Short-term effects of low-dose tirzepatide on lipid profile, glucose homeostasis and hepatic steatosis index in adults with obesity, but without diabetes mellitus: a prospective observational study.
Level 4 - case-series / case-control
Single-arm prospective observational study without a control group
PubMed 41075711 · doi:10.1016/j.jdiacomp.2025.109181
What was done
In a prospective observational study, 75 adults with obesity but without diabetes mellitus (mean age 46.9 ± 9.9 years) received low-dose subcutaneous tirzepatide (2.5 mg/week escalated to 5 mg/week) for 12 weeks. Body weight, BMI, total cholesterol (TC), LDL-C, HDL-C, triglycerides, fasting plasma glucose (FPG), HbA1c, and hepatic steatosis index (HSI) were measured at baseline and week 12. Associations between metabolic changes, weight loss, baseline parameters, and statin use were evaluated.
What was found
After 12 weeks, body weight decreased significantly by -8.1 ± 4.3%, with a concurrent decrease in BMI. Significant reductions were observed in TC, LDL-C, triglycerides, FPG, HbA1c, and HSI (absolute numerical changes not provided in the abstract), which were inversely associated with baseline levels. Changes in HbA1c and HSI correlated with weight loss, while lipid improvements occurred independently of weight loss. No effect was observed on HDL-C, and statin use did not alter outcomes.
Why it matters
This real-world study demonstrates that short-term, low-dose tirzepatide produces meaningful weight loss and metabolic improvements in individuals with obesity without diabetes, with lipid benefits occurring independently of weight loss.
Limits
The study is limited by an uncontrolled, single-arm design with no comparator or placebo group, a small sample size (n = 75), and a brief follow-up period of 12 weeks. Hepatic steatosis was assessed via a surrogate index rather than imaging or histology, and exact numerical values for laboratory endpoints were omitted from the abstract.
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