The evidence.

The studies behind the figures on this site.

On this page
  1. Real-world discontinuation
  2. Tolerability and dose
  3. Stopping and regain
  4. Body composition
  5. Lower-dose approaches
  6. What the tablets take off
  7. Emerging, and not yet published
Westwood Road Health Centre, Reading.

1. Staying on treatment

Trial participants had free medication, close follow-up and support. Outside trials, more people stop and average weight loss is lower.

In a Cleveland Clinic cohort of 7,881 adults on semaglutide or tirzepatide injections, over half stopped within a year. Average weight loss at one year was 8.7%, against 14.9% to 20.9% in the trials. Those who stayed on treatment lost 11.9%.1

A Danish national study of 77,310 adults found 52% stopped within a year,2 and a US cohort of 125,474 showed the same pattern.3 In a Danish cohort of 110,749 people, only 12% had reached the target dose by their fifth prescription.4

2. Side effects and dose

In SURMOUNT-1, gastrointestinal events were the most common adverse effects, generally mild to moderate, and concentrated during dose escalation.5

Vomiting and diarrhoea rise with dose. Nausea peaks at 10mg, and constipation is lowest at 15mg.

Participants reporting each event in SURMOUNT-1, by maintenance dose
Event5mg10mg15mg
Nausea24.6%33.3%31.0%
Diarrhoea18.7%21.2%23.0%
Vomiting8.3%10.7%12.2%
Constipation16.8%17.1%11.7%

A pooled analysis across SURMOUNT-1 to -4 found discontinuation because of gastrointestinal events ranged from 1.0% to 10.5%, occurring principally during escalation.6

3. Stopping and regain

−5.5%

further average loss for those who continued tirzepatide for 52 more weeks in SURMOUNT-4.

+14.0%

regained by those switched to placebo over the same period.

89.5%

of the continuing group still held at least 80% of their loss at week 88, against 16.6% on placebo.

SURMOUNT-4 randomised 670 people who had completed 36 weeks of tirzepatide to continue or switch to placebo for a further 52 weeks.7

In a follow-up analysis of 308 people switched to placebo after losing at least 10%, most regained a quarter or more within a year and lost much of their improvement in waist size, triglycerides, cholesterol and insulin. Those who regained less kept these gains.8

4. Body composition

In the SURMOUNT-1 sub-study, about 75% of the weight lost was fat and 25% lean mass, the same proportion as placebo.9

Some lean tissue loss comes with any substantial weight loss. Losing weight more slowly hasn’t been shown to preserve more, and no study has tested whether lower doses do.

5. Lower-dose approaches

No randomised trial has tested below-licence dosing on its own, and it isn’t in clinical guidelines. The American Association of Clinical Endocrinology recommends approved dosing, but says lower doses may be considered for severe side effects or strong responders. Evidence on less frequent dosing is limited to case series and modelling.12 More on off-label prescribing.

Limits of the evidence

  • A lower dose giving the same weight loss as the maximum dose. Not shown: higher doses produced greater average loss.
  • Any dosing approach preserving muscle. Not established.
  • Benefits for metabolic health, inflammation, longevity or energy. Evidence is anecdotal.

6. Tablets

ATTAIN-1 compared placebo with three daily doses of orforglipron in 3,127 adults without diabetes, over 72 weeks.10

Average weight loss was 7.8% on 6mg, 9.3% on 12mg and 12.4% on 36mg, against 2.1% on placebo. Side effects were the mild to moderate gastrointestinal symptoms familiar from the rest of this class.

Weight loss rises with dose. The highest tablet dose averages well below the 20.2% seen with tirzepatide in a head-to-head trial.

A tablet may still suit someone who prefers not to inject, or who is maintaining a loss.

Emerging, and not yet published

Announced by the manufacturer. Not yet peer reviewed.

A daily tablet for maintenance after an injection

ATTAIN-MAINTAIN followed 376 people at a plateau on semaglutide or tirzepatide for 52 weeks after switching to daily orforglipron or placebo.

At 24 weeks, those switching from semaglutide averaged −0.1kg (placebo +9.4kg), and those from tirzepatide +2.6kg (placebo +9.1kg).11

The placebo group regained about 9kg in six months. The switch held better from semaglutide than from tirzepatide.

References

  1. Gasoyan H, Butsch WS, Schulte R, et al. Obesity (Silver Spring). 2025;33(9):1657–1667.
  2. Mailhac A, Pedersen L, Petersen I, Pottegård A, Sørensen HT, Thomsen RW. EASD Annual Meeting, Vienna, September 2025. Conference presentation.
  3. Rodriguez PJ, Zhang V, Gratzl S, et al. JAMA Network Open. 2025;8(1):e2457349.
  4. Thomsen RW, Mailhac A, Løhde JB, Pottegård A. Diabetes, Obesity and Metabolism. 2025;27(Suppl 2):66–88.
  5. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). New England Journal of Medicine. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
  6. Rubino D, et al. Diabetes, Obesity and Metabolism. 2025. doi:10.1111/dom.16176
  7. Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. doi:10.1001/jama.2023.24945
  8. Horn DB, Linetzky B, Davies MJ, et al. Cardiometabolic parameter change by weight regain on tirzepatide withdrawal in adults with obesity: a post hoc analysis of the SURMOUNT-4 trial. JAMA Internal Medicine. Published online 24 November 2025. doi:10.1001/jamainternmed.2025.6112
  9. Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes, Obesity and Metabolism. 2025;27(5):2720-2729. doi:10.1111/dom.16275
  10. Wharton S, Aronne LJ, Stefanski A, et al., for the ATTAIN-1 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment. New England Journal of Medicine. 2025;393(18). doi:10.1056/NEJMoa2511774. ClinicalTrials.gov NCT05869903
  11. Eli Lilly and Company. ATTAIN-MAINTAIN topline results, announced 18 December 2025. ClinicalTrials.gov NCT06584916. Not yet published in a peer-reviewed journal.
  12. Wu CC, Cengiz A, Lawley SD. Obesity. 2025;33(7):1232–1236.

Last reviewed: August 2026 · Reviewed by Dr Zubair Ahmed, GMC 6157380 · Next review due: August 2027