Efficacy and safety of tirzepatide versus placebo in overweight or obese adults without diabetes: a systematic review and meta-analysis of randomized controlled trials.

Liu L, Shi H, Xie M, Sun Y, Nahata MC

International journal of clinical pharmacy22 Jul 2024Cited by 19 (Europe PMC)

PMID39037553PMCIDPMC11576767DOI10.1007/s11096-024-01779-xPepBankPUB-39037553

Summary

BackgroundTirzepatide was approved to treat type 2 diabetes and obesity, but its efficacy and safety in patients without diabetes has not been investigated.AimThis meta-analysis aimed to evaluate the efficacy and safety of tirzepatide compared to placebo in overweight or obese patients without diabetes.MethodPubMed, Embase and Cochrane were searched on January 18, 2024. Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included. Efficacy outcomes included the proportion of participants achieving weight loss targets, changes in body weight (%), body mass index (BMI), waist circumference (WC), and blood pressure (BP). Safety outcomes were commonly reported adverse events. Standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CIs) were used for continuous and dichotomous outcomes, respectively.ResultsThree RCTs with 3901 participants were included. Tirzepatide was associated with increased proportion of participants achieving weight loss targets, reduced body weight (SMD - 1.61, 95% CI - 2.20 to - 1.02), BMI (SMD - 2.13, 95% CI - 3.08 to - 1.18), WC (SMD - 0.91, 95% CI - 1.14 to - 0.69), and BP versus placebo. However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo.ConclusionTirzepatide significantly reduced weight and improved metabolic markers among overweight or obese without diabetes. However, increased adverse events highlights the need for benefits versus risks assessment before initiation and continuous monitoring.

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

Results from this study8

8 results from studies that gave the peptide. 8 results from people.

01HumanSystematic reviewEfficacy outcome
In overweight or obese adults without diabetes, tirzepatide increased the proportion reaching weight loss targets versus placebo.
In plain wordsIn overweight or obese adults without diabetes, more people reached their weight loss targets on tirzepatide than on placebo.
Peptide
Tirzepatide
Outcome
IncreaseProportion achieving weight loss targets
Study
n = 3,901
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Tirzepatide was associated with increased proportion of participants achieving weight loss targets
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755301
02HumanSystematic reviewEfficacy outcome
In overweight or obese adults without diabetes, tirzepatide reduced body weight versus placebo.
In plain wordsIn overweight or obese adults without diabetes, tirzepatide led to more weight loss than placebo.
Peptide
Tirzepatide
Outcome
DecreaseBody weight
Study
n = 3,901
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
SMD
−1.61 SMD
body weight
Source sentences
Summary
reduced body weight (SMD - 1.61, 95% CI - 2.20 to - 1.02)
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755302
03HumanSystematic reviewEfficacy outcome
In overweight or obese adults without diabetes, tirzepatide reduced BMI versus placebo.
In plain wordsIn overweight or obese adults without diabetes, tirzepatide lowered BMI more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseBody mass index
Study
n = 3,901
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
SMD
−2.13 SMD
BMI
Source sentences
Summary
BMI (SMD - 2.13, 95% CI - 3.08 to - 1.18)
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755303
04HumanSystematic reviewEfficacy outcome
In overweight or obese adults without diabetes, tirzepatide reduced waist circumference versus placebo.
In plain wordsIn overweight or obese adults without diabetes, tirzepatide reduced waist size more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseWaist circumference
Study
n = 3,901
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
SMD
−0.91 SMD
waist circumference
Source sentences
Summary
WC (SMD - 0.91, 95% CI - 1.14 to - 0.69)
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755304
05HumanSystematic reviewEfficacy outcome
In overweight or obese adults without diabetes, tirzepatide reduced blood pressure versus placebo.
In plain wordsIn overweight or obese adults without diabetes, tirzepatide lowered blood pressure more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseBlood pressure
Study
n = 3,901
Comparator
Placebo
Outcome group
Blood pressure · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
and BP versus placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755305
06HumanSystematic reviewSafety outcome
In overweight or obese adults without diabetes, nausea risk was significantly higher with tirzepatide than with placebo.
In plain wordsIn overweight or obese adults without diabetes, nausea was more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseNausea
Study
n = 3,901
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
OR
4.26 ratio
nausea
Source sentences
Summary
However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81)
2 context sentences(design, population, supporting numbers)
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755306
07HumanSystematic reviewSafety outcome
In overweight or obese adults without diabetes, vomiting risk was significantly higher with tirzepatide than with placebo.
In plain wordsIn overweight or obese adults without diabetes, vomiting was more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseVomiting
Study
n = 3,901
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
OR
8.35 ratio
vomiting
Source sentences
Summary
vomiting (OR 8.35, 95% CI 5.19 to 13.45)
3 context sentences(design, population, supporting numbers)
Summary · context
was significantly higher for tirzepatide versus placebo.
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755307
08HumanSystematic reviewSafety outcome
In overweight or obese adults without diabetes, diarrhea risk was significantly higher with tirzepatide than with placebo.
In plain wordsIn overweight or obese adults without diabetes, diarrhea was more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseDiarrhea
Study
n = 3,901
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
OR
3.57 ratio
diarrhea
Source sentences
Summary
diarrhea (OR 3.57, 95% CI 2.80 to 4.57)
3 context sentences(design, population, supporting numbers)
Summary · context
was significantly higher for tirzepatide versus placebo.
Summary · context
Randomized controlled trials (RCTs) that used tirzepatide in overweight or obese adults without diabetes were included.
Summary · context
Three RCTs with 3901 participants were included.
Show in the study text Report a problemFND-3903755308

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
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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