# Tirzepatide Weight Loss: The SURMOUNT Trial Evidence > Tirzepatide weight loss results: SURMOUNT-1 −20.9% at 72 weeks, SURMOUNT-5 superiority over semaglutide, SURMOUNT-4 maintenance data, and what discontinuation means for long-term outcomes. Fully cited. A dedicated reading of the tirzepatide weight-loss evidence base — every key result cited to its source. ## The short version Tirzepatide weight loss results are the largest ever recorded in a major FDA-reviewed obesity trial. In SURMOUNT-1, adults with obesity or overweight lost an average of 20.9% of their body weight over 72 weeks on the highest dose — compared to 3.1% on placebo. That is roughly five to six times more weight loss than the inactive comparator. In a direct head-to-head comparison with the leading alternative (SURMOUNT-5), tirzepatide produced 20.2% weight loss compared to 13.7%, a statistically significant difference. These are mean results — individual results vary, and a subset of participants lose less than 5%. When people stopped taking tirzepatide in trial extensions, most of the weight came back, confirming it works as a long-term therapy rather than a short course. ## SURMOUNT-1: the pivotal tirzepatide weight loss trial SURMOUNT-1, published in the New England Journal of Medicine in 2022, is the foundational obesity efficacy trial for tirzepatide. The phase 3 double-blind randomised controlled trial enrolled 2,539 adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related complication and without type 2 diabetes. Participants were randomised to once-weekly subcutaneous tirzepatide at 5 mg, 10 mg, or 15 mg, or placebo, for 72 weeks following a 20-week dose-escalation schedule [4]. Mean body-weight change at week 72: - **Tirzepatide 5 mg:** −15.0% (vs −3.1% with placebo) - **Tirzepatide 10 mg:** −19.5% (vs −3.1% with placebo) - **Tirzepatide 15 mg:** −20.9% (vs −3.1% with placebo) Proportion of participants achieving ≥20% weight loss at 72 weeks: 50.3% on tirzepatide 15 mg versus 3.1% on placebo [4]. Gastrointestinal adverse events were the most common side effects and were mostly mild to moderate, occurring primarily during dose escalation. The SURMOUNT-CN extension confirmed comparable tirzepatide weight loss results in Chinese adults with obesity: −17.5% on tirzepatide 15 mg versus −2.3% on placebo at week 52 [29], supporting cross-ethnic generalisability. ## SURMOUNT-5: tirzepatide weight loss head-to-head SURMOUNT-5, published in the New England Journal of Medicine in 2025, is the first powered head-to-head comparison of tirzepatide weight loss results against the leading comparator in adults with obesity without type 2 diabetes. The open-label phase 3b trial enrolled 751 adults and randomised them to the maximum tolerated dose of tirzepatide (10 or 15 mg) or the maximum tolerated dose of semaglutide (1.7 or 2.4 mg) once weekly for 72 weeks [5]. Least-squares mean weight change at week 72: - **Tirzepatide (MTD):** −20.2% - **Semaglutide (MTD):** −13.7% - **Treatment difference:** −6.5 percentage points (p<0.001) Tirzepatide also produced greater reductions in waist circumference and higher proportions reaching every weight-loss threshold (≥10%, ≥15%, ≥20%, ≥25%). This is the highest-quality direct comparison in the obesity weight-management literature to date and represents the benchmark by which tirzepatide weight loss is now measured. ## SURMOUNT-4: tirzepatide weight loss maintenance and discontinuation SURMOUNT-4, published in JAMA in 2024, addressed the key question that follows initial weight loss: what happens when people stop? The trial enrolled 670 participants after a 36-week open-label lead-in period during which all participants lost a mean of 20.9% of body weight. They were then randomised to continued tirzepatide or placebo for an additional 52 weeks [9]. Mean percent weight change from week 36 to week 88: - **Continued tirzepatide:** −5.5% (further loss) - **Switched to placebo:** +14.0% (weight regained) - **Treatment difference:** −19.4 percentage points (p<0.001) By week 88, 89.5% of participants continuing tirzepatide had maintained ≥80% of their lead-in weight loss, versus 16.6% on placebo. The overall mean reduction from baseline (week 0) to week 88 was −25.3% with continued tirzepatide versus −9.9% with placebo. SURMOUNT-4 establishes tirzepatide as a chronic therapy — the weight loss it produces does not persist after discontinuation in most patients. SURMOUNT-MAINTAIN (Lancet, 2026) extended this finding to a lower 5 mg maintenance dose: −16.6% from baseline to week 112 versus −9.9% on placebo, demonstrating that a reduced maintenance dose can preserve substantial weight reduction over an additional year [12]. A 2025 systematic review and meta-analysis quantified weight regain after stopping across incretin therapies: the pooled semaglutide/tirzepatide group regained a mean of 9.69 kg (95% CI 5.78–13.60) after discontinuation [21]. The [Tirzepatide effects](/effects) page covers what this means for long-term planning. ## Tirzepatide weight loss — the body composition picture Not all weight lost is fat. A SURMOUNT-1 DXA (dual-energy X-ray absorptiometry — a body-composition scan) substudy found that approximately 75% of the weight lost was fat mass and approximately 25% was lean (primarily muscle) mass [18]. A systematic review across incretin trials put the median muscle-attributable share of weight loss near 28% [19]. A narrative review described this lean-mass reduction as comparable to a decade or more of age-related muscle loss and recommended resistance exercise to help preserve muscle during tirzepatide treatment [20]. This is a clinically relevant finding for the [tirzepatide weight loss](/weight-loss) picture: the scale results are striking, but they include a meaningful lean-mass component that warrants attention, particularly for older adults or those with existing low muscle mass. See [Tirzepatide effects](/effects) for the full body-composition and safety discussion. --- Forward-looking summaries of the published tirzepatide trial record — evidence on the page, not advice in the room.