Persistence-Dependent Effectiveness of Tirzepatide on the Cardio-Metabolic-Kidney Syndrome Outcomes in Obesity: Real-World Evidence from the United Arab Emirates.

INTRODUCTION: Tirzepatide has been associated with significant reductions in body weight in randomized clinical trials. However, real-world evidence evaluating the multisystemic effects of tirzepatide across the cardio-metabolic-kidney (CKM) continuum remains limited. The aim of this study was to assess the real-world persistence-driven cumulative benefits of tirzepatide beyond weight reduction in adults with obesity but without type 2 diabetes mellitus (T2DM). METHODS: This single-center observational cohort study evaluated in the United Arab Emirates adults with obesity (body mass index [BMI] ≥ 30 kg/m) treated with tirzepatide. Participants were stratified by treatment persistence: ≤ 1 year (short-term) and > 1 year (long-term). Anthropometric, glycemic, lipid, hepatic, and renal outcomes were assessed at baseline and follow-up. RESULTS: One hundred participants (25 women; mean age 37.6 ± 10.0 years; baseline BMI 35.0 [33.0-39.0] kg/m) were included. Median weight reduction was - 8.1% in the short-term group and - 22.6% in the long-term group (p < 0.001). 62% of long-term treated individuals achieved > 15% weight loss versus 20% among short-term users. Significant between-group differences were observed in BMI (- 8.3% vs. - 19.1%), waist circumference (- 4.0% vs. - 9.2%), and glycated hemoglobin (HbA1c) (- 5.0% vs. - 7.2%). Total cholesterol decreased by - 10.1% vs. - 18.7% (p = 0.005), low-density lipoprotein cholesterol (LDL-C) by - 9.6% vs. - 30.5% (p < 0.001), and triglycerides by - 11.2% vs. - 32.5% (p < 0.001). Liver enzymes, aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) declined by - 11.3% and - 13.2%, respectively, in long term group with no significant improvement in short term group (between-groups p values for both liver enzymes < 0.05). Serum creatinine declined significantly in the long-term group (- 6.6%, p < 0.001), estimated glomerular filtration rate (eGFR) increasing by + 3.2% (p = 0.001), and blood urea nitrogen (BUN) decreasing by - 7.8% (p = 0.006) while microalbuminuria showed no meaningful changes. Weight loss correlated with improvements in LDL-C, triglycerides, and SGOT, and inversely with high-density lipoprotein cholesterol (HDL-C) changes. CONCLUSIONS: Tirzepatide showed greater cumulative benefits across CKM syndrome outcomes during the second treatment year, highlighting the need to overcome adherence barriers in real-world settings.