Weight loss in patients with type 2 diabetes receiving once‐weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: A post‐hoc analysis of the AWARD‐4 study across baseline body mass index subgroups

Abstract

Aims: Insulin-treated patients with type 2 diabetes (T2D) and obesity are challenged in achieving body weight stability or reduction, in addition to glycaemic control. Post-hoc analyses of body weight and insulin dose data from the AWARD-4 trial involved comparison of treatment with once-weekly dulaglutide 1.5 mg (N = 295) or 0.75 mg (N = 293) and treatment with daily insulin glargine (N = 296), each with prandial insulin lispro (± metformin).Materials and methods: Changes in weight and in the proportion of patients without weight gain or with weight loss of at least 3%, 5% or 10% or composites of HbA1c less than 7% without weight gain and weight loss of at least 3% after 52 weeks were compared between the dulaglutide (either dose) groups and the insulin glargine group, overall and by baseline BMI (<30, 30-<35, ≥35 kg/m 2 ), using analysis of covariance and logistic regression, including interaction terms. Results:The following parameters were statistically significant (P < 0.01) in favour of the dulaglutide-treated groups, at lower mean total daily insulin doses, vs the insulin glargine group.The achieved targets were more pronounced with dulaglutide 1.5 mg than with insulin glargine: LSM weight change difference, −3.23 kg; proportion of patients without weight gain, 49.0% vs 19.0%; proportion of patients with weight loss ≥3%, 21.7% vs 5.7% or with weight loss ≥5%, 10.5% vs 2.4%; proportion of patients with HbA1c <7% without weight gain, 26.2% vs 7.9%;proportion of patients with HbA1c <7% and weight loss ≥3%, 11.9% vs 1.4%, respectively. Treatment effect for these parameters was not significantly different across BMI categories.Conclusions: Larger proportions of patients in late-stage T2D needing treatment intensification achieved glycemic control without weight gain or with weight loss at lower insulin doses with once-weekly dulaglutide plus daily prandial insulin than with a basal-bolus insulin regimen, overall and across all three BMI subgroups.

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

“…In these analyses, greater weight loss was observed with increasing baseline BMI for both semaglutide and dulaglutide, aligning with what has been previously reported for semaglutide 23 and dulaglutide. 35 While percentage weight loss was also greater with semaglutide versus dulaglutide, the percentage change in weight loss was generally of a similar magnitude across BMI categories, indicating that the weight-loss pattern observed across the HbA 1c subgroup categories may be associated with subjects' baseline BMI. High BMI is associated with an insulin-resistant phenotype in some patients, 3 and less weight loss is observed in patients with diabetes who are insulin resistant than in those with insulin sensitivity.…”

“…21 22 Post hoc analyses of the SUSTAIN and the AWARD trials have analysed patient subgroups across the continuum of T2D care. [23][24][25][26][27][28][29][30][31][32][33][34][35] Such analyses showed consistent, clinically relevant reductions in glycated haemoglobin (HbA 1c ) and body weight (BW) with semaglutide across patient subgroups based on characteristics including age, baseline body mass index (BMI), baseline HbA 1c , diabetes duration, race and ethnicity. 23-26 28 Dulaglutide has also been shown to be efficacious across subgroups based on sex, age, duration of diabetes, beta-cell function, HbA 1c , BW and BMI.…”

“…23-26 28 Dulaglutide has also been shown to be efficacious across subgroups based on sex, age, duration of diabetes, beta-cell function, HbA 1c , BW and BMI. [29][30][31][32][33][34][35] In the phase 3b SUSTAIN 7 clinical trial, semaglutide and dulaglutide were compared head-to-head in subjects with T2D on background treatment with metformin. 36 The trial showed superior reductions in HbA 1c and BW with semaglutide versus dulaglutide, for both low-dose (semaglutide 0.5 mg vs dulaglutide 0.75 mg) and highdose (semaglutide 1.0 mg vs dulaglutide 1.5 mg) comparisons.…”

Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial

“…A chronic inflammatory state linked to obesity leads to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors, which disrupt vascular homeostasis and contribute to endothelial vasodilator dysfunction by determining, among other effects, an imbalance in the endothelin-1/nitric oxide pathway [46]. Considering these premises, the reduction of body weight and BMI observed in the dulaglutide arm at the nine-month follow-up might lead to a reduction in the systemic inflammatory state, the resumption of the correct mechanisms of vascular homeostasis and, as observed in our trial, an improvement in the vascular health indexes.…”

Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: A randomized trial.

“…A previous study (47) demonstrated that the reduction of FPG and improvement in glycaemic variability are correlated with the reduction of oxidative stress on the vascular endothelium.…”