Safety and efficacy analyses across age and body mass index subgroups in East Asian participants with type 2 diabetes in the phase 3 tirzepatide studies (SURPASS programme)

Abstract

Aim: To assess the safety and efficacy of tirzepatide in people of East Asian descent based on age and body mass index (BMI).

Materials and methods: Data of participants enrolled in East Asian countries in the SURPASS-1, -3, -4, -5, J-mono and J-combo phase 3 clinical trials were included. Participants with type 2 diabetes with a baseline HbA1c of 7.0% up to 11.0% and a BMI of 23 kg/m² or greater or 25 kg/m² or greater were included. Participants treated with tirzepatide 5, 10 or 15 mg were evaluated to assess the safety and efficacy of tirzepatide in people of East Asian descent (94% from Japan) based on age (< 65 and ≥ 65 years) and BMI (< 25 and ≥ 25 kg/m² ). Key safety and efficacy outcomes were assessed.

Results: At baseline, 73% of East Asian participants had a BMI of 25 kg/m² or greater and 74% were younger than 65 years. At week 52, tirzepatide induced a similar dose-dependent reduction in HbA1c, waist circumference and BMI across subgroups. Across all BMI and age subgroups, mean absolute HbA1c reductions across the three doses ranged from 2.3% to 3.0%, and mean waist circumference reductions ranged from 4.3 to 9.8 cm. Improvements in absolute insulin sensitivity, assessed by homeostatic model assessment for insulin resistance, were greater in those with a baseline BMI of ≥ 25 kg/m² . Improvements in lipid profiles were similar across subgroups. While the safety profile of tirzepatide was broadly similar across BMI and age subgroups, drug discontinuation because of adverse events was higher in participants with a baseline age of ≥ 65 years.

Conclusions: This post hoc analysis showed that once-weekly tirzepatide had a similar safety and efficacy profile across BMI and age subgroups in East Asian participants.

Keywords: GIP; GLP-1; clinical trial; incretin therapy; population; study; type 2 diabetes.