Dataset Information

Efficacy and Safety of Once-Weekly Dulaglutide in Type 2 Diabetes Patients Using Insulin: Exploratory Subgroup Analysis by Insulin Regimen.

ABSTRACT: PURPOSE:In East Asian patients, type 2 diabetes mellitus (T2DM) is characterized primarily by β-cell dysfunction, with lower insulin secretion than in Caucasian individuals. Therefore, bolus insulin and premixed insulin containing a bolus insulin component are important therapeutic tools in Japan, in addition to basal insulin. This subgroup analysis is stratified by insulin regimen and uses data from a phase 4, randomized, placebo-controlled, double-blind and subsequent open-label study in Japan to assess the efficacy and safety of once-weekly dulaglutide combined with various insulin therapies. METHODS:This multicenter study enrolled Japanese patients with T2DM and inadequate glycemic control [glycated hemoglobin A1c (HbA1c) ≥ 7.5% to ≤ 10.5%] on insulin therapy [basal (B), premixed (PM), or basal bolus (BB)] in combination with or without one or two oral antidiabetic agents. Randomized participants received once-weekly dulaglutide 0.75 mg (n = 120) or placebo (n = 39) during a 16-week double-blind treatment period, and dulaglutide during a 36-week open-label extension. In this subgroup analysis, efficacy measures were changes from baseline in HbA1c, 7-point self-monitored blood glucose profiles, and body weight. Safety measures were incidence of adverse events and hypoglycemia during the first 16 weeks. RESULTS:At week 16, least squares mean differences (95% CI) regarding changes from baseline in HbA1c for each insulin regimen versus placebo were: B: - 1.62% (- 1.96, - 1.28), PM: - 1.78% (- 2.25, - 1.30), and BB: - 1.15% (- 1.54, - 0.77); p < 0.001 dulaglutide vs. placebo for each subgroup. No significant differences in body weight changes were observed between dulaglutide and placebo for any insulin regimen. Gastrointestinal symptoms were the most commonly observed adverse events in dulaglutide-treated patients. Hypoglycemia incidence rates were: B: dulaglutide 38.5% vs. placebo 23.5%; PM: dulaglutide 38.5% vs. placebo 44.4%; BB: dulaglutide 50.0% vs. placebo 30.8%. CONCLUSIONS:Overall, dulaglutide was generally well tolerated and improved glycemic control significantly versus placebo, regardless of insulin regimen. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02750410.

SUBMITTER: Onishi Y

PROVIDER: S-EPMC7048887 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionThis subgroup analysis assessed the efficacy and safety of once weekly dulaglutide 1.5 mg and 0.75 mg in East Asian patients with type 2 diabetes (T2D) stratified by key demographic and baseline characteristics.MethodsChange from baseline in glycated hemoglobin (HbA1c), fasting blood glucose (FBG) and body weight were analyzed by age (< 60 years, ≥ 60 years), gender (male, female), body weight (< 70 kg, ≥ 70 kg), BMI (< 25 kg/m2, ≥ 25 kg/m2), duration of diabetes (< 10 years, ≥ 10 years), baseline HbA1c (< 8.5%, ≥ 8.5%) and concomitant oral antihyperglycemic medications (OAMs; metformin only, SU only, metformin + SU) at week 26 and 52 in East Asian patients from the AWARD-CHN2 study. Incidence of gastrointestinal adverse events (GI AEs) and hypoglycemia was evaluated.ResultsA total of 422 East Asian patients with T2D were included in this subgroup analysis. At week 26, the reduction of HbA1c and FBG from baseline were similar across subgroups, except that patients with baseline HbA1c ≥ 8.5% had greater HbA1c and FBG reductions than patients with baseline HbA1c < 8.5%. Gender analysis showed HbA1c difference that was not clinically significant. The decrease in body weight varied across different subgroups in both dulaglutide doses; however, the difference was not clinically significant. The incidence of GI AEs and total hypoglycemia was generally similar across subgroups in both doses. A similar trend was observed at week 52 in both dulaglutide doses.ConclusionsIn East Asian patients with T2D, treatment with dulaglutide (1.5 mg and 0.75 mg) demonstrated significant improvements in glycemic control irrespective of all subgroups, except baseline HbA1c, with greater HbA1c and FBG reductions in patients with higher baseline HbA1c. Dulaglutide was well tolerated with a similar safety profile to other GLP-1 receptor agonists.Trial registrationClinicalTrials.gov Identifier: NCT01648582.

Project description:IntroductionAlthough global studies have investigated the combination of dulaglutide with insulin in patients with type 2 diabetes mellitus (T2DM), differences in lean body mass and dulaglutide dosing can complicate the extrapolation of global study results to Japanese patients. This phase 4, randomized, placebo-controlled, double-blind, and subsequent open-label study aimed to assess the efficacy and safety of once-weekly dulaglutide 0.75 mg in combination with insulin therapy in patients with T2DM.MethodsPatients enrolled in this multicenter study were Japanese with T2DM who had inadequate glycemic control (HbA1c 7.5-10.5%) with insulin therapy (basal insulin, premixed insulin, or basal/mealtime insulin) in combination with or without one or two oral antidiabetic agents (OADs). Patients were randomized in a 3:1 ratio to dulaglutide or placebo. The first 16 weeks was the double-blind period with stable insulin dosing, and patients taking placebo were switched to dulaglutide for an additional 36-week open-label period in which all patients took dulaglutide (52 weeks total).ResultsPatients (N = 159) were randomized to dulaglutide (n = 120) or placebo (n = 39). The least-squares (LS) mean changes from baseline in HbA1c at week 16 were dulaglutide - 1.45% and placebo 0.06%. The LS mean and 95% confidence interval for the difference were - 1.50% (- 1.73%, - 1.28%) and dulaglutide was superior to placebo. There were no significant differences between treatment groups in changes from baseline in body weight and insulin dose. The most frequently observed treatment-emergent adverse events in dulaglutide were nasopharyngitis, constipation, abdominal discomfort, nausea, and decreased appetite. The incidence rates of hypoglycemic events by week 16 were dulaglutide 42.5% and placebo 30.8% (P = 0.258).ConclusionOnce-weekly dulaglutide 0.75 mg was superior to once-weekly placebo in glycemic control improvement and well tolerated in patients with T2DM in combination with insulin therapy with or without OADs.Trial registrationClinicalTrials.gov, NCT02750410.FundingEli Lilly and Company.

Project description:IntroductionIn the randomized, open-label, parallel-arm, active-controlled phase III AWARD-CHN2 trial, once-weekly dulaglutide plus concomitant oral antihyperglycemic medications (OAMs) improved HbA1c over 26 weeks compared with once-daily insulin glargine in patients with type 2 diabetes mellitus (T2DM). This post-hoc subgroup analysis of AWARD-CHN2 investigated the pancreatic safety of dulaglutide in Chinese patients with T2DM, stratified by potential influencing factors.MethodsChanges in pancreatic enzyme (pancreatic amylase, total amylase, and lipase) levels over 26 weeks were assessed and stratified by patient age (< 60, ≥ 60 years), sex (female, male), duration of diabetes (< 10, ≥ 10 years), baseline weight (< 70, ≥ 70 kg), BMI (< 25, ≥ 25 kg/m2), HbA1c (< 8.5, ≥ 8.5%), triglycerides (< 2.3, ≥ 2.3 mmol/L), and concomitant OAMs (metformin, sulfonylurea, metformin plus sulfonylurea).ResultsA total of 203 Chinese patients with T2DM were included in this post-hoc analysis. Pancreatic enzyme levels increased within the normal range from baseline to Week 26, and no pancreatitis events were confirmed by independent adjudication. Least-squares mean increase in pancreatic amylase (U/L) from baseline to Week 26 was comparable across all subgroups with no statistically (all P-values > 0.05) or clinically significant between-group differences for age (< 60 years: 5.34; ≥ 60 years: 6.71), sex (female: 5.85; male: 5.66), duration of diabetes (< 10 years: 6.15; ≥ 10 years: 4.85), weight (< 70 kg: 6.19; ≥ 70 kg: 5.39), BMI (< 25 kg/m2: 5.92; ≥ 25 kg/m2: 5.61), HbA1c (< 8.5%: 6.82; ≥ 8.5%: 4.08), triglycerides (< 2.3 mmol/L: 4.94; ≥ 2.3 mmol/L: 8.04), and concomitant OAMs (metformin: 5.68; sulfonylurea: 5.44; metformin plus sulfonylurea: 5.87). Similar results were observed for total amylase and lipase.ConclusionIn Chinese patients with T2DM receiving dulaglutide 1.5 mg in AWARD-CHN2, elevations of pancreatic enzymes over 26 weeks were within the normal range and were neither associated with pancreatitis nor baseline factors, which suggests the clinical use of dulaglutide in Chinese patients with T2DM is not associated with pancreatic safety issues.Clinical trial registrationNCT01648582.

Project description:INTRODUCTION:This analysis evaluated the efficacy and safety of dulaglutide in Chinese patients with type 2 diabetes (T2D) aged ??60 and <?60 years. METHODS:This post hoc analysis included patients with T2D enrolled in two phase 3 clinical trials AWARD-CHN1 (NCT01644500) and AWARD-CHN2 (NCT01648582) of dulaglutide 0.75 and 1.5 mg. Patients were categorized into two groups (??60 and <?60 years). Efficacy outcomes (change in glycated hemoglobin [HbA1c], fasting blood glucose [FBG], and weight; percentage of patients achieving HbA1c target [<?7.0%]) and safety outcomes (incidence of hypoglycemia and gastrointestinal treatment-emergent adverse events [GI TEAEs]) at 26 weeks were evaluated for each age group in both trials. RESULTS:A total of 766 patients (??60 years, n?=?222;?<?60 years, n?=?544) were included in the study. A similar reduction of HbA1c was observed in both age groups: AWARD-CHN1, 1.5 mg (least squares mean [LSM] 95% confidence interval [CI] ??60 years: -?1.45% [-?1.69, -?1.21%] and <?60 years: -?1.43% [-?1.59, -?1.28%]) and 0.75 mg (??60 years: -?1.29% [-?1.53, -?1.05%] and <?60 years: -?1.18% [-?1.33, -?1.03%]); AWARD-CHN2, 1.5 mg (??60 years: -?1.60% [-?1.83, -?1.36%] and <?60 years: -?1.64% [-?1.80, -?1.49%]) and 0.75 mg (??60 years: -?1.31% [-?1.55, -?1.08%] and <?60 years: -?1.33% [-?1.48, -?1.17%]). Dulaglutide showed a reduction in HbA1c as early as 4 weeks after initiation of treatment, which was maintained over 26 weeks in both age groups. The percentage of patients achieving HbA1c target?<?7.0% at 26 weeks was also similar in both age groups. Incidence of hypoglycemia and GI TEAEs was low in each age group. CONCLUSION:Treatment with once-weekly dulaglutide improved glycemic control in patients with T2D aged ??60 years and <?60 years and was well tolerated in older patients, suggesting it can be considered a safe and effective treatment option for use in older patients with T2D. TRIAL REGISTRATION:AWARD-CHN1 (NCT01644500) and AWARD-CHN2 (NCT01648582).

Project description:ObjectiveIn SUSTAIN 7, once-weekly semaglutide demonstrated superior glycated haemoglobin (HbA1c) 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.DesignAnalyses by baseline age (<65, ≥65 years), sex (male, female), diabetes duration (≤5, >5-10, >10 years), HbA1c (≤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).Setting194 sites; 16 countries.ParticipantsSubjects with T2D (n=1199) exposed to treatment.InterventionsSemaglutide 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 measuresChange in HbA1c (primary endpoint) and BW (confirmatory secondary endpoint) from baseline to week 40; proportion of subjects achieving HbA1c targets (<7%, ≤6.5% (<53, ≤48 mmol/mol)) and weight-loss responses (≥5%, ≥10%) at week 40; and safety.ResultsHbA1c and BW reductions (estimated treatment difference ranges: -0.22 to -0.70%-point; -1.76 to -3.84 kg) and proportion of subjects achieving HbA1c 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 HbA1c 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.ConclusionsConsistently greater improvements in HbA1c 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 numberNCT02648204.

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Efficacy and Safety of Once-Weekly Dulaglutide in Type 2 Diabetes Patients Using Insulin: Exploratory Subgroup Analysis by Insulin Regimen.

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