The gynecologic tumor risk related to GLP-1 receptor agonists and SGLT2 inhibitors use: a network meta-analysis of 91 randomized controlled trials.

Tseng PT, Zeng BY, Hsu CW, Sun CK, Suen MW, Carvalho AF, Stubbs B, Chen YW, Chen TY, Lei WT, Chen PH, Chen JJ and 4 more

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Shiue YL, Zeng BS, Su KP, Liang CS

Journal of hematology & oncology27 Nov 2025Cited by 6 (Europe PMC)

PMID41310711PMCIDPMC12661836DOI10.1186/s13045-025-01750-xPepBankPUB-41310711

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Summary

BackgroundConcerns have emerged regarding the oncogenic potential of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors, particularly in relation to gynecologic malignancies. To date, no consensus has been reached on regimen-specific risks. This network meta-analysis (NMA) evaluated and compared the incidence of gynecologic tumors associated with various GLP-1 receptor agonists and SGLT2 inhibitors.MethodsFollowing a Cochrane-recommended confirmatory approach, we conducted a frequentist-based NMA using data from randomized controlled trials (RCTs) including female participants. Systematic searches of major databases were conducted through March 3, 2025. The primary outcome was the incidence of gynecologic tumors; drop-out rates served as an acceptability endpoint. Bayesian sensitivity analyses were conducted for validation.ResultsThis NMA included 91 RCTs comprising 224,986 participants (89,558 females). Only high-dose tirzepatide (15mg/week) was associated with significantly increased overall gynecologic tumor risk compared to controls [odds ratio (OR) = 2.37, 95% confidence interval (CI): 1.04-5.39; absolute risk difference= 0.57%; number needed to harm = 176]. Site-specific analysis noticed that both high-dose tirzepatide (15mg/week) (OR = 4.65, 95% CI: 1.28-16.94) and low-dose tirzepatide (5mg/week) (OR = 4.61, 95% CI: 1.07-19.90) were associated with a significantly elevated risk of intra-uterus tumor. No other regimen demonstrated a significant elevation in risk.ConclusionsTirzepatide appears to be associated with gynecologic tumor risk, particularly intra-uterus neoplasms. Given that these agents are frequently prescribed to individuals with predisposing risk factors, personalized risk-benefit evaluation is warranted. However, more data are needed to confirm whether this association is causal and not due to chance/bias or not. Besides, longitudinal research is essential to elucidate underlying mechanisms and guide clinical decision-making.Trial registrationPROSPERO CRD420251003016: The study protocol was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB E202516007).

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

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

01HumanSystematic reviewSafety outcome
In a network meta-analysis of randomized trials, tirzepatide 15 mg/week was associated with a significantly increased overall gynecologic tumor risk versus controls.
In plain wordsIn a pooled analysis of trials, tirzepatide 15 mg a week was linked to more gynecologic tumors than control treatment.
Peptide
Tirzepatide
Outcome
IncreaseOverall gynecologic tumor risk, 15 mg/week
Study
n: not reported in source
Comparator
Controls
Outcome group
Cancer risk · Cancer
Studied dose
15 mg/weekAs given in this study (human).
Measurements
Odds ratio
2.37 ratio
overall gynecologic tumor, 15 mg/week
Absolute risk difference
0.57%
15 mg/week
Number needed to harm
176 patients
15 mg/week
Source sentences
Summary
Only high-dose tirzepatide (15mg/week) was associated with significantly increased overall gynecologic tumor risk compared to controls [odds ratio (OR) = 2.37, 95% confidence interval (CI): 1.04-5.39; absolute risk difference= 0.57%; number needed to harm = 176].
1 context sentence(design, population, supporting numbers)
Summary · context
This NMA included 91 RCTs comprising 224,986 participants (89,558 females).
Show in the study text Report a problemFND-4131071101
02HumanSystematic reviewSafety outcome
In a network meta-analysis of randomized trials, tirzepatide 15 mg/week was associated with a significantly elevated risk of intra-uterus tumor versus controls.
In plain wordsIn a pooled analysis of trials, tirzepatide 15 mg a week was linked to more tumors of the uterus than control treatment.
Peptide
Tirzepatide
Outcome
IncreaseIntra-uterus tumor risk, 15 mg/week
Study
n: not reported in source
Comparator
Controls
Outcome group
Cancer risk · Cancer
Studied dose
15 mg/weekAs given in this study (human).
Measurements
Odds ratio
4.65 ratio
intra-uterus tumor, 15 mg/week
Source sentences
Summary
Site-specific analysis noticed that both high-dose tirzepatide (15mg/week) (OR = 4.65, 95% CI: 1.28-16.94) and low-dose tirzepatide (5mg/week) (OR = 4.61, 95% CI: 1.07-19.90) were associated with a significantly elevated risk of intra-uterus tumor.
1 context sentence(design, population, supporting numbers)
Summary · context
This NMA included 91 RCTs comprising 224,986 participants (89,558 females).
Show in the study text Report a problemFND-4131071102
03HumanSystematic reviewSafety outcome
In a network meta-analysis of randomized trials, tirzepatide 5 mg/week was associated with a significantly elevated risk of intra-uterus tumor versus controls.
In plain wordsIn a pooled analysis of trials, tirzepatide 5 mg a week was linked to more tumors of the uterus than control treatment.
Peptide
Tirzepatide
Outcome
IncreaseIntra-uterus tumor risk, 5 mg/week
Study
n: not reported in source
Comparator
Controls
Outcome group
Cancer risk · Cancer
Studied dose
5 mg/weekAs given in this study (human).
Measurements
Odds ratio
4.61 ratio
intra-uterus tumor, 5 mg/week
Source sentences
Summary
Site-specific analysis noticed that both high-dose tirzepatide (15mg/week) (OR = 4.65, 95% CI: 1.28-16.94) and low-dose tirzepatide (5mg/week) (OR = 4.61, 95% CI: 1.07-19.90) were associated with a significantly elevated risk of intra-uterus tumor.
1 context sentence(design, population, supporting numbers)
Summary · context
This NMA included 91 RCTs comprising 224,986 participants (89,558 females).
Show in the study text Report a problemFND-4131071103

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Version 2Current
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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