Tirzepatide Weight Loss Timeline UK 2026 Research Reference: SURMOUNT Trial Data by Week, Dose-Response and Long-Term Maintenance

Last updated: April 2026 · UK research-grade reference · For laboratory research use only — not for human consumption

Table of Contents

• 1. Overview — the SURMOUNT programme
• 2. SURMOUNT-1 primary results
• 3. Week-by-week weight-loss trajectory (15 mg)
• 4. Dose-response: 5 mg vs 10 mg vs 15 mg
• 5. Response-rate distributions
• 6. SURMOUNT-2 — T2DM cohort
• 7. SURMOUNT-3 — intensive behavioural therapy
• 8. SURMOUNT-4 — withdrawal trial
• 9. SURMOUNT-5 — head-to-head vs semaglutide
• 10. SURMOUNT-OSA — obstructive sleep apnoea
• 11. Body composition — lean vs fat mass
• 12. Is there a plateau at 72 weeks?
• 13. UK research protocol design implications
• FAQ
• References

1. Overview — the SURMOUNT programme

The SURMOUNT programme is Eli Lilly’s Phase 3 clinical programme for tirzepatide in obesity and obesity-related indications. Running from 2019 through 2025 and ongoing, it comprises SURMOUNT-1 through SURMOUNT-5 (weight-loss), SURMOUNT-OSA (obstructive sleep apnoea), SYNERGY-NASH (MASH), and SURPASS-CVOT (cardiovascular outcomes in T2DM, running).

SURMOUNT-1 (NCT04184622) is the reference trial — 2,539 adults without diabetes (BMI ≥30, or ≥27 with weight-related comorbidity) randomised to tirzepatide 5, 10, or 15 mg weekly or placebo, for 72 weeks. Published Jastreboff AM et al, N Engl J Med 2022;387:205–216.

2. SURMOUNT-1 primary results

72-week primary and key secondary endpoints:

• Mean body-weight change: 5 mg −15.0%, 10 mg −19.5%, 15 mg −20.9%, placebo −3.1%
• Mean absolute weight change: 5 mg −16.0 kg, 10 mg −21.4 kg, 15 mg −22.5 kg, placebo −2.4 kg
• ≥5% weight loss: 5 mg 85%, 10 mg 89%, 15 mg 91%, placebo 35%
• ≥10% weight loss: 5 mg 69%, 10 mg 78%, 15 mg 83%, placebo 15%
• ≥15% weight loss: 5 mg 50%, 10 mg 65%, 15 mg 70%, placebo 7%
• ≥20% weight loss: 5 mg 30%, 10 mg 50%, 15 mg 57%, placebo 3%
• ≥25% weight loss: 5 mg 15%, 10 mg 32%, 15 mg 36%, placebo ~1%

SURMOUNT-1 established tirzepatide as the most effective obesity pharmacotherapy at the time of its 2022 publication, a position subsequently challenged by retatrutide and maintained over semaglutide.

3. Week-by-week weight-loss trajectory (15 mg)

SURMOUNT-1 15 mg arm approximate time-course:

• Week 4: ~−2.5%
• Week 8: ~−4%
• Week 12: ~−6%
• Week 16: ~−8%
• Week 20: ~−10%
• Week 24: ~−11.5%
• Week 28: ~−13%
• Week 36: ~−15%
• Week 44: ~−16.5%
• Week 52: ~−18%
• Week 60: ~−19.5%
• Week 72: −20.9% (primary endpoint)

The curve continues to slope downward at week 72, suggesting additional loss would occur with longer observation. This differs from semaglutide’s STEP-5 data which showed near-plateau by week 68-104.

4. Dose-response: 5 mg vs 10 mg vs 15 mg

The three approved obesity doses show a clear dose-response:

• 5 mg → 15 mg: adds ~6 percentage points (−15.0% → −20.9%)
• 5 mg → 10 mg: adds ~4.5 percentage points (−15.0% → −19.5%)
• 10 mg → 15 mg: adds ~1.5 percentage points (−19.5% → −20.9%)

The dose-response is approaching saturation between 10 mg and 15 mg. For research protocol design, 10 mg is often the “efficient” dose — capturing most of the weight-loss effect at lower nausea burden — while 15 mg is the maximum-effect comparator arm.

5. Response-rate distributions

SURMOUNT-1 15 mg arm distribution at week 72:

• Weight loss ≥30%: ~15%
• 25-30%: ~21%
• 20-25%: ~21%
• 15-20%: ~13%
• 10-15%: ~13%
• 5-10%: ~8%
• 0-5%: ~5%
• No loss or gain: ~4%

Roughly 15% of 15 mg recipients achieve ≥30% weight loss — comparable to post-bariatric-surgery outcomes at 1-2 years. Only ~4% have no response, lower than semaglutide’s ~6%.

6. SURMOUNT-2 — T2DM cohort

SURMOUNT-2 randomised 938 adults with T2DM and obesity to tirzepatide 10 mg, 15 mg, or placebo for 72 weeks.

72-week results:

• Tirzepatide 10 mg: −12.8%
• Tirzepatide 15 mg: −14.7%
• Placebo: −3.2%

As with semaglutide (STEP-2 vs STEP-1), T2DM cohort shows attenuated weight loss (~5-6 percentage points less) compared to non-diabetic cohort. The pattern is consistent with GLP-1 class behaviour.

7. SURMOUNT-3 — intensive behavioural therapy

SURMOUNT-3 tested tirzepatide after a 12-week intensive lifestyle intervention lead-in. 806 adults completed a 12-week low-calorie-diet + IBT lead-in (mean loss 6.9%), then were randomised to tirzepatide titrated to maximum tolerated (10 or 15 mg) or placebo for 72 additional weeks.

Cumulative 84-week results:

• Tirzepatide arm: additional −21.1% over 72 weeks; cumulative −26.6% from baseline
• Placebo arm: +3.3% regain over 72 weeks; cumulative −3.8% from baseline

−26.6% cumulative weight loss was the largest weight-loss result published from any pharmacotherapy obesity trial at the time of its 2023 publication. It has since been matched or exceeded only by triple-agonist retatrutide in Phase 2 (still to confirm in Phase 3).

8. SURMOUNT-4 — withdrawal trial

SURMOUNT-4 is the tirzepatide equivalent of STEP-4. 670 participants completed a 36-week open-label lead-in with tirzepatide titrated to maximum tolerated dose, then were randomised to continue tirzepatide or switch to placebo for 52 weeks.

Results (week 36 to week 88):

• Continuing-tirzepatide arm: additional −5.5%; cumulative from baseline −25.3%
• Switched-to-placebo arm: +14.0% regain; cumulative from baseline −9.9%

Regain after tirzepatide withdrawal (~14 percentage points) is larger in absolute terms than semaglutide withdrawal (~7 percentage points in STEP-4), because the starting loss is larger. The proportional regain is similar (~55-60% of lost weight regained over ~12 months post-withdrawal).

9. SURMOUNT-5 — head-to-head vs semaglutide

SURMOUNT-5 results summary (covered in detail in our tirzepatide vs semaglutide comparison reference):

• 72-week weight change: tirzepatide −20.2%, semaglutide −13.7% (treatment difference −6.5 pp, p < 0.001)
• First randomised head-to-head demonstration of dual-incretin superiority over single-incretin pharmacology

10. SURMOUNT-OSA — obstructive sleep apnoea

SURMOUNT-OSA (Malhotra et al, NEJM 2024) randomised 469 adults with moderate-to-severe obstructive sleep apnoea and obesity to tirzepatide 10 or 15 mg or placebo for 52 weeks. Primary endpoint: apnoea-hypopnoea index (AHI).

52-week results:

• AHI reduction: tirzepatide pooled −25.3 events/hour, placebo −5.3 events/hour
• Weight change: tirzepatide pooled −17.7%, placebo −1.6%
• OSA remission (AHI <5): tirzepatide ~42% (pooled), placebo ~15%

SURMOUNT-OSA is the first GLP-1/GIP agonist trial with a sleep-apnoea primary endpoint, and one of the first pharmacotherapies to approach CPAP-level AHI reduction in a pharmacologic approach.

11. Body composition — lean vs fat mass

SURMOUNT-1 DEXA sub-study body-composition at week 72 (15 mg arm):

• Total body weight loss: ~−22 kg
• Total body fat mass loss: ~−16 kg (~73% of total)
• Lean body mass loss: ~−6 kg (~27% of total)
• Visceral adipose tissue loss: disproportionately greater than subcutaneous
• Bone mineral density: modest decrease, within age-expected variability

The fat : lean ratio is broadly similar to semaglutide (~80 : 20 for sema, ~73 : 27 for tirz) and to dietary weight loss. Lean-mass preservation is an active research area, with bimagrumab + tirzepatide (BELIEVE-tirzepatide) showing improved body composition in early trials.

12. Is there a plateau at 72 weeks?

The SURMOUNT-1 15 mg curve is still sloping downward at week 72. Extrapolation suggests continued loss for a further 20-40 weeks would produce an additional 2-4 percentage points of loss (to ~−22% to −24%), before approaching plateau. SURMOUNT-4 lead-in data (36 weeks) and SURMOUNT-3 data (84 weeks cumulative) are consistent with this extrapolation.

A dedicated 2-year extension equivalent to STEP-5 has not been published as of 2026, but SURMOUNT-4’s continuing arm (88 weeks total) showed −25.3% cumulative from baseline, confirming the trajectory.

13. UK research protocol design implications

• Primary endpoint: 72 weeks is the standard duration; nadir not reached at 72 weeks so primary endpoint captures ongoing weight loss
• Shorter studies: 24 weeks captures ~55% of eventual 72-week loss; 36 weeks ~70%; 52 weeks ~85%
• Dose selection: 15 mg for maximum effect; 10 mg for efficient effect (captures ~93% of 15 mg effect at lower nausea); 5 mg for entry dose and dose-response anchor
• Titration period: 20 weeks from 2.5 mg to 15 mg with 4-week steps
• Measurement cadence: weight weekly for first 20 weeks (titration), then every 4 weeks
• Body composition: DEXA at baseline, 24 weeks, 48 weeks, 72 weeks
• Comparator arm: semaglutide 2.4 mg is the standard reference for head-to-head pharmacology; placebo for mechanistic isolation
• Population: non-diabetic cohort for cleanest weight signal; T2DM cohort adds ~5-6 pp attenuation

FAQ

How much more does tirzepatide produce vs semaglutide?
Approximately 6-7 percentage points more at maximum doses over 68-72 weeks (SURMOUNT-5 head-to-head: −20.2% vs −13.7%).

Does tirzepatide plateau like semaglutide?
Later and less sharply. Semaglutide plateau approaches ~week 60-68; tirzepatide is still losing at week 72. Long-term plateau likely occurs around week 90-100 based on extrapolation.

What weight loss can a participant expect on tirzepatide 15 mg?
Mean −20.9% at 72 weeks. Distribution: ~15% achieve ≥30%, ~36% achieve ≥25%, ~57% achieve ≥20%, ~83% achieve ≥10%. Only ~4% have no response.

What happens after stopping tirzepatide?
SURMOUNT-4 showed ~14 percentage points regain over 52 weeks after withdrawal — similar proportional regain to semaglutide (~55-60% of lost weight regained).

Why is tirzepatide better than semaglutide?
Best current evidence: dual GLP-1/GIP receptor agonism produces synergistic effects on appetite, adipose tissue biology and metabolic rate. GIP-R engagement at hypothalamic sites may also blunt GLP-1-driven nausea, allowing higher effective exposure.

What is SURMOUNT-3’s −26.6% cumulative loss?
12-week IBT lead-in produced −6.9%, then 72 weeks of tirzepatide added −21.1% to give −26.6% total at 84 weeks. Approaches post-bariatric-surgery outcomes.

Does tirzepatide cause more muscle loss than semaglutide?
No meaningful difference in fat:lean composition. Because tirzepatide produces more total weight loss, absolute lean-mass loss is larger in absolute terms, but proportional to total loss.

References

1. Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med 2022;387:205–216.
2. Garvey WT et al. Tirzepatide once weekly for treatment of obesity in people with type 2 diabetes (SURMOUNT-2). Lancet 2023;402:613–626.
3. Wadden TA et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity (SURMOUNT-3). Nat Med 2023;29:2909–2918.
4. Aronne LJ et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity (SURMOUNT-4). JAMA 2024;331:38–48.
5. Aronne LJ et al. Tirzepatide vs semaglutide in adults with obesity (SURMOUNT-5). N Engl J Med 2025 (pre-publication; topline 2024).
6. Malhotra A et al. Tirzepatide for treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA). N Engl J Med 2024;391:1193–1205.
7. Loomba R et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis (SYNERGY-NASH). N Engl J Med 2024;391:299–310.
8. Frías JP et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2). N Engl J Med 2021;385:503–515.
9. Coskun T et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab 2018;18:3–14.
10. Gasbjerg LS et al. GIP receptor agonism as a therapeutic strategy for obesity and type 2 diabetes. Nat Rev Endocrinol 2023;19:201–216.

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