In a small 6‑month study of people with type‑2 diabetes and chronic kidney disease, switching from the GLP‑1 drug dulaglutide to tirzepatide lowered blood‑sugar (HbA1c) and body weight more than staying on dulaglutide, while kidney damage markers stayed steady. Some participants had stomach upset and a few insulin‑using folks experienced low blood‑sugar episodes.

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). We evaluated the glycemic control of tirzepatide switching from conventional GLP-1 receptor agonists in subjects with T2D and CKD. This was a prospective, two-arm, observational study performed at a single center. Eligible subjects were individuals with T2D and CKD who had been treated with dulaglutide for more than 3&#x2009;months, with glycated hemoglobin (HbA1c) &#x2a7e;7.0%, and an estimated glomerular filtration rate &#x2a7d;60&#x2009;mL/min/1.73&#x2009;m². Subjects who switched to tirzepatide (TZP group) and those who continued dulaglutide (Dula group) were observed over 6&#x2009;months. The primary outcome was a change in HbA1c over 6&#x2009;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. Of the 55 participants, 48 completed the study (TZP group, <i>n</i>&#x2009;=&#x2009;23; Dula group, <i>n</i>&#x2009;=&#x2009;25). Tirzepatide significantly reduced HbA1c and body weight compared with the Dula group over 6&#x2009;months (both <i>p</i>&#x2009;&lt;&#x2009;0.01). UACR levels remained stable in the TZP group throughout the study period and increased significantly in the Dula group (<i>p</i>&#x2009;&lt;&#x2009;0.05). Gastrointestinal events and hypoglycemia were observed in the TZP group, and those subjects who suffered hypoglycemic symptoms were mostly insulin users. 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. 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.