Tirzepatide as a therapeutic tool for kidney impairment in obesity: insights from a real-world study

Obesity is a major risk factor for chronic kidney disease (CKD), contributing to kidney dysfunction through metabolic alterations and chronic inflammation. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown significant efficacy in weight loss and metabolic control, yet real-world data on its impact on kidney function are lacking. This study aimed to evaluate the impact of three months of tirzepatide treatment on kidney function and to identify the clinical predictors of changes in estimated glomerular filtration rate (eGFR) in adults with obesity in a real-world outpatient setting.

In this retrospective real-world study, 36 adults with overweight (BMI ≥ 27.0 kg/m²) with at least one weight-related comorbidity and patients with obesity (BMI ≥ 30.0 kg/m²) undergoing treatment with tirzepatide were included. Participants received weekly tirzepatide (2.5-5 mg) for three months. Anthropometric measurements, metabolic markers (fasting glucose, insulin, HOMA-IR, and HbA1c), inflammatory status (hs-CRP), and kidney parameters (serum creatinine and eGFR via CKD-EPI) were assessed at baseline and after 3 months of treatment.

After 3 months, serum creatinine decreased significantly (p < 0.001), and accordingly, eGFR increased after treatment (p < 0.001). In addition, significant reductions were observed in body weight (p < 0.001), BMI (p < 0.001), and waist circumference (p < 0.001). A significant decrease was observed in fasting plasma glucose (p < 0.001), HbA1c (p = 0.002), and insulin (p < 0.001) and, accordingly, in HOMA-IR (p < 0.001). Inflammatory status also improved significantly, with hs-CRP levels decreasing from baseline after 3 months of treatment with tirzepatide (p < 0.001). Correlation analysis demonstrated that ΔeGFR was inversely associated with Δweight loss (p = 0.008), ΔBMI (p = 0.007), and Δ fasting insulin (p = 0.011), while it showed a positive correlation with fasting plasma glucose (p < 0.001); a borderline negative association was also observed with ΔHOMA-IR (p = 0.053). Multiple regression analysis identified ΔBMI as the main independent predictor of ΔeGFR (p = 0.007), explaining 19.4% of the variance.

In a real-world setting, tirzepatide treatment was associated with improvements in kidney function alongside marked weight loss and metabolic improvements in individuals with obesity. The main driver of improvement in eGFR was primarily weight loss along with the improvement of insulin resistance, thus suggesting tirzepatide as a tool for the treatment of obesity-related kidney dysfunction.