Weight Regain Trajectories After Discontinuation of Semaglutide or Tirzepatide: A Reconstructed Aggregate-Data Bayesian Longitudinal Meta-Analysis.

Kow CS, Thiruchelvam K, Ramachandram DS, Zaihan AF

Endocrinology, diabetes & metabolism1 Sept 2026

PMID42673571PMCIDPMC13529306DOI10.1002/edm2.70325PepBankPUB-42673571

Summary

BackgroundSemaglutide and tirzepatide produce substantial weight loss during treatment, but the trajectory of weight regain after discontinuation remains uncertain.ObjectiveTo estimate post-discontinuation weight-regain trajectories and explore predictors of faster regain.MethodsWe used published timepoint-level aggregate data from studies evaluating weight change after discontinuation of semaglutide or tirzepatide to perform a Bayesian hierarchical longitudinal re-analysis. The model estimated weight loss at cessation, monthly regain rate, time to 50% regain, and time to return to baseline weight. Bayesian meta-regression examined medication type, magnitude of initial weight loss, and post-discontinuation behavioural or lifestyle support. Longer-term estimates assumed a constant linear regain rate.ResultsSix studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks. Estimated weight loss at cessation was 15.35 kg (95% credible interval [CrI] 11.18-19.60), followed by regain of 1.04 kg/month (95% CrI 0.80-1.29). Based on the linear model, 50% of initial weight loss was projected to be regained by 7.50 months (95% CrI 5.05-10.57), with return to baseline weight by 15.00 months (95% CrI 10.10-21.13). Tirzepatide showed numerically faster regain than semaglutide in unadjusted analyses, but no clear independent drug-specific difference was evident after adjustment. Greater initial weight loss showed the strongest directional association with faster regain, although the credible interval included zero. Behavioural or lifestyle support was directionally associated with slower regain, but the estimate was imprecise.ConclusionsWeight regain after discontinuation of semaglutide or tirzepatide was rapid and clinically meaningful. Because estimates beyond 52 weeks were model-based extrapolations, they should be interpreted cautiously. Early monitoring and proactive maintenance planning may be warranted after treatment cessation.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

2 results from studies that gave the peptide. 2 results from people.

01HumanSystematic reviewEfficacy outcome
In a Bayesian meta-analysis, tirzepatide showed numerically faster weight regain than semaglutide after discontinuation in unadjusted analyses.
In plain wordsAfter stopping, tirzepatide showed numerically faster weight regain than semaglutide in unadjusted analyses, but the difference was not clearly real.
Peptide
Tirzepatide
Outcome
IncreaseWeight regain after discontinuation, unadjusted
Study
n: not reported in source
Comparator
Semaglutide
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Tirzepatide showed numerically faster regain than semaglutide in unadjusted analyses
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
Show in the study text Report a problemFND-4267357109
02HumanSystematic reviewEfficacy outcome
In a Bayesian meta-analysis, no clear independent difference in weight regain between tirzepatide and semaglutide was evident after adjustment.
In plain wordsAfter adjusting for other factors, there was no clear difference in weight regain between tirzepatide and semaglutide.
Peptide
Tirzepatide
Outcome
No significant changeWeight regain after discontinuation, adjusted
Study
n: not reported in source
Comparator
Semaglutide
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
but no clear independent drug-specific difference was evident after adjustment.
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
Show in the study text Report a problemFND-4267357110

Studies that did not test the peptide alone12

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

03HumanNot a test of Semaglutide aloneSystematic reviewMechanism
In a Bayesian meta-regression pooling semaglutide and tirzepatide arms, greater initial weight loss showed the strongest directional association with faster weight regain, although the credible interval included zero.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people who lost more weight at first tended to regain faster, but the estimate was imprecise.
Peptide
Semaglutide
Outcome
Not applicableInitial weight loss as predictor of regain (pooled)
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Greater initial weight loss showed the strongest directional association with faster regain, although the credible interval included zero.
1 context sentence(design, population, supporting numbers)
Summary · context
Bayesian meta-regression examined medication type, magnitude of initial weight loss, and post-discontinuation behavioural or lifestyle support.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4267357111
04HumanNot a test of Tirzepatide aloneSystematic reviewMechanism
In a Bayesian meta-regression pooling semaglutide and tirzepatide arms, greater initial weight loss showed the strongest directional association with faster weight regain, although the credible interval included zero.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people who lost more weight at first tended to regain faster, but the estimate was imprecise.
Peptide
Tirzepatide
Outcome
Not applicableInitial weight loss as predictor of regain (pooled)
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Greater initial weight loss showed the strongest directional association with faster regain, although the credible interval included zero.
1 context sentence(design, population, supporting numbers)
Summary · context
Bayesian meta-regression examined medication type, magnitude of initial weight loss, and post-discontinuation behavioural or lifestyle support.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4267357112
05HumanNot a test of Semaglutide aloneSystematic reviewMechanism
In a Bayesian meta-regression pooling semaglutide and tirzepatide arms, behavioural or lifestyle support was directionally associated with slower weight regain, but the estimate was imprecise.
In plain wordsAcross studies of semaglutide and tirzepatide combined, support with behaviour or lifestyle tended to go with slower weight regain, but the estimate was imprecise.
Peptide
Semaglutide
Outcome
Not applicableBehavioural or lifestyle support as predictor of regain (pooled)
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Behavioural or lifestyle support was directionally associated with slower regain, but the estimate was imprecise.
1 context sentence(design, population, supporting numbers)
Summary · context
Bayesian meta-regression examined medication type, magnitude of initial weight loss, and post-discontinuation behavioural or lifestyle support.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4267357113
06HumanNot a test of Tirzepatide aloneSystematic reviewMechanism
In a Bayesian meta-regression pooling semaglutide and tirzepatide arms, behavioural or lifestyle support was directionally associated with slower weight regain, but the estimate was imprecise.
In plain wordsAcross studies of semaglutide and tirzepatide combined, support with behaviour or lifestyle tended to go with slower weight regain, but the estimate was imprecise.
Peptide
Tirzepatide
Outcome
Not applicableBehavioural or lifestyle support as predictor of regain (pooled)
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
Behavioural or lifestyle support was directionally associated with slower regain, but the estimate was imprecise.
1 context sentence(design, population, supporting numbers)
Summary · context
Bayesian meta-regression examined medication type, magnitude of initial weight loss, and post-discontinuation behavioural or lifestyle support.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4267357114
07HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, estimated weight loss at treatment cessation was 15.35 kg.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people had lost about 15.35 kg when treatment stopped.
Peptide
Semaglutide
Outcome
DecreaseEstimated weight loss at cessation (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Weight loss at cessation
15.35 kg
pooled semaglutide and tirzepatide
Source sentences
Summary
Estimated weight loss at cessation was 15.35 kg (95% credible interval [CrI] 11.18-19.60)
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4267357101
08HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, estimated weight loss at treatment cessation was 15.35 kg.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people had lost about 15.35 kg when treatment stopped.
Peptide
Tirzepatide
Outcome
DecreaseEstimated weight loss at cessation (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Weight loss at cessation
15.35 kg
pooled semaglutide and tirzepatide
Source sentences
Summary
Estimated weight loss at cessation was 15.35 kg (95% credible interval [CrI] 11.18-19.60)
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4267357102
09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, weight regain after discontinuation was 1.04 kg per month.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people regained about 1.04 kg per month after stopping.
Peptide
Semaglutide
Outcome
IncreaseMonthly weight regain rate after discontinuation (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Weight regain rate
1.04 kg/month
pooled semaglutide and tirzepatide
Source sentences
Summary
followed by regain of 1.04 kg/month (95% CrI 0.80-1.29).
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4267357103
10HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, weight regain after discontinuation was 1.04 kg per month.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people regained about 1.04 kg per month after stopping.
Peptide
Tirzepatide
Outcome
IncreaseMonthly weight regain rate after discontinuation (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Weight regain rate
1.04 kg/month
pooled semaglutide and tirzepatide
Source sentences
Summary
followed by regain of 1.04 kg/month (95% CrI 0.80-1.29).
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4267357104
11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, 50% of initial weight loss was projected to be regained by 7.50 months.
In plain wordsAcross studies of semaglutide and tirzepatide combined, half of the lost weight was projected to return by about 7.5 months.
Peptide
Semaglutide
Outcome
IncreaseProjected time to 50% regain (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Time to 50% regain
7.5 months
pooled semaglutide and tirzepatide
Source sentences
Summary
Based on the linear model, 50% of initial weight loss was projected to be regained by 7.50 months (95% CrI 5.05-10.57)
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4267357105
12HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, 50% of initial weight loss was projected to be regained by 7.50 months.
In plain wordsAcross studies of semaglutide and tirzepatide combined, half of the lost weight was projected to return by about 7.5 months.
Peptide
Tirzepatide
Outcome
IncreaseProjected time to 50% regain (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Time to 50% regain
7.5 months
pooled semaglutide and tirzepatide
Source sentences
Summary
Based on the linear model, 50% of initial weight loss was projected to be regained by 7.50 months (95% CrI 5.05-10.57)
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4267357106
13HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, return to baseline weight was projected by 15.00 months.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people were projected to be back at their starting weight by about 15 months.
Peptide
Semaglutide
Outcome
IncreaseProjected time to return to baseline weight (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Time to baseline weight
15 months
pooled semaglutide and tirzepatide
Source sentences
Summary
with return to baseline weight by 15.00 months (95% CrI 10.10-21.13).
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4267357107
14HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In a Bayesian meta-analysis pooling semaglutide and tirzepatide arms, return to baseline weight was projected by 15.00 months.
In plain wordsAcross studies of semaglutide and tirzepatide combined, people were projected to be back at their starting weight by about 15 months.
Peptide
Tirzepatide
Outcome
IncreaseProjected time to return to baseline weight (pooled)
Study
n = 1,776
Outcome group
Body weight · Metabolic and weight
Measurements
Time to baseline weight
15 months
pooled semaglutide and tirzepatide
Source sentences
Summary
with return to baseline weight by 15.00 months (95% CrI 10.10-21.13).
1 context sentence(design, population, supporting numbers)
Summary · context
Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4267357108

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 3Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 2
9 Oct 2026, 03:07 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.