Relationship of early rapid weight loss to efficacy and safety of tirzepatide and semaglutide for obesity: SURMOUNT-5 post hoc analysis.

Aronne LJ, Horn DB, Kokkinos AD, Falcon BL, Wang H, Hoffmann HT, Lee CJ, Dunn JP

The American journal of medicine20 Mar 2026Cited by 1 (Europe PMC)

PMID41865857DOI10.1016/j.amjmed.2026.03.010PepBankPUB-41865857

Publisher page PubMedAsk about this study

Summary

BackgroundA knowledge gap remains in how the rate of body weight reduction impacts efficacy and safety of obesity management medications. This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.MethodsRapid responders and non-rapid responders were defined as participants that obtained ≥ 15% and < 15% body weight reduction by Week 24, respectively. Baseline characteristics, and proportion of participants achieving body weight reduction thresholds by Week 72 were assessed. End-of-study safety and gastrointestinal adverse events measures were summarized.ResultsOverall, 32.3% were rapid responders (tirzepatide: 44%, semaglutide: 21%). The proportions of participants achieving body weight reduction thresholds by Week 72 were higher for rapid responders versus non-rapid responders. Safety trends for tirzepatide and semaglutide were similar between responder groups. A numerically higher number of gastrointestinal/hepatobiliary adverse events were reported in rapid responders. Study treatment completion was similar among rapid responders and non-rapid responders for both treatments.ConclusionsIn this post hoc analysis of SURMOUNT-5, a greater proportion of tirzepatide-treated participants in both responder groups achieved all body weight reduction thresholds versus semaglutide. Although rapid responders experienced more gastrointestinal/hepatobiliary adverse events in both treatments, this did not affect rates of study treatment completion relative to non-rapid responders.Trial registrationclinicaltrials.gov identifier NCT05822830.

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

Results from this study12

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

01HumanRandomized controlled trialEfficacy outcome
In adults with obesity in SURMOUNT-5, 44% of participants on tirzepatide were rapid responders, defined as at least 15% body weight reduction by Week 24.
In plain wordsIn adults with obesity, 44% of people on tirzepatide lost at least 15% of body weight by Week 24.
Peptide
Tirzepatide
Outcome
Not applicableRapid responders (≥15% weight reduction by Week 24)
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
Proportion of rapid responders
44%
tirzepatide
Source sentences
Summary
Overall, 32.3% were rapid responders (tirzepatide: 44%, semaglutide: 21%).
2 context sentences(design, population, supporting numbers)
Summary · context
Rapid responders and non-rapid responders were defined as participants that obtained ≥ 15% and < 15% body weight reduction by Week 24, respectively.
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585701
02HumanRandomized controlled trialEfficacy outcome
In adults with obesity in SURMOUNT-5, 21% of participants on semaglutide were rapid responders, defined as at least 15% body weight reduction by Week 24.
In plain wordsIn adults with obesity, 21% of people on semaglutide lost at least 15% of body weight by Week 24.
Peptide
Semaglutide
Outcome
Not applicableRapid responders (≥15% weight reduction by Week 24)
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
Proportion of rapid responders
21%
semaglutide
Source sentences
Summary
Overall, 32.3% were rapid responders (tirzepatide: 44%, semaglutide: 21%).
2 context sentences(design, population, supporting numbers)
Summary · context
Rapid responders and non-rapid responders were defined as participants that obtained ≥ 15% and < 15% body weight reduction by Week 24, respectively.
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585702
03HumanRandomized controlled trialSafety outcome
In adults with obesity, safety trends with tirzepatide were similar between rapid and non-rapid responders.
In plain wordsIn adults with obesity, tirzepatide safety trends were similar in rapid and non-rapid responders.
Peptide
Tirzepatide
Outcome
No significant changeSafety trends in rapid versus non-rapid responders
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Safety trends for tirzepatide and semaglutide were similar between responder groups.
1 context sentence(design, population, supporting numbers)
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585705
04HumanRandomized controlled trialSafety outcome
In adults with obesity, safety trends with semaglutide were similar between rapid and non-rapid responders.
In plain wordsIn adults with obesity, semaglutide safety trends were similar in rapid and non-rapid responders.
Peptide
Semaglutide
Outcome
No significant changeSafety trends in rapid versus non-rapid responders
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Safety trends for tirzepatide and semaglutide were similar between responder groups.
1 context sentence(design, population, supporting numbers)
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585706
05HumanRandomized controlled trialSafety outcome
In adults with obesity on tirzepatide, rapid responders had numerically more gastrointestinal and hepatobiliary adverse events than non-rapid responders.
In plain wordsIn adults with obesity on tirzepatide, rapid responders had slightly more stomach, gut and liver-related side effects than non-rapid responders.
Peptide
Tirzepatide
Outcome
IncreaseGastrointestinal/hepatobiliary adverse events in rapid responders
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
A numerically higher number of gastrointestinal/hepatobiliary adverse events were reported in rapid responders.
2 context sentences(design, population, supporting numbers)
Summary · context
Although rapid responders experienced more gastrointestinal/hepatobiliary adverse events in both treatments, this did not affect rates of study treatment completion relative to non-rapid responders.
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585707
06HumanRandomized controlled trialSafety outcome
In adults with obesity on semaglutide, rapid responders had numerically more gastrointestinal and hepatobiliary adverse events than non-rapid responders.
In plain wordsIn adults with obesity on semaglutide, rapid responders had slightly more stomach, gut and liver-related side effects than non-rapid responders.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal/hepatobiliary adverse events in rapid responders
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
A numerically higher number of gastrointestinal/hepatobiliary adverse events were reported in rapid responders.
2 context sentences(design, population, supporting numbers)
Summary · context
Although rapid responders experienced more gastrointestinal/hepatobiliary adverse events in both treatments, this did not affect rates of study treatment completion relative to non-rapid responders.
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585708
07HumanRandomized controlled trialSafety outcome
In adults with obesity on tirzepatide, study treatment completion was similar between rapid and non-rapid responders.
In plain wordsIn adults with obesity on tirzepatide, rapid and non-rapid responders finished treatment at similar rates.
Peptide
Tirzepatide
Outcome
No significant changeStudy treatment completion
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Study treatment completion was similar among rapid responders and non-rapid responders for both treatments.
1 context sentence(design, population, supporting numbers)
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585709
08HumanRandomized controlled trialSafety outcome
In adults with obesity on semaglutide, study treatment completion was similar between rapid and non-rapid responders.
In plain wordsIn adults with obesity on semaglutide, rapid and non-rapid responders finished treatment at similar rates.
Peptide
Semaglutide
Outcome
No significant changeStudy treatment completion
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
Study treatment completion was similar among rapid responders and non-rapid responders for both treatments.
1 context sentence(design, population, supporting numbers)
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585710
09HumanRandomized controlled trialEfficacy outcome
In adults with obesity, a greater proportion of tirzepatide-treated participants than semaglutide-treated participants achieved all body weight reduction thresholds in both responder groups.
In plain wordsIn adults with obesity, more people on tirzepatide than on semaglutide reached every weight loss target, in both rapid and non-rapid responders.
Peptide
Tirzepatide
Outcome
IncreaseParticipants achieving body weight reduction thresholds in both responder groups
Study
n: not reported in source
Comparator
Semaglutide
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
In this post hoc analysis of SURMOUNT-5, a greater proportion of tirzepatide-treated participants in both responder groups achieved all body weight reduction thresholds versus semaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585711
10HumanRandomized controlled trialEfficacy outcome
In adults with obesity, a smaller proportion of semaglutide-treated participants than tirzepatide-treated participants achieved all body weight reduction thresholds in both responder groups.
In plain wordsIn adults with obesity, fewer people on semaglutide than on tirzepatide reached every weight loss target, in both rapid and non-rapid responders.
Peptide
Semaglutide
Outcome
DecreaseParticipants achieving body weight reduction thresholds in both responder groups
Study
n: not reported in source
Comparator
Tirzepatide
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
In this post hoc analysis of SURMOUNT-5, a greater proportion of tirzepatide-treated participants in both responder groups achieved all body weight reduction thresholds versus semaglutide.
1 context sentence(design, population, supporting numbers)
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
Show in the study text Report a problemFND-4186585712

Studies that did not test the peptide alone2

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.

11HumanNot a test of Tirzepatide aloneRandomized controlled trialEfficacy outcome
In adults with obesity, pooled across tirzepatide and semaglutide, rapid responders reached body weight reduction thresholds by Week 72 more often than non-rapid responders.
In plain wordsIn adults with obesity on tirzepatide or semaglutide, rapid responders more often reached weight loss goals by Week 72 than non-rapid responders.
Peptide
Tirzepatide
Outcome
IncreaseBody weight reduction thresholds by Week 72, rapid versus non-rapid responders
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
The proportions of participants achieving body weight reduction thresholds by Week 72 were higher for rapid responders versus non-rapid responders.
2 context sentences(design, population, supporting numbers)
Summary · context
Baseline characteristics, and proportion of participants achieving body weight reduction thresholds by Week 72 were assessed.
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
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-4186585703
12HumanNot a test of Semaglutide aloneRandomized controlled trialEfficacy outcome
In adults with obesity, pooled across tirzepatide and semaglutide, rapid responders reached body weight reduction thresholds by Week 72 more often than non-rapid responders.
In plain wordsIn adults with obesity on tirzepatide or semaglutide, rapid responders more often reached weight loss goals by Week 72 than non-rapid responders.
Peptide
Semaglutide
Outcome
IncreaseBody weight reduction thresholds by Week 72, rapid versus non-rapid responders
Study
n: not reported in source
Comparator
Non-rapid responders
Outcome group
Body weight · Metabolic and weight
Source sentences
Summary
The proportions of participants achieving body weight reduction thresholds by Week 72 were higher for rapid responders versus non-rapid responders.
2 context sentences(design, population, supporting numbers)
Summary · context
Baseline characteristics, and proportion of participants achieving body weight reduction thresholds by Week 72 were assessed.
Summary · context
This SURMOUNT-5 post hoc analysis aimed to define rapid responders and evaluated efficacy and safety of tirzepatide versus. semaglutide in rapid responders versus non-rapid responders.
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-4186585704

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 postedNCT05822830

A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities

Eli Lilly and Companyn = 75121 Apr 2023 to 13 Nov 2024

Obesity · Overweight

Trial page ClinicalTrials.govUpdated 26 Nov 2025

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.

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