Efficacy and safety of tirzepatide in subjects with type 2 diabetes and chronic kidney disease: a prospective, two-arm observational study.

BACKGROUND: Tirzepatide (TZP) has demonstrated efficacy for glycemic control and weight loss in subjects with type 2 diabetes (T2D). However, previous clinical trials were not conducted under the treatment of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a background regimen nor were they limited to subjects with chronic kidney disease (CKD). OBJECTIVES: We evaluated the glycemic control of tirzepatide switching from conventional GLP-1 receptor agonists in subjects with T2D and CKD. DESIGN: This was a prospective, two-arm, observational study performed at a single center. METHODS: Eligible subjects were individuals with T2D and CKD who had been treated with dulaglutide for more than 3 months, with glycated hemoglobin (HbA1c) ⩾7.0%, and an estimated glomerular filtration rate ⩽60 mL/min/1.73 m. Subjects who switched to tirzepatide (TZP group) and those who continued dulaglutide (Dula group) were observed over 6 months. The primary outcome was a change in HbA1c over 6 months between the groups. Additional metabolic parameters, including body weight and the urine albumin-creatinine ratio (UACR), were evaluated. Adverse events in the TZP group were also investigated. RESULTS: Of the 55 participants, 48 completed the study (TZP group,  = 23; Dula group,  = 25). Tirzepatide significantly reduced HbA1c and body weight compared with the Dula group over 6 months (both  < 0.01). UACR levels remained stable in the TZP group throughout the study period and increased significantly in the Dula group ( < 0.05). Gastrointestinal events and hypoglycemia were observed in the TZP group, and those subjects who suffered hypoglycemic symptoms were mostly insulin users. CONCLUSION: Tirzepatide might be an effective alternative treatment for subjects with T2D and CKD who did not achieve sufficient glycemic control with conventional GLP-1RAs, as well as preventing the progression of nephropathy. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (registration number UMIN 000051344, date: June 16, 2023). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_his_list.cgi?recptno=R000058576.