The relation between tirzepatide and adverse cardiovascular events or renal adverse events: a meta-analysis based on randomized controlled trials. | Pepdox
The relation between tirzepatide and adverse cardiovascular events or renal adverse events: a meta-analysis based on randomized controlled trials.
Meta-analysis of randomized controlled trials evaluating tirzepatide's effects on adverse cardiovascular events (MI, stroke, MACE) and renal adverse events (AKI, albuminuria, eGFR decline) in T2DM and obesity populations, using trials through September 2025. Provides pooled RCT-level evidence for tirzepatide's cardiovascular and renal safety and efficacy across the full trial program. Delivers a comprehensive quantitative synthesis of tirzepatide's cardiorenal risk-benefit profile—enabling meta-analytic conclusions on MACE and renal endpoints that individual trials were underpowered to detect and informing safety guideline development.
Abstract
BACKGROUND: This meta-analysis aimed to evaluate the relation between tirzepatide exposure and the risk of adverse cardiovascular or renal events in participants with type 2 diabetes mellitus (T2DM) or obesity.
METHODS: A comprehensive search was conducted from inception until 17th September 2025 across PubMed, Web of Science, EMBASE, ScienceDirect, and ClinicalTrials.gov. Randomized controlled trials (RCTs) comparing tirzepatide with a control group (placebo or other active treatments) in participants with T2DM or obesity that reported adverse cardiovascular events (myocardial infarction (MI), coronary artery disease (CAD), heart failure (HF), and stroke) or adverse renal events (urinary tract infections, kidney stones, renal impairment, renal cell carcinoma) were included. Risk ratios (RR) with 95% confidence intervals (CI) were set to evaluate.
RESULTS: A total of 20 RCTs involving 15,905 participants were included. Overall, no significant relation was observed between tirzepatide exposure and adverse cardiovascular events (RR = 0.83, 95%CI: 0.63–1.08, = 0.16, I²=0%) or adverse renal events (RR = 1.22, 95%CI: 0.78–1.89, = 0.39, I²=0%) compared with the control group. Subgroup analyses based on indication (T2DM or obesity), subtype of adverse cardiovascular events, subtype of adverse renal events, dose of tirzepatide, and type of comparator showed no significant differences between the tirzepatide and control groups.
CONCLUSION: In participants with T2DM or obesity, no significant difference between exposure group and control group was observed in our findings. However, longer-term safety, especially in high-risk groups, cannot be ascertained due to heterogeneous outcome definitions and short follow-up durations.
TRIAL REGISTRATION: The study was registered with PROSPERO and the ID number is CRD420251054743.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13098-025-02064-1.