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

Abstract

Background/aims: Tirzepatide has been approved for weight loss in adults with obesity. However, real-world data are still needed. This real-world prospective study is among the first to evaluate the short-term metabolic effects of low-dose tirzepatide in adults with obesity but without diabetes mellitus (DM). Secondary endpoints included associations between these changes and anthropometric or baseline metabolic parameters.

Methods: In this prospective observational study, adults with obesity but without diabetes mellitus received tirzepatide (2.5 mg/week, escalating to 5 mg/week, subcutaneously) for 12 weeks. Body weight, body mass index (BMI), total (TC), low-density (LDL-C) and high-density lipoprotein cholesterol (HDL-C), triglycerides, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and hepatic steatosis index (HSI) were measured at baseline and week 12.

Results: Seventy-five participants (mean age 46.9 ± 9.9 years) were included. After 12 weeks, body weight (-8.1 ± 4.3 %) and BMI significantly decreased. TC, LDL-C, triglycerides, FPG, HbA1c, and HSI were significantly reduced and inversely associated with their baseline levels. HbA1c and HSI changes correlated with weight loss. No effect was observed on HDL-C. Statin use had no impact on outcomes.

Conclusion: Short-term low-dose tirzepatide improves the lipid profile, HbA1c, and HSI in obese adults without DM, especially in those with abnormal baseline values. Lipid changes occurred independently of weight loss.

Keywords: Cardiometabolic risk; Estimated glomerular filtration rate; Hemoglobin A1c; Hepatic steatosis; Lipid profile; Obesity; Statin therapy; Tirzepatide.