Johan Jendle1, Marcia A Testa2, Sherry Martin3, Honghua Jiang3, Zvonko Milicevic4. 1. Faculty of Medical Sciences, Department of Medicine, Örebro University, Örebro, Sweden. 2. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts. 3. Eli Lilly and Company, Indianapolis, Indiana. 4. Eli Lilly and Company Regional Operations, Vienna, Austria. milicevic_zvonko@lilly.com.
Abstract
AIM: To conduct a substudy, using 24-hour continuous glucose monitoring (CGM), of the AWARD-4 trial, which was designed to compare insulin + glucagon-like peptide-1 receptor agonist treatment with an insulin-only regimen. METHODS: The AWARD-4 trial randomized 884 conventional insulin regimen-treated patients to dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM substudy included 144 patients inserted with a Medtronic CGMS iPro CGM device to enable 3-day glucose monitoring. CGM sessions were completed at weeks 0, 13, 26 and 52. CGM measures included mean 24-hour glucose, percentage time in target glucose ranges, hyper- and hypoglycaemia and glucose variability. The primary objective was treatment comparison for percentage time spent with CGM glucose values in the 3.9-7.8 mmol/L range after 26 weeks. RESULTS: At week 26, mean CGM values decreased in all treatment groups (change from baseline -2.8 ± 0.3, -2.4 ± 0.3 and -2.5 ± 0.3 mmol/L for dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, respectively); between-group differences were not statistically significant. Treatment groups were similar for percentage time in the 3.9-7.8 mmol/L range. Percentage time in the 3.9-10.0 mmol/L range was greater for dulaglutide 1.5 mg than for glargine (p < 0.05). Dulaglutide and glargine were associated with decreased glucose variability for all CGM variability indices. The overall within-patient standard deviation (s.d.) was significantly reduced with dulaglutide 1.5 mg versus glargine (p < 0.05). At week 52, there were no significant differences among the groups with regard to measures of normoglycaemia or near-normoglycaemia and for the overall within-patient s.d. Treatment with glargine was associated with greater increases in percentage time spent with glucose values ≤3.9 mmol/L, with statistically significant differences between the groups at 52 weeks (p < 0.05). CONCLUSIONS: In combination with prandial lispro, treatment with dulaglutide and glargine resulted in similar proportions of glucose values in the normoglycaemic range, but dulaglutide provided an improved balance between the proportion of values within the near-normoglycaemia range and values within the hypoglycaemic range.
RCT Entities:
AIM: To conduct a substudy, using 24-hour continuous glucose monitoring (CGM), of the AWARD-4 trial, which was designed to compare insulin + glucagon-like peptide-1 receptor agonist treatment with an insulin-only regimen. METHODS: The AWARD-4 trial randomized 884 conventional insulin regimen-treated patients to dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM substudy included 144 patients inserted with a Medtronic CGMS iPro CGM device to enable 3-day glucose monitoring. CGM sessions were completed at weeks 0, 13, 26 and 52. CGM measures included mean 24-hour glucose, percentage time in target glucose ranges, hyper- and hypoglycaemia and glucose variability. The primary objective was treatment comparison for percentage time spent with CGM glucose values in the 3.9-7.8 mmol/L range after 26 weeks. RESULTS: At week 26, mean CGM values decreased in all treatment groups (change from baseline -2.8 ± 0.3, -2.4 ± 0.3 and -2.5 ± 0.3 mmol/L for dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, respectively); between-group differences were not statistically significant. Treatment groups were similar for percentage time in the 3.9-7.8 mmol/L range. Percentage time in the 3.9-10.0 mmol/L range was greater for dulaglutide 1.5 mg than for glargine (p < 0.05). Dulaglutide and glargine were associated with decreased glucose variability for all CGM variability indices. The overall within-patient standard deviation (s.d.) was significantly reduced with dulaglutide 1.5 mg versus glargine (p < 0.05). At week 52, there were no significant differences among the groups with regard to measures of normoglycaemia or near-normoglycaemia and for the overall within-patient s.d. Treatment with glargine was associated with greater increases in percentage time spent with glucose values ≤3.9 mmol/L, with statistically significant differences between the groups at 52 weeks (p < 0.05). CONCLUSIONS: In combination with prandial lispro, treatment with dulaglutide and glargine resulted in similar proportions of glucose values in the normoglycaemic range, but dulaglutide provided an improved balance between the proportion of values within the near-normoglycaemia range and values within the hypoglycaemic range.
Authors: Maria Isabel Del Olmo-García; David Hervás Marín; Jana Caudet Esteban; Antonio Ballesteros Martin-Portugués; Alba Cerveró Rubio; Miguel Angel Arnau Vives; Ana Catalá Gregori; Maite Penalba Martínez; Juan Francisco Merino-Torres Journal: J Int Med Res Date: 2020-06 Impact factor: 1.671