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/m 2 or greater or 25 kg/m 2 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/m 2 ). Key safety and efficacy outcomes were assessed.Results: At baseline, 73% of East Asian participants had a BMI of 25 kg/m 2 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/m 2 . 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.

Efficacy and safety of tirzepatide in people with type 2 diabetes by baseline body mass index: An exploratory subgroup analysis of SURPASS‐AP‐Combo

“…In the present analysis, a consistent beneficial effect of tirzepatide on lipid profiles was observed across the BMI subgroups, with the greatest improvement observed in participants with a BMI of 30 kg/m 2 or higher. These results are largely consistent with those from an East Asian post hoc analysis of data from the SURPASS programme, which reported improvements in lipid profiles with tirzepatide across patient subgroups by BMI (<25 and ≥25 kg/m 2 ) and age (<65 and ≥65 years) 24 . It should be noted that, in our study, participants with a BMI of 30 kg/m 2 or higher tended to also be younger with a shorter duration of diabetes.…”

“…The results of the post hoc analyses also showed that tirzepatide impacted cardiovascular risk factors across a range of baseline BMIs, with tirzepatide treatment leading to moderate reductions in SBP and a mild reduction in DBP from baseline to Week 40 across all BMI subgroups. These results are consistent with a previous post hoc analysis of East Asian participants included in the global SURPASS programme categorized by BMI (<25 and ≥25 kg/m 2 ) and age (<65 and ≥65 years) 24 . Interestingly, mediation analyses of SURPASS 1–5 indicated that tirzepatide‐induced SBP reduction was primarily mediated through weight reduction 25 .…”

“…Asian post hoc analysis of data from the SURPASS programme, which reported improvements in lipid profiles with tirzepatide across patient subgroups by BMI (<25 and ≥25 kg/m 2 ) and age (<65 and ≥65 years). 24 It should be noted that, in our study, participants with a BMI of 30 kg/ m 2 or higher tended to also be younger with a shorter duration of diabetes. Interestingly, the results of a post hoc analysis of a Phase 2 study showed that tirzepatide improved atherogenic lipoprotein profile by decreasing large triglyceride-rich lipoprotein and small LDL particles, apoC-III (apolipoprotein C-III) and apoB (apolipoprotein B).…”

“…22 In all baseline BMI subgroups in this analysis, all doses of tirzepatide led to significant reduc- and ≥65 years). 24 Interestingly, mediation analyses of SURPASS 1-5 indicated that tirzepatide-induced SBP reduction was primarily mediated through weight reduction. 25 However, further studies are needed to fully understand the effect of tirzepatide on SBP and DBP.…”

Incidence and predictors of remission and relapse of type 2 diabetes mellitus in Japan: Analysis of a nationwide patient registry (JDDM73)

“…The phenomenon of improvement of glucose to levels in a normal range and cessation of the need for medication can occur in some patients diagnosed with type 2 diabetes who are provided with lifestyle therapy, temporary pharmacotherapy, bariatric surgery, or combinations of these treatments, in both randomized controlled trials and clinical practice. [1][2][3][4][5][6][7][8][9] An international expert group described this phenomenon as "remission of diabetes" in a consensus report. 10 However, this phenomenon is not yet fully understood in routine care settings, and many factors remain to be clarified.…”