Effect of once‐weekly dulaglutide on glycated haemoglobin (HbA1c) and fasting blood glucose in patient subpopulations by gender, duration of diabetes and baseline HbA1c

Abstract

AimsTo evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in patients with type 2 diabetes by subgroups of gender, duration of diabetes and baseline glycated haemoglobin (HbA1c) in the dulaglutide clinical development programme (AWARD‐1 to ‐6 and ‐8 clinical trials).MethodsChange in HbA1c was analysed by gender, duration of diabetes (<5, ≥5 years and <10, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia and gastrointestinal adverse events were evaluated for individual trials.ResultsIn the pooled analysis of patients treated with dulaglutide 1.5 mg at 6 months, the reductions in HbA1c from baseline were similar across gender (men: least squares [LS] mean −1.26% [95% confidence interval {CI} −1.36, −1.16]; women: LS mean −1.33% [95% CI −1.43, −1.24]) and among duration of diabetes subgroups (<5 years: LS mean −1.32% [95% CI −1.43, −1.22]; ≥5 and <10 years: LS mean −1.33% [95% CI −1.43, −1.22]; ≥10 years: −1.24% [95% CI −1.35, −1.14]). Patients with baseline HbA1c ≥8.5% had greater HbA1c reductions than patients with baseline HbA1c <8.5%, (≥8.5%: LS mean −1.86% [95% CI −1.97, −1.75]; <8.5%: LS mean −1.02% [95% CI −1.12, −0.93]). Reductions in fasting blood glucose (FBG) were consistent with HbA1c changes. Similar results were observed with dulaglutide 0.75 mg. In general, body weight changes were similar among duration of diabetes and in baseline HbA1c subgroups, respectively; women had a numerically greater weight loss or less weight gain than men with both dulaglutide doses. There was no clinically meaningful difference in hypoglycaemia trends by gender or duration of diabetes. Hypoglycaemia incidence and rate were generally lower in patients with baseline HbA1c ≥8.5% than in those with <8.5%, except for the AWARD‐4 study (combination with mealtime insulin).ConclusionsAcross the AWARD studies, dulaglutide demonstrated significant improvements in glycaemic control irrespective of gender, duration of diabetes, or baseline HbA1c, with greater HbA1c and FBG reductions in patients with a higher baseline HbA1c. Dulaglutide was well tolerated, with a safety profile similar to other glucagon‐like peptide‐1 receptor agonists.

Impact of baseline characteristics and beta‐cell function on the efficacy and safety of subcutaneous once‐weekly semaglutide: A patient‐level, pooled analysis of the SUSTAIN 1‐5 trials

“…Across the range of baseline HbA1c subgroups in this analysis, subjects with higher HbA1c values at baseline had the greatest reductions in HbA1c , with a statistically significant effect of baseline HbA1c in the semaglutide 1.0 mg treatment arm ( P < 0.05). Baseline HbA1c is a well‐established predictor of glycaemic response for all antidiabetes treatments, even for non‐pharmacological interventions; this finding is consistent with published findings for other GLP‐1RAs, including dulaglutide, liraglutide and lixisenatide . Importantly, from the clinical perspective, these observed differences in the magnitude of change from baseline in HbA1c across HbA1c subgroups resulted in a similar mean end‐of‐treatment HbA1c level.…”

“…Subjects with the highest HbA1c at baseline lost less weight than those with lower HbA1c at baseline, albeit with clinically relevant absolute weight loss. A similar pattern, with less weight loss in subjects with higher baseline HbA1c levels, was also observed with dulaglutide in the AWARD programme, and with liraglutide . These findings may be a result of treatment‐related increases in glycaemic control.…”

Efficacy and safety of subgroup analysis stratified by baseline HbA1c in a Japanese phase 3 study of dulaglutide 0.75 mg compared with insulin glargine in patients with type 2 diabetes

“…This is because there is a greater potential for improvement in glycemic control in patients with higher baseline HbA1c. Similar relationships between baseline HbA1c levels and improvements in glycemic control have also been seen in previous reports of meta-analyses of various glucose-lowering therapies [13], meta-analyses of GLP-1 receptor agonists other than dulaglutide [14,15], and global phase 3 studies of dulaglutide [16].…”

Effect of once weekly dulaglutide by baseline beta‐cell function in people with type 2 diabetes in the AWARD programme

“…Dulaglutide, a once‐weekly GLP‐1RA approved for the treatment of T2D, has been evaluated in the Assessment of Weekly AdministRation of LY2189265 in Diabetes (AWARD) clinical development programme. In these clinical studies, dulaglutide significantly reduced higher baseline glycated haemoglobin (HbA1c) irrespective of age, gender, ethnicity, duration of diabetes, body mass index (BMI), body weight at baseline, or HbA1c, with a greater effect observed in patients with higher baseline HbA1c …”

“…In these clinical studies, dulaglutide significantly reduced higher baseline glycated haemoglobin (HbA1c) irrespective of age, gender, ethnicity, duration of diabetes, body mass index (BMI), body weight at baseline, or HbA1c, with a greater effect observed in patients with higher baseline HbA1c. 13,14 The aim of this study was to investigate whether beta-cell function status at baseline measured by HOMA2-%B affects the glycaemic response to dulaglutide. Patients with T2D enrolled in three clinical trials from the AWARD programme (AWARD-1, AWARD-3, and AWARD-6) were included in the analysis.…”