Real-world effectiveness and safety of low-dose tirzepatide in Japanese people with type 2 diabetes: a multicenter, retrospective, single-arm, observational study—East Shizuoka Tirzepatide (ESTATE) study

Abstract

The glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide is available clinically. Although real-world studies of tirzepatide in Japanese people with type 2 diabetes (T2D) have been reported, data regarding low-dose tirzepatide and patient-reported outcomes in routine clinical practice remain limited. In this multicenter retrospective observational study, we evaluated changes in glycemic control, body mass index (BMI), metabolic parameters, patient-reported outcomes, and adverse events after initiation of low-dose tirzepatide in Japanese people with T2D. Eighty-eight subjects with T2D treated with an average dose of tirzepatide of 4.5 ± 1.0 mg/week for 24 weeks were retrospectively analyzed. The primary outcomes were changes in glycated hemoglobin (HbA1c) and BMI from baseline to 24 weeks. HbA1c levels and BMI decreased over 24 weeks after initiation of low-dose tirzepatide (HbA1c, –1.5%; BMI, –1.5 kg/m²; both p < 0.001). Additionally, serum albumin was increased, and alanine transaminase and low-density lipoprotein cholesterol were decreased significantly. In multivariable regression analysis, higher baseline HbA1c was associated with greater HbA1c reduction. In exploratory cross-sectional analyses, post-treatment Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores were associated with higher baseline HbA1c, and Kanden Institute Stigma Scale (KISS) scores were associated with higher baseline BMI. Major adverse events linked with tirzepatide were gastrointestinal symptoms. In this multicenter retrospective single-arm observational study, HbA1c and BMI decreased over 24 weeks after low-dose tirzepatide initiation in Japanese people with T2D. These findings suggest that low-dose tirzepatide may be a useful treatment option in selected patients in routine clinical practice, although causal inference is limited by the observational design and lack of a control group.

Trial Registration: National University Hospital Medical Information Network (UMIN Clinical Trial Registry, UMIN000053671; approval date: March 1, 2024).