This was an exploratory evaluation of treatment satisfaction using data from the SURPASS J-mono clinical trial, a multicenter, randomized, double-blind, active-controlled, parallel-group phase 3 trial in Japanese patients with T2D, which assessed the efficacy and safety of tirzepatide (5, 10, and 15 mg) compared with dulaglutide 0.75 mg over 52 weeks. The study methods and main outcomes of the trial have been previously published [21]. In brief, participants were Japanese adults aged ≥ 20 years with a T2D diagnosis (WHO classification); were naïve to oral antihyperglycemic medication (OAM) or receiving OAM monotherapy (with the exception of thiazolidinedione) and willing to discontinue the OAM during an 8-week washout period; and had a stable weight (± 5%) for at least 3 months prior to visit 1, a body mass index (BMI) ≥ 23 kg/m2 at visit 1, and an HbA1c ≥ 7.0% to ≤ 10.0% at visits 1 and 2 (for OAM-naïve patients) or ≥ 6.5% to ≤ 9.0% at visit 1 and ≥ 7.0% to ≤ 10.0% at visit 2 (for patients discontinuing OAM). Patients were excluded if they had a diagnosis of type 1 diabetes or a history of any injectable therapy use for T2D, acute or chronic pancreatitis, acute or chronic hepatitis, or diabetic retinopathy requiring acute treatment.

The study was approved by an independent ethical review board at each site and was conducted in accordance with the Declaration of Helsinki 1964 and its later amendments and the Council for International Organizations of Medical Sciences international ethical guidelines. All patients provided written informed consent before study participation. The study was registered at ClinicalTrials.gov (NCT03861052).

Patients were randomly assigned in a 1:1:1:1 ratio to receive tirzepatide 5, 10, or 15 mg or dulaglutide 0.75 mg. Randomization was stratified on the basis of patients’ baseline HbA1c (≤ 8.5% or > 8.5%), baseline BMI (< 25 or ≥ 25 kg/m2), and need for OAM washout (yes or no). The study comprised a 4-week (for OAM-naïve patients) or 10-week (≥ 8-week washout for patients discontinuing OAM) screening/lead-in period, followed by a 52-week treatment period and a 4-week safety follow-up period. During the treatment period, patients received tirzepatide or dulaglutide once weekly by subcutaneous injection. The tirzepatide dose was initiated at 2.5 mg, increased by 2.5 mg every 4 weeks until the assigned dose was reached, and then maintained for the remainder of treatment.

Treatment satisfaction was a secondary outcome of the trial and was assessed using the Japanese translation of the DTSQ [8]. Two DTSQ versions were used to assess treatment satisfaction: the DTSQs at baseline and the DTSQc at weeks 40 and 52 and in cases of early termination [9, 10].

The DTSQ is a self-administered PRO instrument comprising eight items, which are conceptually similar for the DTSQs and DTSQc versions. Each item of the DTSQs is assessed on a 7-point Likert scale (0 to 6). For six of the eight items (items 1 [satisfaction with current treatment], 4 [convenience], 5 [flexibility], 6 [understanding of diabetes], 7 [recommend treatment to others], and 8 [willingness to continue]), scores range from 0 (very dissatisfied) to 6 (very satisfied) [6]. These scores are summed to provide a composite measure of overall treatment satisfaction, ranging from 0 to 36, with higher scores indicating greater satisfaction. Items 2 and 3 of the DTSQs are used to individually measure the perceived frequency of unacceptable hyperglycemia and hypoglycemia, respectively, with scores ranging from 0 (none of the time) to 6 (most of the time). The DTSQc has different response options from those of the DTSQs to produce a measure of the change from baseline in satisfaction rather than absolute satisfaction [10]. Each item of the DTSQc assesses change from baseline on a 7-point scale. Scores for DTSQc item 1 and items 4 to 8 range from − 3 (much less now) to + 3 (much more now), with overall treatment satisfaction scores (sum of scores on item 1 and items 4 through 8) ranging from − 18 to + 18 (higher scores represent greater satisfaction). Possible DTSQc scores for items 2 and 3 (perceived frequency of hyperglycemia and hypoglycemia, respectively) range from − 3 (much less of the time now) to + 3 (much more of the time now).

Analyses were performed on the modified intention-to-treat population of the efficacy analysis set, which included all randomly assigned patients who received at least one dose of study drug and excluded data after initiation of rescue antihyperglycemic medication or permanent study drug discontinuation. For the DTSQs, descriptive statistics are provided at baseline for the perceived hyperglycemia and hypoglycemia items and the six-item overall treatment satisfaction score. For the DTSQc, the proportion of responses (− 3 to + 3) for each item was summarized by treatment arm.

Treatment comparisons of least-squares means (standard error) of scores at week 52 were made between the tirzepatide and dulaglutide arms using a mixed model for repeated measures with treatment, visit, treatment-by-visit interaction, baseline HbA1c (≤ 8.5% or > 8.5%), baseline BMI (< 25 or ≥ 25 kg/m2), and need for OAM washout (yes or no) as fixed effects and baseline measurement as a covariate. An unstructured covariance matrix was used as the model of intrapatient variability.

Subgroup analyses were conducted for the DTSQc overall treatment satisfaction score at week 52, based on age (< 65 or ≥ 65 years), sex (male or female), baseline BMI (< 25 or ≥ 25 kg/m2), and baseline HbA1c (≤ 8.5% or > 8.5%), using an analysis of covariance model. The model included the same fixed effects and covariate as those used for the main analysis.

Analyses were conducted at a two-sided alpha level of 0.05. Statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). The DTSQ analyses were prespecified; however, all subgroup analyses were conducted post hoc. No multiplicity adjustment was conducted for the DTSQc.