Obesity is a growing public health concern, closely linked to metabolic and cardiovascular complications. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has shown substantial weight loss effects in clinical trials; however, real-world data, especially at lower doses, remain limited. This study aimed to evaluate the short-term effects of tirzepatide 2.5 mg and 5.0 mg on weight, metabolic parameters, and tolerability in adults with obesity in a real-world outpatient setting. This retrospective multicenter study included 70 adults with obesity but without type 2 diabetes, treated with tirzepatide between January and June 2025 in the Campania Region, Italy. Anthropometric and biochemical parameters were assessed at baseline. Follow-up data were collected at dose transitions: from 2.5 mg to 5.0 mg, and from 5.0 mg to 7.5 mg, allowing assessment of the effects of the 2.5 mg and 5.0 mg doses. Seventy participants were included (mean age 50.7 ± 10.2 years; 60 % female; BMI 37.5 ± 6.8 kg/m2). Treatment led to dose-dependent reductions in body weight, BMI, and waist circumference (p < 0.001 for all vs baseline and between doses). Significant improvements were observed in total cholesterol (p = 0.006 between doses), LDL cholesterol (p = 0.001), triglycerides (p < 0.001), prediabetes prevalence (p < 0.001 vs baseline; p = 0.002 between doses), fasting plasma glucose (p < 0.001 vs baseline; p < 0.001 between doses), insulin (p < 0.001 vs baseline; p < 0.001 between doses), HoMA-IR (p < 0.001 vs baseline; p < 0.001 between doses), AST (p = 0.012 vs baseline; p = 0.006 between doses), and ALT (p < 0.001 vs baseline; p = 0.007 between doses). Amylase increased significantly only at 5.0 mg (p = 0.016), while lipase remained unchanged. Renal function (eGFR) improved at both doses (p = 0.025 for 2.5 mg; p = 0.005 for 5.0 mg). Gastrointestinal adverse events were mild and similar between doses. In this real-world cohort, tirzepatide at 2.5 mg and 5.0 mg led to substantial improvements in weight and metabolic health, with good tolerability. These findings support its use in routine obesity care and justify further longitudinal research. See also the graphical abstract(Fig. 1).
