"Tirzepatide may lower LDL cholesterol and enhance lipid profiles, particularly at 15 mg and in those with metabolic risk, though study variability and short follow-ups limit firm conclusions," Isaac Hong from the Faculty of Medicine, University of Costa Rica, and colleagues wrote.
The researchers conducted a thorough literature search across PubMed, EMBASE, and Web of Science databases up to June 26, 2025. The analysis was conducted in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, ensuring methodological rigor. Eligible studies included both randomized controlled trials and observational studies involving adults aged 18 years and older, with reported LDL levels before and after tirzepatide treatment.
Key findings of the study were as follows:
- Higher doses of tirzepatide, especially the 15 mg dose, were associated with modest but meaningful reductions in LDL cholesterol levels.
- Some studies reported improvements in LDL particle size, enhancing overall lipid profile quality.
- There were greater reductions in LDL cholesterol in individuals younger than 65 years.
- The findings suggest possible age-related differences in response to tirzepatide treatment.
However, the findings varied across studies. Observational studies, in particular, were affected by limitations such as confounding variables and additional treatments received by participants, making it difficult to isolate the specific impact of tirzepatide on LDL levels. Moreover, the short duration of follow-up in many studies restricted the ability to assess long-term lipid outcomes.
The review also highlighted key limitations in the existing evidence. Differences in study design, measurement techniques, and frequent use of co-interventions made it challenging to draw uniform conclusions. There was also a lack of detailed data on LDL subfractions, which are increasingly recognized for their role in cardiovascular risk assessment.
Despite these challenges, the review suggests that tirzepatide may offer benefits beyond glucose control and weight management. Its mechanisms—such as enhancing insulin sensitivity, promoting weight loss, and modulating liver lipid metabolism—may contribute to improvements in LDL cholesterol, particularly in patients with underlying metabolic issues.
The authors emphasize the need for more robust clinical trials with standardized lipid assessments and longer follow-up periods. Such research would help clarify tirzepatide's role in managing dyslipidemia and its potential to reduce cardiovascular events.
They concluded, "While early findings are promising, the evidence on tirzepatide's effect on LDL cholesterol remains inconclusive. More high-quality research is essential to determine its place in cardiovascular risk reduction strategies."
Reference:
Hong I, Hidalgo Ramos R A, Dufner Krieger S, et al. (July 20, 2025) Effects of Tirzepatide on Low-Density Lipoprotein Cholesterol Levels in Adults: A Systematic Review. Cureus 17(7): e88390. doi:10.7759/cureus.88390
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