Overweight (OW) and obesity (OB) affect nearly two thirds of adults with type 1 diabetes (T1D), contributing to suboptimal glucose control, cardiovascular disease (CVD), and diabetic kidney disease (DKD). Many newer drugs such as tirzepatide (a dual-incretin) and sodium-glucose cotransporter-2 inhibitors are approved for people with type 2 diabetes associated with CVD and DKD. We evaluated CVD and DKD biomarkers with off-label long-term (21 months) use of tirzepatide in OW/OB adults with T1D.In this retrospective chart review study, we analyzed data for 84 OW/OB adults with T1D who were prescribed tirzepatide since July 2022 and had used tirzepatide for at least 6 months. Controls (= 38) were frequency matched for age, diabetes duration, sex, glycosylated hemoglobin (HbA1c), and body mass index (BMI). Data were collected from electronic medical records before initiating tirzepatide and over 21 months of treatment. Linear mixed effects models were used to examine the changes in lipids, blood pressure, and estimated glomerular filtration rate (eGFR) over time in tirzepatide-treated adults versus controls.Baseline characteristics were similar except that tirzepatide users had a slightly higher baseline BMI than controls; 35.2 ± 4.8 kg/mand 33.3 ± 4.2 kg/m(= 0.03), respectively. Patients using tirzepatide lost significantly more weight (-59 ± 4.6 lbs [-23.4%]) compared with a gain of (+1.7 ± 5.0 lbs [+1.8%]) in controls over 21 months. The HbA1c decreased more in patients using tirzepatide than controls (-0.50 ± 0.07% and -0.24 ± 0.09%, respectively,= 0.017). Patients using tirzepatide significantly improved total and low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and eGFR; these changes remained significant even after adjusting for weight and HbA1c. The eGFR declined significantly in controls but not in the tirzepatide users.We conclude that long-term use of tirzepatide in OW/OB adults with T1D results in more than 23% weight loss and sustained improvement in glucose control. Irrespective of changes in weight and/or HbA1c, we observed significant improvement in cardiovascular biomarkers and preservation of kidney function. We strongly recommend a long-term randomized control trial with tirzepatide in patients with T1D.