A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable?

Meng Z, Yang M, Wen H, Zhou S, Xiong C, Wang Y

Frontiers in endocrinology27 Mar 2023Cited by 25 (Europe PMC)

PMID37051199PMCIDPMC10084319DOI10.3389/fendo.2023.1121387PepBankPUB-37051199

Summary

AimsTirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). At present, there is no controversy over its effectiveness, but its safety. We conducted a systematic review to assess the safety of tirzepatide.MethodsWe searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias. The systematic review was conducted via Revman5.4.ResultsNine RCTs with a total of 9818 patients were included. The overall safety profile of tirzepatide is similar to GLP-1RAs, except for the hypoglycemia (tirzepatide 15mg, pooled RR=3.83, 95% CI [1.19- 12.30], P=0.02) and discontinuation (tirzepatide 10mg, pooled RR=1.75,95%CI[1.16-2.63], P=0.007 and 15mg, pooled RR=2.03, 95%CI [1.37-3.01], P=0.0004). It also showed that the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (P>0.05); Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (P), discontinuation (P) and injection-site reaction (P); The rates of vomiting and diarrhea were dose-dependence at the range of 5-15mg.ConclusionThe safety profile of tirzepatide is generally acceptable, similar to GLP-1 RAs. It is necessary to pay attention to its specific adverse events (hypoglycemia and discontinuation) at high doses (10mg or higher). Nausea, vomiting, diarrhea, discontinuation and injection-site reaction were dose-dependence among specific dose ranges.As the heterogeneity in different studies by interventions, the results may be with biases and the further confirmation is needed. Meanwhile, more well-designed trials are needed to control the confounding factors and ensure adequate sample size.

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

Results from this study13

13 results from studies that gave the peptide. 13 results from people.

01HumanSystematic reviewSafety outcome
In patients in randomized trials, the overall safety profile of tirzepatide was similar to that of GLP-1 receptor agonists, with exceptions for hypoglycemia and discontinuation.
In plain wordsIn patients in trials, tirzepatide had a safety profile similar to GLP-1 drugs, except for low blood sugar and stopping treatment.
Peptide
Tirzepatide
Outcome
No significant changeOverall safety profile versus GLP-1 RAs
Study
n = 9,818
Comparator
GLP-1 receptor agonists
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Source sentences
Summary
The overall safety profile of tirzepatide is similar to GLP-1RAs
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119901
02HumanSystematic reviewSafety outcome
In patients in randomized trials, hypoglycemia was more frequent with tirzepatide 15 mg than with GLP-1 receptor agonists (pooled RR 3.83).
In plain wordsIn patients in trials, low blood sugar was more frequent with tirzepatide 15 mg than with GLP-1 drugs.
Peptide
Tirzepatide
Outcome
IncreaseHypoglycemia, 15 mg
Study
n: not reported in source
Comparator
GLP-1 receptor agonists
Outcome group
Adverse events · Whole body
Studied dose
15 mgAs given in this study (human).
Measurements
Pooled RR
3.83
hypoglycemia, tirzepatide 15 mg
Source sentences
Summary
The overall safety profile of tirzepatide is similar to GLP-1RAs, except for the hypoglycemia (tirzepatide 15mg, pooled RR=3.83, 95% CI [1.19- 12.30], P=0.02)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119902
03HumanSystematic reviewSafety outcome
In patients in randomized trials, discontinuation was more frequent with tirzepatide 10 mg than with GLP-1 receptor agonists (pooled RR 1.75).
In plain wordsIn patients in trials, more people stopped treatment with tirzepatide 10 mg than with GLP-1 drugs.
Peptide
Tirzepatide
Outcome
IncreaseDiscontinuation, 10 mg
Study
n: not reported in source
Comparator
GLP-1 receptor agonists
Outcome group
Adverse events · Whole body
Studied dose
10 mgAs given in this study (human).
Measurements
Pooled RR
1.75
discontinuation, tirzepatide 10 mg
Source sentences
Summary
discontinuation (tirzepatide 10mg, pooled RR=1.75,95%CI[1.16-2.63], P=0.007
3 context sentences(design, population, supporting numbers)
Summary · context
The overall safety profile of tirzepatide is similar to GLP-1RAs
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119903
04HumanSystematic reviewSafety outcome
In patients in randomized trials, discontinuation was more frequent with tirzepatide 15 mg than with GLP-1 receptor agonists (pooled RR 2.03).
In plain wordsIn patients in trials, more people stopped treatment with tirzepatide 15 mg than with GLP-1 drugs.
Peptide
Tirzepatide
Outcome
IncreaseDiscontinuation, 15 mg
Study
n: not reported in source
Comparator
GLP-1 receptor agonists
Outcome group
Adverse events · Whole body
Studied dose
15 mgAs given in this study (human).
Measurements
Pooled RR
2.03
discontinuation, tirzepatide 15 mg
Source sentences
Summary
and 15mg, pooled RR=2.03, 95%CI [1.37-3.01], P=0.0004)
3 context sentences(design, population, supporting numbers)
Summary · context
The overall safety profile of tirzepatide is similar to GLP-1RAs
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119904
05HumanSystematic reviewSafety outcome
In patients in randomized trials, dose escalation of tirzepatide did not raise the rate of total adverse events (P>0.05).
In plain wordsIn patients in trials, raising the tirzepatide dose did not raise the rate of adverse events overall.
Peptide
Tirzepatide
Outcome
No significant changeTotal adverse events with dose escalation
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
5-15 mgAs given in this study (human).
Source sentences
Summary
the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (P>0.05)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119905
06HumanSystematic reviewSafety outcome
In patients in randomized trials, dose escalation of tirzepatide did not raise the rate of severe adverse events (P>0.05).
In plain wordsIn patients in trials, raising the tirzepatide dose did not raise the rate of severe adverse events.
Peptide
Tirzepatide
Outcome
No significant changeSevere adverse events with dose escalation
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
5-15 mgAs given in this study (human).
Source sentences
Summary
the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (P>0.05)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119906
07HumanSystematic reviewSafety outcome
In patients in randomized trials, dose escalation of tirzepatide did not raise the rate of gastrointestinal adverse events overall (P>0.05).
In plain wordsIn patients in trials, raising the tirzepatide dose did not raise the rate of stomach and gut side effects overall.
Peptide
Tirzepatide
Outcome
No significant changeGastrointestinal adverse events with dose escalation
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5-15 mgAs given in this study (human).
Source sentences
Summary
the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (P>0.05)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119907
08HumanSystematic reviewSafety outcome
In patients in randomized trials, dose escalation of tirzepatide did not raise the rate of hypoglycemia (P>0.05).
In plain wordsIn patients in trials, raising the tirzepatide dose did not raise the rate of low blood sugar.
Peptide
Tirzepatide
Outcome
No significant changeHypoglycemia with dose escalation
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
5-15 mgAs given in this study (human).
Source sentences
Summary
the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (P>0.05)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119908
09HumanSystematic reviewSafety outcome
In patients in randomized trials, nausea was more frequent with tirzepatide 10 mg and 15 mg than with 5 mg (P<0.001).
In plain wordsIn patients in trials, nausea was more frequent with tirzepatide 10 mg and 15 mg than with 5 mg.
Peptide
Tirzepatide
Outcome
IncreaseNausea, 10 mg and 15 mg versus 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
10 mg and 15 mgAs given in this study (human).
Source sentences
Summary
Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (P), discontinuation (P) and injection-site reaction (P)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119909
10HumanSystematic reviewSafety outcome
In patients in randomized trials, discontinuation was more frequent with tirzepatide 10 mg and 15 mg than with 5 mg (P<0.05).
In plain wordsIn patients in trials, more people stopped treatment with tirzepatide 10 mg and 15 mg than with 5 mg.
Peptide
Tirzepatide
Outcome
IncreaseDiscontinuation, 10 mg and 15 mg versus 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Adverse events · Whole body
Studied dose
10 mg and 15 mgAs given in this study (human).
Source sentences
Summary
Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (P), discontinuation (P) and injection-site reaction (P)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119910
11HumanSystematic reviewSafety outcome
In patients in randomized trials, injection-site reactions were more frequent with tirzepatide 10 mg and 15 mg than with 5 mg (P<0.01).
In plain wordsIn patients in trials, injection-site reactions were more frequent with tirzepatide 10 mg and 15 mg than with 5 mg.
Peptide
Tirzepatide
Outcome
IncreaseInjection-site reaction, 10 mg and 15 mg versus 5 mg
Study
n: not reported in source
Comparator
Tirzepatide 5 mg
Outcome group
Adverse events · Whole body
Studied dose
10 mg and 15 mgAs given in this study (human).
Source sentences
Summary
Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (P), discontinuation (P) and injection-site reaction (P)
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119911
12HumanSystematic reviewSafety outcome
In patients in randomized trials, the rate of vomiting with tirzepatide was dose-dependent across 5-15 mg.
In plain wordsIn patients in trials, vomiting with tirzepatide became more frequent as the dose rose from 5 mg to 15 mg.
Peptide
Tirzepatide
Outcome
IncreaseVomiting rate by dose
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5-15 mgAs given in this study (human).
Source sentences
Summary
The rates of vomiting and diarrhea were dose-dependence at the range of 5-15mg.
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119912
13HumanSystematic reviewSafety outcome
In patients in randomized trials, the rate of diarrhea with tirzepatide was dose-dependent across 5-15 mg.
In plain wordsIn patients in trials, diarrhea with tirzepatide became more frequent as the dose rose from 5 mg to 15 mg.
Peptide
Tirzepatide
Outcome
IncreaseDiarrhea rate by dose
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5-15 mgAs given in this study (human).
Source sentences
Summary
The rates of vomiting and diarrhea were dose-dependence at the range of 5-15mg.
2 context sentences(design, population, supporting numbers)
Summary · context
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias.
Summary · context
Nine RCTs with a total of 9818 patients were included.
Show in the study text Report a problemFND-3705119913

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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
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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