Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2)

Abstract

Introduction: To evaluate efficacy and safety data of dulaglutide in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with 1-2 oral antihyperglycemic medications (OAMs).

Methods: This is a subgroup analysis of a phase 3, open-label, randomized, parallel-arm, 52-week study in Chinese patients aged ≥ 18 years with T2DM who had inadequate glycemic control with OAMs (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤ 11.0%). The primary endpoint was assessment of the noninferiority of dulaglutide 1.5 mg as measured by change in HbA1c, compared with insulin glargine (glargine), using a 0.4% noninferiority margin at week 26.

Results: A total of 607 patients from China were randomized 1:1:1 to once-weekly dulaglutide 1.5 or 0.75 mg or once-daily glargine. At week 26, the least squares mean (LSM) change from baseline in HbA1c was greater with dulaglutide 1.5 mg (- 1.67%) and dulaglutide 0.75 mg (- 1.31%) compared with glargine (- 1.11%). The LSM (95% confidence interval) for the difference of dulaglutide 1.5 mg and 0.75 mg vs glargine was - 0.56% (- 0.75 to - 0.37) and - 0.20% (- 0.39 to - 0.01), respectively. Both doses of dulaglutide were noninferior and superior to glargine at 26 weeks and 52 weeks (two-sided P value < 0.05). The mean body weight decreased (P < 0.001) and total hypoglycemia rates were lower (P < 0.05) in the dulaglutide groups compared with the glargine group. Gastrointestinal adverse events (AEs) were the most frequently reported AEs in dulaglutide groups.

Conclusion: Both doses of dulaglutide are efficacious and tolerable in Chinese patients with T2DM who had inadequate glycemic control on OAMs.

Trial registration: ClinicalTrials.gov identifier, NCT01648582.

Funding: Eli Lilly and Company.

Keywords: China; Dulaglutide; Glucagon-like peptide-1 receptor agonist; Glycated hemoglobin; Type 2 diabetes mellitus.

Figures

Fig. 1

Study design. DU dulaglutide, GLP-1 glucagon-like peptide-1, LV30 post-study therapy safety follow-up visit, Met metformin, RA receptor agonist, SU sulfonylurea

Fig. 2

Patient disposition. †Cumulative total of all patients who discontinued the study up to week 52. N total population, n number of patients in each category

Fig. 3

Efficacy and safety outcome measures. a LSM (SE) change in HbA1c (%) from baseline to 26 weeks and to 52 weeks. †LSM difference (95% CI) of dulaglutide 1.5 mg with glargine. ‡LSM difference (95% CI) of dulaglutide 0.75 mg with glargine. *Dulaglutide noninferior to glargine (two-sided P value < 0.001). #Dulaglutide superior to glargine (two-sided P value < 0.05). CI confidence interval, DU dulaglutide, HbA1c glycated hemoglobin, LSM least squares mean, SE standard error. b LSM (SE) change in HbA1c (%) from baseline over time. c Percentage of patients achieving HbA1c targets at week 26 and at week 52. *P < 0.001 dulaglutide vs glargine. #P < 0.05 dulaglutide vs glargine. d LSM (SE) change in fasting serum glucose (mmol/L) from baseline to week 26 and to week 52. †LSM difference (95% CI) of dulaglutide 1.5 mg with glargine. ‡LSM difference (95% CI) of dulaglutide 0.75 mg with glargine. *P < 0.05 dulaglutide vs glargine. FSG fasting serum glucose. 7-point self-monitored blood glucose profiles (mmol/L) by time of day at the end of e week 26 and f week 52. *P < 0.05 dulaglutide vs glargine. #P < 0.05 glargine vs dulaglutide. hr hour, PP postprandial, SMBG self-monitored blood glucose. g LSM (SE) change in body weight (kg) from baseline to 52 weeks. *P < 0.001 dulaglutide 1.5 mg vs glargine. #P < 0.001 dulaglutide 0.75 mg vs glargine. h Summary of occurrence of gastrointestinal treatment-emergent adverse events

Fig. 3

Efficacy and safety outcome measures. a LSM (SE) change in HbA1c (%) from baseline to 26 weeks and to 52 weeks. †LSM difference (95% CI) of dulaglutide 1.5 mg with glargine. ‡LSM difference (95% CI) of dulaglutide 0.75 mg with glargine. *Dulaglutide noninferior to glargine (two-sided P value < 0.001). #Dulaglutide superior to glargine (two-sided P value < 0.05). CI confidence interval, DU dulaglutide, HbA1c glycated hemoglobin, LSM least squares mean, SE standard error. b LSM (SE) change in HbA1c (%) from baseline over time. c Percentage of patients achieving HbA1c targets at week 26 and at week 52. *P < 0.001 dulaglutide vs glargine. #P < 0.05 dulaglutide vs glargine. d LSM (SE) change in fasting serum glucose (mmol/L) from baseline to week 26 and to week 52. †LSM difference (95% CI) of dulaglutide 1.5 mg with glargine. ‡LSM difference (95% CI) of dulaglutide 0.75 mg with glargine. *P < 0.05 dulaglutide vs glargine. FSG fasting serum glucose. 7-point self-monitored blood glucose profiles (mmol/L) by time of day at the end of e week 26 and f week 52. *P < 0.05 dulaglutide vs glargine. #P < 0.05 glargine vs dulaglutide. hr hour, PP postprandial, SMBG self-monitored blood glucose. g LSM (SE) change in body weight (kg) from baseline to 52 weeks. *P < 0.001 dulaglutide 1.5 mg vs glargine. #P < 0.001 dulaglutide 0.75 mg vs glargine. h Summary of occurrence of gastrointestinal treatment-emergent adverse events

Fig. 3

Efficacy and safety outcome measures. a LSM (SE) change in HbA1c (%) from baseline to 26 weeks and to 52 weeks. †LSM difference (95% CI) of dulaglutide 1.5 mg with glargine. ‡LSM difference (95% CI) of dulaglutide 0.75 mg with glargine. *Dulaglutide noninferior to glargine (two-sided P value < 0.001). #Dulaglutide superior to glargine (two-sided P value < 0.05). CI confidence interval, DU dulaglutide, HbA1c glycated hemoglobin, LSM least squares mean, SE standard error. b LSM (SE) change in HbA1c (%) from baseline over time. c Percentage of patients achieving HbA1c targets at week 26 and at week 52. *P < 0.001 dulaglutide vs glargine. #P < 0.05 dulaglutide vs glargine. d LSM (SE) change in fasting serum glucose (mmol/L) from baseline to week 26 and to week 52. †LSM difference (95% CI) of dulaglutide 1.5 mg with glargine. ‡LSM difference (95% CI) of dulaglutide 0.75 mg with glargine. *P < 0.05 dulaglutide vs glargine. FSG fasting serum glucose. 7-point self-monitored blood glucose profiles (mmol/L) by time of day at the end of e week 26 and f week 52. *P < 0.05 dulaglutide vs glargine. #P < 0.05 glargine vs dulaglutide. hr hour, PP postprandial, SMBG self-monitored blood glucose. g LSM (SE) change in body weight (kg) from baseline to 52 weeks. *P < 0.001 dulaglutide 1.5 mg vs glargine. #P < 0.001 dulaglutide 0.75 mg vs glargine. h Summary of occurrence of gastrointestinal treatment-emergent adverse events