Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Kommu S, Sharma PP, Gabor RM

Obesity reviews : an official journal of the International Association for the Study of Obesity13 Jun 2025Cited by 6 (Europe PMC)

PMID40510020PMCIDPMC12531717DOI10.1111/obr.13961PepBankPUB-40510020

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Summary

Tirzepatide has positive effects on weight loss in individuals with overweight or obesity. Considering its broad side-effect profile, its efficacy and safety in individuals without diabetes mellitus (DM) are yet to be fully understood. To address this, we conducted a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM, which showed that tirzepatide, when compared with placebo, resulted in a change in percentage body weight with a mean difference (MD) of -16.32% (95% CI: -18.35 to -14.29) and change in absolute body weight in kilograms (MD -13.95 kg; -18.83 to -9.07). There were significant reductions in body mass index and waist circumference when compared with placebo, with MDs of -5.89 kg/m² (-8.97 to -2.81) and -12.31 cm (-13.93 to -10.68), respectively. It was associated with gastrointestinal (GI) side effects: nausea (relative risk [RR] 3.11; 2.74-3.54), vomiting (RR 5.94; 4.50-7.85), diarrhea (RR 2.92; 2.53-3.37), and constipation (RR 2.85; 2.38-3.42). Serious adverse events were not statistically significant (RR 0.93; 0.76-1.13), but serious GI events and discontinuation due to adverse events were significant (RRs 3.07; 2.03-4.66, and 2.29; 1.74-3.01, respectively). In conclusion, this meta-analysis suggests that in patients with overweight or obesity without DM, tirzepatide is effective for significant weight loss. Though the overall risk of serious adverse events is not higher compared with placebo, it carries an elevated risk of GI side effects, serious GI events, and discontinuation due to adverse effects.

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

Results from this study11

11 results from studies that gave the peptide. 11 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, tirzepatide reduced percentage body weight more than placebo.
In plain wordsIn adults with overweight or obesity without diabetes, tirzepatide led to more weight loss than placebo.
Peptide
Tirzepatide
Outcome
DecreasePercentage body weight change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
mean difference
−16.32%
percentage body weight
Source sentences
Summary
tirzepatide, when compared with placebo, resulted in a change in percentage body weight with a mean difference (MD) of -16.32% (95% CI: -18.35 to -14.29)
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002001
02HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, tirzepatide reduced absolute body weight more than placebo.
In plain wordsIn adults with overweight or obesity without diabetes, tirzepatide reduced body weight in kilograms more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseAbsolute body weight change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
mean difference
−13.95 kg
absolute body weight
Source sentences
Summary
change in absolute body weight in kilograms (MD -13.95 kg; -18.83 to -9.07)
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002002
03HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, tirzepatide reduced body mass index more than placebo.
In plain wordsIn adults with overweight or obesity without diabetes, tirzepatide lowered body mass index more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseBody mass index change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
mean difference
−5.89 kg/m2
body mass index
Source sentences
Summary
There were significant reductions in body mass index and waist circumference when compared with placebo, with MDs of -5.89 kg/m² (-8.97 to -2.81) and -12.31 cm (-13.93 to -10.68), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002003
04HumanSystematic reviewEfficacy outcome
In adults with overweight or obesity without diabetes, tirzepatide reduced waist circumference more than placebo.
In plain wordsIn adults with overweight or obesity without diabetes, tirzepatide reduced waist size more than placebo.
Peptide
Tirzepatide
Outcome
DecreaseWaist circumference change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Measurements
mean difference
−12.31 cm
waist circumference
Source sentences
Summary
There were significant reductions in body mass index and waist circumference when compared with placebo, with MDs of -5.89 kg/m² (-8.97 to -2.81) and -12.31 cm (-13.93 to -10.68), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002004
05HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, tirzepatide increased the risk of nausea versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, nausea was more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseNausea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
relative risk
3.11 RR
nausea
Source sentences
Summary
It was associated with gastrointestinal (GI) side effects: nausea (relative risk [RR] 3.11; 2.74-3.54), vomiting (RR 5.94; 4.50-7.85), diarrhea (RR 2.92; 2.53-3.37), and constipation (RR 2.85; 2.38-3.42).
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002005
06HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, tirzepatide increased the risk of vomiting versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, vomiting was more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseVomiting
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
relative risk
5.94 RR
vomiting
Source sentences
Summary
It was associated with gastrointestinal (GI) side effects: nausea (relative risk [RR] 3.11; 2.74-3.54), vomiting (RR 5.94; 4.50-7.85), diarrhea (RR 2.92; 2.53-3.37), and constipation (RR 2.85; 2.38-3.42).
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002006
07HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, tirzepatide increased the risk of diarrhea versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, diarrhea was more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseDiarrhea
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
relative risk
2.92 RR
diarrhea
Source sentences
Summary
It was associated with gastrointestinal (GI) side effects: nausea (relative risk [RR] 3.11; 2.74-3.54), vomiting (RR 5.94; 4.50-7.85), diarrhea (RR 2.92; 2.53-3.37), and constipation (RR 2.85; 2.38-3.42).
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002007
08HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, tirzepatide increased the risk of constipation versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, constipation was more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseConstipation
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
relative risk
2.85 RR
constipation
Source sentences
Summary
It was associated with gastrointestinal (GI) side effects: nausea (relative risk [RR] 3.11; 2.74-3.54), vomiting (RR 5.94; 4.50-7.85), diarrhea (RR 2.92; 2.53-3.37), and constipation (RR 2.85; 2.38-3.42).
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002008
09HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, serious adverse events did not differ significantly between tirzepatide and placebo.
In plain wordsIn adults with overweight or obesity without diabetes, serious adverse events were not clearly different between tirzepatide and placebo.
Peptide
Tirzepatide
Outcome
No significant changeSerious adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Measurements
relative risk
0.93 RR
serious adverse events
Source sentences
Summary
Serious adverse events were not statistically significant (RR 0.93; 0.76-1.13)
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002009
10HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, tirzepatide increased the risk of serious gastrointestinal events versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, serious stomach and gut events were more common with tirzepatide than with placebo.
Peptide
Tirzepatide
Outcome
IncreaseSerious gastrointestinal events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Measurements
relative risk
3.07 RR
serious gastrointestinal events
Source sentences
Summary
but serious GI events and discontinuation due to adverse events were significant (RRs 3.07; 2.03-4.66, and 2.29; 1.74-3.01, respectively).
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002010
11HumanSystematic reviewSafety outcome
In adults with overweight or obesity without diabetes, tirzepatide increased the risk of discontinuation due to adverse events versus placebo.
In plain wordsIn adults with overweight or obesity without diabetes, more people stopped tirzepatide because of side effects than stopped placebo.
Peptide
Tirzepatide
Outcome
IncreaseDiscontinuation due to adverse events
Study
n: not reported in source
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated
Measurements
relative risk
2.29 RR
discontinuation due to adverse events
Source sentences
Summary
but serious GI events and discontinuation due to adverse events were significant (RRs 3.07; 2.03-4.66, and 2.29; 1.74-3.01, respectively).
1 context sentence(design, population, supporting numbers)
Summary · context
a comprehensive meta-analysis of six randomized trials on individuals with overweight or obesity, without DM
Show in the study text Report a problemFND-4051002011

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

Version history

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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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