Impact of patient characteristics on efficacy and safety of once-weekly semaglutide versus dulaglutide: SUSTAIN 7 post hoc analyses

Abstract

Objective: In SUSTAIN 7, once-weekly semaglutide demonstrated superior glycated haemoglobin (HbA_1c) and body weight (BW) reductions versus once-weekly dulaglutide in subjects with type 2 diabetes (T2D). This post hoc analysis investigated the impact of clinically relevant subject characteristics on treatment effects of semaglutide versus dulaglutide.

Design: Analyses by baseline age (<65, ≥65 years), sex (male, female), diabetes duration (≤5, >5-10, >10 years), HbA_1c (≤7.5, >7.5-8.5, >8.5% (≤58, >58-69, >69 mmol/mol)) and body mass index (BMI) (<30, 30-<35, ≥35 kg/m²).

Setting: 194 sites; 16 countries.

Participants: Subjects with T2D (n=1199) exposed to treatment.

Interventions: Semaglutide 0.5 mg versus dulaglutide 0.75 mg (low-dose comparison); semaglutide 1.0 mg versus dulaglutide 1.5 mg (high-dose comparison), all subcutaneously once weekly.

Primary and secondary outcome measures: Change in HbA_1c (primary endpoint) and BW (confirmatory secondary endpoint) from baseline to week 40; proportion of subjects achieving HbA_1c targets (<7%, ≤6.5% (<53, ≤48 mmol/mol)) and weight-loss responses (≥5%, ≥10%) at week 40; and safety.

Results: HbA_1c and BW reductions (estimated treatment difference ranges: -0.22 to -0.70%-point; -1.76 to -3.84 kg) and proportion of subjects achieving HbA_1c targets and weight-loss responses were statistically significantly greater for the majority of comparisons of semaglutide versus dulaglutide within each subgroup category and, excepting glycaemic control within the low-dose comparison in HbA_1c subgroups, this was irrespective of subgroup or dose comparison. Gastrointestinal adverse events, the most common with both treatments, were reported by more women than men and, with semaglutide, decreased with increasing BMI.

Conclusions: Consistently greater improvements in HbA_1c and BW with semaglutide versus dulaglutide, regardless of age, sex, diabetes duration, glycaemic control and BMI, support the efficacy of semaglutide across the continuum of care in a heterogeneous population with T2D.

Trial registration number: NCT02648204.

Keywords: clinical trials; diabetes & endocrinology; general diabetes.

Figure 1

Proportion of subjects achieving HbA_1c <7.0% (53 mmol/mol; A, C, E, G and I) and HbA_1c ≤6.5% (48 mmol/mol; B, D, F, H and J) at 40 weeks. *P<0.05, **p<0.001, ***p<0.0001. Values are estimated proportions from ANCOVAs with multiple imputations using ‘on-treatment without rescue medication’ data from all randomised subjects exposed to at least one dose of trial product as randomised (full analysis set) obtained while on treatment and prior to onset of rescue medication. P values are based on ETDs; statistical analyses were not performed for change from baseline. ANCOVAs, analysis of covariances; BMI, body mass index; ETDs, estimated treatment differences; HbA_1c, glycated haemoglobin.

Figure 2

Proportion of subjects achieving weight loss ≥5% (A, C, E, G and I) and weight loss ≥10% (B, D, F, H and J) at 40 weeks. *P<0.05, **p<0.001, ***p<0.0001. Values are estimated proportions from ANCOVAs with multiple imputations using ‘on-treatment without rescue medication’ data from all randomised subjects exposed to at least one dose of trial product as randomised (full analysis set) obtained while on treatment and prior to onset of rescue medication. P values are based on ETDs; statistical analyses were not performed for change from baseline. ANCOVAs, analysis of covariances; BMI, body mass index; ETDs, estimated treatment differences; HbA_1c, glycated haemoglobin.

Figure 3

Estimated treatment differences (ETDs) for change from baseline in HbA_1c shown as %-points (A), HbA_1c shown as mmol/mol (B) and body weight (C) at week 40 by age, sex, diabetes duration, HbA_1c and BMI at baseline. *P<0.05, **p<0.001, ***p<0.0001; †P values represent the test for treatment by subgroup interaction. Values are ETDs (95% CIs) for semaglutide versus dulaglutide (low-dose comparison (semaglutide 0.5 mg vs dulaglutide 0.75 mg) and high-dose comparison (semaglutide 1.0 mg vs dulaglutide 1.5 mg)) from ANCOVAs with multiple imputations using data from all randomised subjects exposed to at least one dose of trial product who did not discontinue treatment or receive any non-investigational antihyperglycaemic treatment (full analysis set) while on treatment and prior to onset of rescue medication. ANCOVA controlled for baseline HbA_1c (A and B) or body weight (C) and interaction between randomised treatment and subgroup. ANCOVA, analysis of covariance; BMI, body mass index; CI, confidence interval; ETD, estimated treatment difference; HbA_1c, glycated haemoglobin.