Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial.

Horn DB, Linetzky B, Davies MJ, Laffin LJ, Wang H, Murphy MA, Zimner-Rapuch S, Lau E, Arad AD, Lee CJ

JAMA internal medicine1 Feb 2026Cited by 32 (Europe PMC)

PMID41284285PMCIDPMC12645400DOI10.1001/jamainternmed.2025.6112PepBankPUB-41284285

Read at source PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: CC BY-NC-ND. Results still quote short attributed sentences.

Results from this study10

10 results from studies that gave the peptide. 10 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity, weight decreased during the first 36 weeks of tirzepatide treatment.
In plain wordsIn adults with obesity, weight went down during the first 36 weeks of tirzepatide.
Peptide
Tirzepatide
Outcome
DecreaseBody weight during 36 weeks of tirzepatide
Study
n = 308
Outcome group
Body weight · Metabolic and weight
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Source sentences
Summary
During the initial 36 weeks of tirzepatide treatment, participants' weight decreased
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428501
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity, cardiometabolic parameters improved during the first 36 weeks of tirzepatide treatment.
In plain wordsIn adults with obesity, heart and metabolic measures improved during the first 36 weeks of tirzepatide.
Peptide
Tirzepatide
Outcome
MixedCardiometabolic parameters during 36 weeks of tirzepatide
Study
n = 308
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Source sentences
Summary
cardiometabolic parameters improved.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428502
03HumanRandomized controlled trialEfficacy outcome
After tirzepatide withdrawal, waist circumference increased more with greater weight regain (0.8 cm in the less than 25% group to 14.7 cm in the 75% or more group).
In plain wordsAfter stopping tirzepatide, waist size grew more in people who regained more weight.
Peptide
Tirzepatide
Outcome
IncreaseWaist circumference change after withdrawal, by weight regain
Study
n = 308
Comparator
Weight regain category
Outcome group
Body weight · Metabolic and weight
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Measurements
waist change
0.8 cm
<25% regain
waist change
5.4 cm
25% to <50% regain
waist change
10.1 cm
50% to <75% regain
waist change
14.7 cm
>=75% regain
Source sentences
Summary
the mean change in waist circumference increased by weight regain category (<25% weight regain, 0.8 cm; 95% CI, -1.0 to 2.6; 25% to <50%, 5.4 cm; 95% CI, 4.0-6.8; 50% to <75%, 10.1 cm; 95% CI, 8.9-11.3; ≥75%, 14.7 cm; 95% CI, 12.7-16.7; P < .001)
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428503
04HumanRandomized controlled trialEfficacy outcome
After tirzepatide withdrawal, systolic blood pressure rose in all regain categories, with larger rises at greater regain.
In plain wordsAfter stopping tirzepatide, blood pressure rose, more so in people who regained more weight.
Peptide
Tirzepatide
Outcome
IncreaseSystolic blood pressure change after withdrawal, by weight regain
Study
n = 308
Comparator
Weight regain category
Outcome group
Blood pressure · Cardiovascular
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Measurements
SBP change
6.8 mm Hg
<25% regain
SBP change
7.3 mm Hg
25% to <50% regain
SBP change
9.6 mm Hg
50% to <75% regain
SBP change
10.4 mm Hg
>=75% regain
Source sentences
Summary
systolic blood pressure (6.8 mm Hg [95% CI, 3.9-9.7], 7.3 mm Hg [95% CI, 4.8-9.8], 9.6 mm Hg [95% CI, 7.1-12.1], and 10.4 mm Hg [95% CI, 8.0-12.8], respectively; P = .002)
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428504
05HumanRandomized controlled trialEfficacy outcome
After tirzepatide withdrawal, non-HDL cholesterol rose more with greater weight regain (from -0.4% to 10.8%).
In plain wordsAfter stopping tirzepatide, non-HDL cholesterol rose more in people who regained more weight.
Peptide
Tirzepatide
Outcome
IncreaseNon-HDL cholesterol change after withdrawal, by weight regain
Study
n = 308
Comparator
Weight regain category
Outcome group
Lipids · Cardiovascular
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Measurements
non-HDL cholesterol change
−0.4%
<25% regain
non-HDL cholesterol change
1.6%
25% to <50% regain
non-HDL cholesterol change
8.4%
50% to <75% regain
non-HDL cholesterol change
10.8%
>=75% regain
Source sentences
Summary
non-high-density lipoprotein cholesterol (-0.4% [95% CI, -7.3 to 6.5], 1.6% [95% CI, -2.3 to 5.5], 8.4% [95% CI, 3.9-12.9], and 10.8% [95% CI, 5.3-16.3]
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428505
06HumanRandomized controlled trialEfficacy outcome
After tirzepatide withdrawal, hemoglobin A1c rose more with greater weight regain (0.14% to 0.35%).
In plain wordsAfter stopping tirzepatide, HbA1c rose more in people who regained more weight.
Peptide
Tirzepatide
Outcome
IncreaseHemoglobin A1c change after withdrawal, by weight regain
Study
n = 308
Comparator
Weight regain category
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Measurements
HbA1c change
0.14%
<25% regain
HbA1c change
0.15%
25% to <50% regain
HbA1c change
0.27%
50% to <75% regain
HbA1c change
0.35%
>=75% regain
Source sentences
Summary
hemoglobin A1c (0.14% [95% CI, 0.06-0.22], 0.15% [95% CI, 0.09-0.21], 0.27% [95% CI, 0.21-0.33], and 0.35% [95% CI, 0.29-0.41], respectively; P < .001)
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428506
07HumanRandomized controlled trialEfficacy outcome
After tirzepatide withdrawal, fasting insulin changed by -4.0% with less than 25% weight regain, 15.4% with 25% to less than 50%, 46.2% with 50% to less than 75%, and 26.3% with 75% or more.
In plain wordsAfter stopping tirzepatide, fasting insulin rose most in people who regained 50% to under 75% of lost weight; the rise was not steady across groups.
Peptide
Tirzepatide
Outcome
MixedFasting insulin change after withdrawal, by weight regain
Study
n = 308
Comparator
Weight regain category
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Measurements
fasting insulin change
−4%
<25% regain
fasting insulin change
15.4%
25% to <50% regain
fasting insulin change
46.2%
50% to <75% regain
fasting insulin change
26.3%
>=75% regain
Source sentences
Summary
fasting insulin (-4.0% [95% CI, -20.7 to 12.7], 15.4% [95% CI, 2.3-28.5], 46.2% [95% CI, 29.5-62.9], and 26.3% [95% CI, 9.6-43.0]
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428507
08HumanRandomized controlled trialEfficacy outcome
In participants with less than 25% weight regain, waist circumference at week 88 was not significantly different from week 36.
In plain wordsIn people who regained little weight after stopping tirzepatide, waist size at week 88 matched week 36.
Peptide
Tirzepatide
Outcome
No significant changeWaist circumference at week 88 versus week 36, less than 25% regain
Study
n = 54
Comparator
Week 36
Outcome group
Body weight · Metabolic and weight
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Source sentences
Summary
Changes at week 88 in waist circumference, non-high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428508
09HumanRandomized controlled trialEfficacy outcome
In participants with less than 25% weight regain, non-HDL cholesterol at week 88 was not significantly different from week 36.
In plain wordsIn people who regained little weight after stopping tirzepatide, non-HDL cholesterol at week 88 matched week 36.
Peptide
Tirzepatide
Outcome
No significant changeNon-HDL cholesterol at week 88 versus week 36, less than 25% regain
Study
n = 54
Comparator
Week 36
Outcome group
Lipids · Cardiovascular
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Source sentences
Summary
Changes at week 88 in waist circumference, non-high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428509
10HumanRandomized controlled trialEfficacy outcome
In participants with less than 25% weight regain, fasting insulin at week 88 was not significantly different from week 36.
In plain wordsIn people who regained little weight after stopping tirzepatide, fasting insulin at week 88 matched week 36.
Peptide
Tirzepatide
Outcome
No significant changeFasting insulin at week 88 versus week 36, less than 25% regain
Study
n = 54
Comparator
Week 36
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mg or 15 mg (maximum tolerated dose) · 36 weeks of tirzepatide, then 52 weeks after withdrawalAs given in this study (human).
Source sentences
Summary
Changes at week 88 in waist circumference, non-high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36.
2 context sentences(design, population, supporting numbers)
Summary · context
This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo.
Summary · context
After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88).
Report a problemFND-4128428510

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04660643

A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight for the Maintenance of Weight Loss

Eli Lilly and Companyn = 78329 Mar 2021 to 18 May 2023

Obesity · Overweight

Trial page ClinicalTrials.govUpdated 22 May 2024

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 2Current
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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