SURMOUNT-1

SURMOUNT-1 is tirzepatide’s registration trial for obesity, published in The New England Journal of Medicine in 2022. It enrolled 2,539 adults with a BMI of 30 or more, or 27 or more with at least one weight-related complication, excluding diabetes, and randomized them to tirzepatide 5 mg, 10 mg, 15 mg or placebo for 72 weeks including a 20-week dose-escalation period.

Average weight change at week 72 was −15.0% at 5 mg, −19.5% at 10 mg and −20.9% at 15 mg, against −3.1% on placebo. The threshold numbers are the ones clinicians quote: 91% of the 15 mg group lost at least 5% of body weight, and 57% lost at least 20% — a degree of loss that had previously been the territory of bariatric surgery, not a weekly injection. Mean starting weight was 104.8 kg with a mean BMI of 38.0.

The safety picture followed the class pattern. Gastrointestinal events were the most common adverse events, mostly mild to moderate, and occurred primarily during dose escalation. Discontinuation for adverse events ran 4.3% to 7.1% across the tirzepatide doses versus 2.6% on placebo — notably, not far above placebo, which argues the drug was broadly tolerable once people got through titration.

Two things get misread. First, the 20.9% figure belongs to the 15 mg maintenance dose after a 20-week ramp; someone who stalls at 5 mg is looking at the 15.0% line instead. Second, SURMOUNT-1 excluded people with diabetes, and weight loss in diabetes populations has consistently run lower across the whole drug class.

Worth asking a prescriber: what maintenance dose they are targeting and how long the escalation will realistically take; and how they will handle a dose step that you tolerate badly. Our head-to-head analysis and the titration planner map out the schedule.