Tirzepatide Shows No Increased Heart Failure Risk in Meta-Analysis
A review and meta-analysis published in Diabetes Metabolism Research and Reviews has revealed that tirzepatide has a neutral effect on heart failure outcomes in people with type 2 diabetes or obesity. Across 11 randomized controlled trials involving 13,378 participants, tirzepatide showed no significant difference in heart failure risk compared with placebo or other glucose-lowering medications. Yi-Meng He and colleagues conducted the study.
This study's background indicates that, at the time, evidence for the cardioprotective effect of tirzepatide was inconsistent; thus, further investigation was necessary to determine whether this dual GIP/GLP-1 receptor agonist would affect heart failure outcomes. The investigators also included the conclusions in the introduction to note that tirzepatide use is safe regarding T2DM and obesity management, without causing increased risk of heart failure.
The investigators performed a comprehensive systematic search in PubMed, Embase, The Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov from inception to February 13, 2025. Predefined tirzepatide- and heart failure-related keywords were used to screen the studies. Only RCTs were eligible. A total of 11 trials, all funded by Eli Lilly and Company, were included, representing 13,378 participants. Summary estimates of effects were calculated using RR with 95% CI. Additional statistical methods included subgroup analyses, heterogeneity testing using I² statistics, and evidence rating using the GRADE framework.
Results
The meta-analysis showed that tirzepatide had a neutral overall effect on outcomes in heart failure.
The pooled effect estimate was RR 0.63 (95% CI 0.35–1.13).
This effect was not statistically significant, as shown by p = 0.628 and I² = 0.0%, indicating no heterogeneity.
Clinically, the effect was also considered negligible because the absolute risk reduction was 0.17% and the NNT was 588, very far from the MID threshold established by the FDA of 1.5%.
Subgroup analyses disclosed meaningful differences: in participants ≤58 years, the risk ratio was 0.40 (95% CI 0.17–0.96), representing a 60% relative risk reduction, while participants >58 years had an RR of 0.86 (95% CI 0.39–1.90).
When further comparing tirzepatide monotherapy versus combination therapy, monotherapy had an RR of 0.43 (95% CI 0.20–0.88), reflecting a 57% relative risk reduction, whereas combination therapy had an RR of 2.25 (95% CI 0.51–9.87).
The remainder of the subgroup analyses-stratified by body weight, BMI, FPG, HbA1c levels, dosing, or intervention duration-showed no association between tirzepatide and heart failure risk.
This systematic review with meta-analysis indicates no overall effect of tirzepatide on heart failure outcomes among patients with T2DM or obesity. Overall findings support tirzepatide as a safe therapeutic approach for metabolic disease management without increasing the risk of heart failure.
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