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D2C Peptides

Research goal

Tirzepatide and weight loss

Tirzepatide is the active ingredient in Zepbound, which FDA approved in November 2023 for chronic weight management in adults with obesity, or overweight plus a weight-related condition.12 In a 72-week trial of 2,539 adults, average weight fell 15.0% to 20.9% versus 3.1% on placebo.345 Stopping treatment led to substantial weight regain.619

This page summarizes published sources for information only. It is not medical advice and does not tell anyone to use a product. Questions about your own health belong with a licensed clinician. For questions about an order or a product, contact us.

What sources report

The weight evidence comes from the SURMOUNT trials of the once-weekly injectable. Each compared tirzepatide with placebo or with another drug over a year or more.768

Trials at a glance

Trial Who Length Average weight result
SURMOUNT-1 2,539 adults with obesity or overweight, without diabetes3 72 weeks7 15.0% to 20.9% lower, vs 3.1% on placebo45
SURMOUNT-1, three years 1,032 of them with prediabetes3 176 weeks3 12.3% to 19.7% lower, vs 1.3% on placebo9
SURMOUNT-4 670 adults after a 36-week lead-in10 88 weeks6 A further 5.5% lower if continued; 14.0% regained on placebo6
SURMOUNT-5 751 adults without type 2 diabetes811 72 weeks11 20.2% lower, vs 13.7% with semaglutide8
SURMOUNT-MAINTAIN 378 adults randomized at week 6012 112 weeks13 21.9% (full dose), 16.6% (5 mg) and 9.9% (placebo) below baseline1314

SURMOUNT-1: the main trial

Adults with obesity, or overweight with a weight-related condition, and without diabetes received tirzepatide 5, 10 or 15 mg or placebo once weekly.73 Treatment lasted 72 weeks, including 20 weeks of dose increases.7 Average weight fell 15.0% on 5 mg, 19.5% on 10 mg and 20.9% on 15 mg, versus 3.1% on placebo.45 On the two higher doses, 50% and 57% of participants lost at least 20% of their body weight, versus 3% on placebo.15 All prespecified heart and metabolic measures improved.16 Most side effects were mild to moderate stomach and bowel effects, mainly during dose increases.16 The authors described the weight reductions as substantial and sustained; the trial was supported by Eli Lilly.17

Three years, and diabetes prevention

In the 1,032 participants who also had prediabetes, treatment continued for 176 weeks.3 Average weight fell 12.3% on 5 mg, 18.7% on 10 mg and 19.7% on 15 mg, versus 1.3% on placebo.9 Type 2 diabetes was diagnosed in 1.3% on tirzepatide versus 13.3% on placebo.18 The blood sugar side of this trial is on Tirzepatide and blood sugar.

What happens after stopping

In SURMOUNT-4, 670 adults who completed a 36-week open-label lead-in on tirzepatide were randomized to continue it or switch to placebo.10 They averaged 48 years of age, 71% were women, and their average weight loss in the lead-in was 20.9%.10 Over the next 52 weeks, those who continued lost a further 5.5%, while those on placebo regained 14.0% of body weight.6 The authors concluded that withdrawing tirzepatide led to substantial regain.19

Stepping down instead of stopping

SURMOUNT-MAINTAIN, a 2026 trial in US adults with obesity, first treated participants at their maximum tolerated dose of 10 or 15 mg for 60 weeks.1213 It then randomized 378 of them to stay on that dose, drop to 5 mg, or switch to placebo.12 At week 112, modeled average weight was 21.9% below baseline on the full dose, 16.6% on 5 mg and 9.9% on placebo.1314 The authors suggested a lower dose might be an alternative to stopping, while noting that responses vary.20

In people with type 2 diabetes

Weight also fell in the diabetes trials. In SURPASS-1, 478 adults lost 7.0 to 9.5 kg over 40 weeks.2122 In SURPASS-2, weight loss on tirzepatide was 1.9 to 5.5 kg greater than on semaglutide 1 mg.23 Weight is not a labeled use of Mounjaro in the US.2425

Compared with semaglutide

SURMOUNT-5 compared tirzepatide at its maximum tolerated dose (10 or 15 mg) with semaglutide at 1.7 or 2.4 mg for 72 weeks.11 Average weight fell 20.2% versus 13.7%, and waist circumference fell 18.4 cm versus 13.0 cm.826 The other drug's evidence is on Semaglutide and weight loss.

How it lowers weight

  • Appetite: tirzepatide lowers calorie intake, likely by acting on appetite.27 GIP and GLP-1 receptors sit in brain areas that regulate appetite, and animal studies show the drug reaches and activates neurons there.28
  • Stomach emptying: it slows stomach emptying, with the largest effect after the first dose.29
  • What is lost: the Zepbound label says the weight lost involves more fat mass than lean mass.27
  • In mice: tested as LY3298176, it caused more weight loss than semaglutide, mostly through loss of fat.30

What the label says

  • Approved use: Zepbound is approved to reduce excess body weight and keep it off long term in adults with obesity, or with overweight and at least one weight-related condition.31 FDA defined these as a BMI of 30 or more, or 27 or more with a weight-related condition.2
  • Dosing: treatment starts at 2.5 mg once weekly for 4 weeks, then 5 mg.3233 Maintenance doses for weight are 5, 10 or 15 mg weekly, and 15 mg is the maximum.3435 The prescriber sets the dose; details are on Tirzepatide dosage.
  • Side effects: in the weight-reduction trials, 56% had stomach or bowel effects versus 30% on placebo.36 Between 4.8% and 6.7% stopped treatment because of side effects.37 In a weight-reduction trial of people with type 2 diabetes, low blood sugar occurred in 4.2% versus 1.3% on placebo.38 Full list: Tirzepatide side effects.
  • Limits: the label advises against combining it with other tirzepatide products or any GLP-1 receptor agonist.39 It says weight loss offers no benefit in pregnancy, and that Zepbound is stopped when a pregnancy is recognized.40
  • Mounjaro in the EU: Mounjaro is also used there to help adults lose weight and keep it under control.41

The brand page is What is Zepbound?, and the compound profile is What is Tirzepatide?.

Research-labeled tirzepatide and weight loss

FDA's page on unapproved GLP-1 drugs used for weight loss says companies have sold tirzepatide falsely labeled "for research purposes" or "not for human consumption".42 It says these products reached consumers for human use with dosing instructions, and calls them of unknown quality and possibly harmful.43 By May 31, 2026, FDA had also received more than 730 adverse event reports linked to compounded tirzepatide.44 The trial results on this page come from the approved injectable and cannot be assumed to apply to such products.43

Other compounds studied for weight are mapped on Peptides and weight loss and GLP-1 and weight loss.

Read next

More goal pages

Frequently asked questions

How long does it take to lose 20 lbs on tirzepatide?

The trials do not answer that directly. They report average percent changes at fixed time points, and results vary by person. In SURMOUNT-1, doses were raised over 20 weeks, and average weight at 72 weeks was 15.0% to 20.9% lower, versus 3.1% on placebo.745 How many pounds that means depends on starting weight. We found no sourced figure for pounds lost per month.

Will my doctor prescribe tirzepatide for weight loss?

That is a medical decision. As Zepbound, tirzepatide is approved for adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition.231 The labels also list cases where it should not be used, such as a personal or family history of medullary thyroid carcinoma or MEN 2.45 FDA advises getting a prescription from a doctor and filling it at a state-licensed pharmacy.46

Will I lose belly fat on tirzepatide?

Trials measured waist size rather than belly fat directly. In SURMOUNT-5, waist circumference fell 18.4 cm on tirzepatide versus 13.0 cm on semaglutide over 72 weeks.26 The Zepbound label says tirzepatide lowers weight with more fat mass loss than lean mass loss.27 No source for this page reported belly fat as a separate outcome, and results vary from person to person.

What happens to weight after stopping tirzepatide?

In SURMOUNT-4, adults who had lost an average 20.9% over 36 weeks were split into two groups.10 Those switched to placebo regained 14.0% of body weight over the next 52 weeks, while those who continued lost a further 5.5%.6 In SURMOUNT-MAINTAIN, stepping down to 5 mg kept more weight off than switching to placebo.14

Written by D2C Peptides Editorial Team.

Pending qualified review.

Updated .

Sources

  1. FDA Approves New Medication for Chronic Weight Management (news release). U.S. Food and Drug Administration, 2023.
  2. Same source as 1: eligible adults.
  3. Tirzepatide for Obesity Treatment and Diabetes Prevention (SURMOUNT-1, 3 years), PMID 39536238: methods. New England Journal of Medicine (via NLM PubMed E-utilities), 2025.
  4. SURMOUNT-1 abstract: weight change at 5 mg and 10 mg (PMID 35658024). New England Journal of Medicine (via NLM PubMed E-utilities), 2022.
  5. Same source as 4: weight change at 15 mg and placebo (PMID 35658024).
  6. SURMOUNT-4 abstract: randomized withdrawal results (PMID 38078870). JAMA (via NLM PubMed E-utilities), 2024.
  7. Same source as 4: Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1), PMID 35658024: methods.
  8. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5), PMID 40353578: weight. New England Journal of Medicine (via NLM PubMed E-utilities), 2025.
  9. Same source as 3: SURMOUNT-1 three-year abstract: weight (PMID 39536238).
  10. Same source as 6: Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity (SURMOUNT-4), PMID 38078870: lead-in.
  11. Same source as 8: SURMOUNT-5 abstract: methods (PMID 40353578).
  12. SURMOUNT-MAINTAIN abstract: randomization (PMID 42119587). The Lancet (via NLM PubMed E-utilities), 2026.
  13. Same source as 12: Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN), PMID 42119587: maximum tolerated dose arm.
  14. Same source as 12: 5 mg and placebo arms (PMID 42119587).
  15. Same source as 4: 20% or more weight reduction (PMID 35658024).
  16. Same source as 4: cardiometabolic measures and adverse events (PMID 35658024).
  17. Same source as 4: conclusions and funding (PMID 35658024).
  18. Same source as 3: SURMOUNT-1 three-year abstract: diabetes diagnoses (PMID 39536238).
  19. Same source as 6: conclusions (PMID 38078870).
  20. Same source as 12: interpretation (PMID 42119587).
  21. MOUNJARO Prescribing Information, revised 08/2026: SURPASS-1 design. U.S. Food and Drug Administration (label for Eli Lilly and Company), 2026.
  22. SURPASS-1 abstract: body weight (PMID 34186022). The Lancet (via NLM PubMed E-utilities), 2021.
  23. SURPASS-2 abstract: noninferiority, superiority and weight (PMID 34170647). New England Journal of Medicine (via NLM PubMed E-utilities), 2021.
  24. Same source as 21: MOUNJARO (tirzepatide) US Prescribing Information, revised 08/2026: Indications (type 2 diabetes).
  25. Same source as 21: Indications (cardiovascular risk).
  26. Same source as 8: SURMOUNT-5 abstract: waist circumference (PMID 40353578).
  27. ZEPBOUND Prescribing Information, revised 08/2026: Pharmacodynamics (body composition, calorie intake). U.S. Food and Drug Administration (label for Eli Lilly and Company), 2026.
  28. Same source as 27: Mechanism of action (appetite).
  29. Same source as 21: Gastric emptying.
  30. Coskun et al. 2018, mouse weight loss results. Molecular Metabolism, 2018.
  31. Same source as 27: ZEPBOUND (tirzepatide) US Prescribing Information, revised 08/2026: Indications (weight).
  32. Same source as 27: Starting dosage.
  33. Same source as 27: Dose escalation.
  34. Same source as 27: Maintenance dosage.
  35. Same source as 27: Maximum dosage.
  36. Same source as 27: Gastrointestinal adverse reactions.
  37. Same source as 27: Discontinuations.
  38. Same source as 27: Hypoglycemia.
  39. Same source as 27: Indications (OSA) and limitations of use.
  40. Same source as 27: Pregnancy.
  41. Mounjaro: EPAR overview (weight). European Medicines Agency, 2026.
  42. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss: research-labeled products. U.S. Food and Drug Administration, 2026.
  43. Same source as 42: consumer warning.
  44. Same source as 42: FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss (content current as of 10/01/2026): adverse event reports.
  45. Same source as 21: Contraindications.
  46. Same source as 42: recommendations.