Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss.

Wharton S, Calanna S, Davies M, Dicker D, Goldman B, Lingvay I, Mosenzon O, Rubino DM, Thomsen M, Wadden TA, Pedersen SD

Diabetes, obesity & metabolism4 Oct 2021Cited by 135 (Europe PMC)

PMID34514682PMCIDPMC9293236DOI10.1111/dom.14551PepBankPUB-34514682

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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. Results still quote short attributed sentences.

Results from this study10

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

01HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity, gastrointestinal adverse events were more common with semaglutide 2.4 mg than with placebo.
In plain wordsIn adults with overweight or obesity, stomach and gut side effects were more common with semaglutide 2.4 mg than with placebo.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal adverse events overall
Study
n = 3,379
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Source sentences
Summary
GI AEs were more common with semaglutide 2.4 mg than placebo
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468201
02HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity, nausea occurred in 43.9% of participants on semaglutide 2.4 mg versus 16.1% on placebo.
In plain wordsIn adults with overweight or obesity, nausea was more common with semaglutide 2.4 mg than with placebo.
Peptide
Semaglutide
Outcome
IncreaseNausea
Study
n = 3,379
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Nausea incidence
43.9%
semaglutide 2.4 mg
Source sentences
Summary
nausea (43.9% vs. 16.1% of participants)
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468202
03HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity, diarrhoea occurred in 29.7% on semaglutide 2.4 mg versus 15.9% on placebo.
In plain wordsIn adults with overweight or obesity, diarrhoea was more common with semaglutide 2.4 mg than with placebo.
Peptide
Semaglutide
Outcome
IncreaseDiarrhoea
Study
n = 3,379
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Diarrhoea incidence
29.7%
semaglutide 2.4 mg
Source sentences
Summary
diarrhoea (29.7% vs. 15.9%)
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468203
04HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity, vomiting occurred in 24.5% on semaglutide 2.4 mg versus 6.3% on placebo.
In plain wordsIn adults with overweight or obesity, vomiting was more common with semaglutide 2.4 mg than with placebo.
Peptide
Semaglutide
Outcome
IncreaseVomiting
Study
n = 3,379
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Vomiting incidence
24.5%
semaglutide 2.4 mg
Source sentences
Summary
vomiting (24.5% vs. 6.3%)
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468204
05HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity, constipation occurred in 24.2% on semaglutide 2.4 mg versus 11.1% on placebo.
In plain wordsIn adults with overweight or obesity, constipation was more common with semaglutide 2.4 mg than with placebo.
Peptide
Semaglutide
Outcome
IncreaseConstipation
Study
n = 3,379
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Constipation incidence
24.2%
semaglutide 2.4 mg
Source sentences
Summary
constipation (24.2% vs. 11.1%)
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468205
06HumanRandomized controlled trialMechanism
In adults with overweight or obesity, mediation analysis found that less than 1 percentage point of the additional weight loss with semaglutide versus placebo was mediated by gastrointestinal adverse events.
In plain wordsIn adults with overweight or obesity, gut side effects explained very little of the extra weight loss with semaglutide compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeWeight loss mediated by GI adverse events
Study
n = 3,379
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Weight loss mediated by GI AEs
< 1 percentage point
semaglutide vs placebo
Additional weight loss vs placebo
7.6 to 14.4%
STEP 1-3
Source sentences
Summary
Consistent with this observation, mediation analysis found that GI AEs contributed little to semaglutide-induced WL: of the additional 7.6%-14.4% WL with semaglutide versus placebo, <1 percentage point was mediated by GI AEs.
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468209
07HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity on semaglutide, most gastrointestinal adverse events were non-serious (99.5%) and mild-to-moderate (98.1%), and were transient.
In plain wordsIn adults with overweight or obesity on semaglutide, nearly all gut side effects were non-serious and mild-to-moderate, and passed.
Peptide
Semaglutide
Outcome
Not applicableSeriousness and severity of GI adverse events
Study
n = 2,117
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Non-serious GI AEs
99.5%
semaglutide
Mild-to-moderate GI AEs
98.1%
semaglutide
Source sentences
Summary
Most GI AEs with semaglutide were non-serious (99.5% of AEs), mild-to-moderate (98.1%), transient and occurred most frequently during/shortly after dose escalation.
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468206
08HumanRandomized controlled trialSafety outcome
In adults with overweight or obesity, 4.3% of semaglutide-treated participants permanently discontinued treatment because of gastrointestinal adverse events.
In plain wordsIn adults with overweight or obesity, few people on semaglutide stopped treatment for stomach and gut side effects.
Peptide
Semaglutide
Outcome
Not applicablePermanent discontinuation for GI adverse events
Study
n = 2,117
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Discontinuation for GI AEs
4.3%
semaglutide 2.4 mg
Source sentences
Summary
Few semaglutide-treated participants (4.3%) permanently discontinued treatment for GI AEs.
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468207
09HumanRandomized controlled trialEfficacy outcome
In adults with overweight or obesity on semaglutide 2.4 mg, mean weight loss was similar in participants with and without gastrointestinal adverse events.
In plain wordsIn adults on semaglutide 2.4 mg, weight loss was similar whether or not they had gut side effects.
Peptide
Semaglutide
Outcome
No significant changeWeight loss by presence or absence of GI adverse events
Study
n = 2,117
Comparator
Participants without GI adverse events
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · 68 weeksAs given in this study (human).
Measurements
Mean weight loss without GI AEs
9.6 to 17.1%
STEP 1-3
Mean weight loss with GI AEs
11.4 to 17.7%
STEP 1-3
Source sentences
Summary
In STEP 1-3, mean WL with semaglutide 2.4 mg was similar in participants without (9.6%-17.1%) versus with GI AEs (11.4%-17.7%).
1 context sentence(design, population, supporting numbers)
Summary · context
AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262).
Report a problemFND-3451468208
10HumanRandomized controlled trialSafety outcome
In 803 adults who tolerated a 20-week semaglutide run-in, continued semaglutide 2.4 mg maintenance was well tolerated.
In plain wordsIn adults who tolerated the first 20 weeks of semaglutide, continuing 2.4 mg was well tolerated.
Peptide
Semaglutide
Outcome
Not applicableGI tolerability of maintenance in STEP 4
Study
n = 803
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · 20 weeks run-in, then maintenanceAs given in this study (human).
Source sentences
Summary
In STEP 4, semaglutide 2.4 mg maintenance was well tolerated.
1 context sentence(design, population, supporting numbers)
Summary · context
GI tolerability with semaglutide 2.4 mg maintenance and cessation after dose escalation was evaluated using STEP 4 data among 803 participants tolerating 20 weeks of semaglutide run-in.
Report a problemFND-3451468210

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 2Current
11 Oct 2026, 00:50 UTC
Study results updated
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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Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss.

Summary

Results from this study10

Version history

Subjects

Publication types

MeSH terms

Keywords