Real-World Effectiveness of Tirzepatide in Japanese Patients with Type 2 Diabetes: A Multicenter Retrospective Observational Study

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, significantly affects glucose and body weight-lowering effects in randomized controlled trials. However, real-world clinical evidence in Japan remains limited. This study aimed to evaluate the real-world effectiveness of tirzepatide on glycemic and metabolic factors in Japanese patients with type 2 diabetes mellitus (T2DM). In this multicenter, retrospective, observational study, we included patients with T2DM from seven Japanese institutions who received tirzepatide treatment for at least 24 weeks. Tirzepatide effectiveness was evaluated by comparing clinical and biochemical parameters, including glycated hemoglobin (HbA1c), plasma glucose levels, body weight, blood pressure, lipid profiles, liver enzyme levels, and renal function, before and after 24 weeks of treatment. We included 324 patients (mean age, 56.8 ± 11.4 years; median body mass index (BMI), 30.4 kg/m 2 (interquartile range 26.8–34.0)). At 24 weeks, 42 (13.0%), 211 (65.1%), 35 (10.8%), 25 (7.7%), and 11 (3.4%) patients received 2.5 mg, 5 mg, 7.5 mg, 10 mg, and 12.5/15 mg tirzepatide, respectively. HbA1c and body weight significantly decreased after tirzepatide administration; the median HbA1c and body weight reduced from 7.9% [7.2–8.6] to 6.8% [6.1–7.5] and from 82.5 kg [73.5–94.6] to 80.0 kg [70.9–92.5], respectively, whereas the medians of changes in HbA1c and body weight from baseline to week 24 were – 0.9% [– 1.6 to – 0.3] and – 2.0 kg [– 4.0 to 0.0] ( p < 0.001). HbA1c reduction was greater in GLP-1 receptor agonist-naïve patients ( p < 0.001). Changes in HbA1c levels significantly correlated with baseline HbA1c levels ( r s = – 0.473, p < 0.001), but not BMI. In real-world clinical practice, tirzepatide was associated with improvements in glycemic control and reductions in body weight in Japanese patients with T2DM, across diverse baseline therapies. These results suggest that tirzepatide may be a useful option across diverse treatment backgrounds, with greater observed benefits in GLP-1RA-naïve individuals with higher baseline HbA1c levels.