptor. GIP is a second incretin hormone, and engaging both appears to do more than engaging either alone. FDA-approved for type 2 diabetes in 2022 and for weight management in 2023.
How it works
The same GLP-1 machinery as semaglutide — slowed gastric emptying, glucose-dependent insulin release, reduced appetite signalling — plus GIP activity that appears to change how fat tissue handles energy.
What the evidence actually says
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2022
SURMOUNT-1
2,539 adults. Mean −20.9% body weight at 72 weeks on 15mg, against −3.1% on placebo — the largest effect size published for a weight-management drug at the time.
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2023
FDA approval
Approved in November for chronic weight management in adults with obesity, or overweight with a weight-related condition.
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2025
SURMOUNT-5
751 adults, 72 weeks, the first direct comparison against semaglutide. Tirzepatide −20.2% versus semaglutide −13.7%, and −18.4cm versus −13.0cm waist circumference. Fewer discontinued for GI events on tirzepatide.
What the first months look like
- Weeks 1–42.5mg weekly. As with semaglutide, an adaptation dose rather than a therapeutic one.
- Weeks 5–20Steps of 2.5mg, no more often than every four weeks. A longer ladder than semaglutide's, and a prescriber will hold you on a rung until it is comfortable.
- Month 6+Maintenance, usually 10–15mg. Weight was still decreasing at 72 weeks in trial.
Who this is not for
- A personal or family history of medullary thyroid carcinoma, or MEN2.
- Pregnancy, or planning pregnancy within two months.
- A previous episode of pancreatitis, without a prescriber reviewing it first.
Sources
- Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205–216.
- SURMOUNT-5: Greater Loss of Weight and Waist Circumference With Tirzepatide Than Semaglutide — American College of Cardiology, 2025.
- Tirzepatide for Obesity Treatment and Diabetes Prevention. N Engl J Med.
Figures are quoted from the published trials and were last checked in August 2026. We update this page when the evidence changes.