Dataset Information

Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial.

ABSTRACT:

Context

Dulaglutide reduced major adverse cardiovascular events (MACE) in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial. Its efficacy and safety in older vs younger patients have not been explicitly analyzed.

Objective

This work aimed to assess efficacy and safety of dulaglutide vs placebo in REWIND by age subgroups (≥ 65 and < 65 years).

Methods

A post hoc subgroup analysis of REWIND was conducted at 371 sites in 24 countries. Participants included type 2 diabetes patients aged 50 years or older with established cardiovascular (CV) disease or multiple CV risk factors, and a wide range of glycemic control. Patients were randomly assigned (1:1) to dulaglutide 1.5 mg or placebo as an add-on to country-specific standard of care. Main outcomes measures included MACE (first occurrence of the composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV or unknown causes).

Results

There were 5256 randomly assigned patients who were 65 years or older (mean = 71.0), and 4645 were younger than 65 years (mean = 60.7). Baseline characteristics were similar in randomized treatment groups. Dulaglutide treatment showed a similar reduction in the incidence (11% vs 13%) of MACE in older vs younger patients. The rate of permanent study drug discontinuation, incidence of all-cause mortality, hospitalizations for heart failure, severe hypoglycemia, severe renal or urinary events, and serious gastrointestinal events were similar between randomized treatment groups within each age subgroup. The incidence rate of serious cardiac conduction disorders was numerically higher in the dulaglutide group compared to placebo within each age subgroup but the difference was not statistically significant.

Conclusion

Dulaglutide had similar efficacy and safety in REWIND in patients65 years and older and those younger than 65 years.

SUBMITTER: Riddle MC

PROVIDER: S-EPMC8063250 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Publications

Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial.

Riddle Matthew C MC Gerstein Hertzel C HC Xavier Denis D Cushman William C WC Leiter Lawrence A LA Raubenheimer Peter J PJ Atisso Charles M CM Raha Sohini S Varnado Oralee J OJ Konig Manige M Lakshmanan Mark M Franek Edward E

The Journal of clinical endocrinology and metabolism 20210401 5

<h4>Context</h4>Dulaglutide reduced major adverse cardiovascular events (MACE) in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial. Its efficacy and safety in older vs younger patients have not been explicitly analyzed.<h4>Objective</h4>This work aimed to assess efficacy and safety of dulaglutide vs placebo in REWIND by age subgroups (≥ 65 and < 65 years).<h4>Methods</h4>A post hoc subgroup analysis of REWIND was conducted at 371 sites in 24 countries. Part ...[more]

PMID: 33537745

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Project description:INTRODUCTION:To evaluate the efficacy and safety of dulaglutide 0.75 and 1.5 mg in patients with type 2 diabetes mellitus (T2DM) by baseline glycated hemoglobin (HbA1c)?<?8.5% or???8.5% after 26 weeks of treatment. METHODS:Assessment of the Weekly AdministRation of dulaglutide in Diabetes (AWARD) China 1 (CHN1) study (NCT01644500, n?=?556) included patients on dulaglutide vs. glimepiride who were treatment naïve or on monotherapy but discontinued therapy. AWARD-CHN2 (NCT01648582, n?=?591) patients were on dulaglutide vs. insulin glargine and continued on metformin and/or sulfonylurea. Mean daily dose of glimepiride and insulin glargine was 2.51 mg and 21.0 IU, respectively. Post hoc analyses were conducted based on mixed-model repeated measures using a modified intent-to-treat analysis set with only the Chinese population. Change from baseline in HbA1c and body weight was analyzed by individual study. RESULTS:In the two studies, 70.1% of patients in AWARD-CHN1 and 59.7% in AWARD-CHN2 had baseline HbA1c?<?8.5% (mean HbA1c 7.4% and 7.6%, respectively) and 29.9% in AWARD-CHN1 and 40.3% in AWARD-CHN2 had baseline HbA1c???8.5% (mean HbA1c 9.2% and 9.4%, respectively). In AWARD-CHN1, the HbA1c reductions at 26 weeks with baseline HbA1c?<?8.5% and???8.5%, respectively, were dulaglutide 1.5 mg: -?1.1% and -?2.2%; dulaglutide 0.75 mg: -?0.9% and -?2.0%; glimepiride: -?0.7% and -?1.4%. In AWARD-CHN2, the HbA1c reductions at 26 weeks with baseline HbA1c?<?8.5% and???8.5%, respectively, were dulaglutide 1.5 mg: -?1.2% and -?2.3%; dulaglutide 0.75 mg: -?1.0% and -?1.7%; and insulin glargine: -?0.6% and -?1.7%. Irrespective of baseline HbA1c, body weight decreased with both dulaglutide doses and increased with either glimepiride or insulin glargine at 26 weeks. Dulaglutide demonstrated low incidence of hypoglycemia in both doses in the two trials. Hypoglycemia incidence was generally lower in patients with baseline HbA1c???8.5%. CONCLUSIONS:Dulaglutide demonstrated significantly greater HbA1c reduction with weight loss and lower risk of hypoglycemia compared with active comparators in Chinese patients with T2DM irrespective of baseline HbA1c, with much greater HbA1c reductions in patients with a higher baseline HbA1c. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT01644500 and NCT01648582.

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:IntroductionThe ADA-EASD consensus report recommends using glucagon-like peptide-1 receptor agonists (GLP-1RAs) as the first injectable therapy prior to basal insulin in most patients with type 2 diabetes (T2D) not at glycemic goals after oral anti-hyperglycemia medications (OH). The objective of this analysis was to assess the glycemic efficacy of once-weekly dulaglutide 1.5 mg in patients with T2D when added on a background of commonly used OH regimens.MethodsPatients from seven phase 3 AWARD [Assessment of Weekly AdministRation of LY2189265 (Dulaglutide) in Diabetes] trials, where once-weekly dulaglutide 1.5 mg was added to OHs, were pooled into the following categories based on OH regimens: metformin (MET), sulfonylurea (SU), MET + SU, MET + pioglitazone, and MET + SGLT2i. Change from baseline in glycated hemoglobin A1c (HbA1c), fasting serum glucose and body weight, proportion of patients reaching target HbA1c < 7%, and safety parameters were assessed.ResultsA total of 1784 patients treated with once-weekly dulaglutide 1.5 mg were included in this analysis. Baseline characteristics of the overall population were (mean ± standard deviation): age, 55.4 ± 9.8 years, HbA1c: 8.2 ± 1.0%, body mass index: 31.4 ± 5.4 kg/m2, duration of diabetes: 8.0 ± 5.6 years, and 878 (49.2%) were female. At 6 months, the addition of once-weekly dulaglutide 1.5 mg to various OH regimens significantly reduced HbA1c (- 1.3 to - 1.6%) and fasting blood glucose (- 29 to - 45 mg/dl) from baseline in all groups (p < 0.001), with 39-61% and 52-76% of these patients achieving HbA1c targets of ≤ 6.5% and < 7%, respectively. Significant reductions in body weight (- 0.8 to - 2.9 kg) were also observed in all groups (p < 0.001). Nausea, vomiting, and diarrhea were reported by 10-35%, 4-19%, and 6-28% of patients, respectively. Severe hypoglycemia occurred in one patient (MET + SU).ConclusionThe addition of a once-weekly GLP-1RA, dulaglutide, demonstrated clinically meaningful HbA1c reduction in patients with T2D on different background OH regimens, making it an effective first injectable option.FundingEli Lilly and Company.

Project description:IntroductionWe evaluated the effect of dulaglutide on the relative contributions of fasting glucose (FG) and postprandial glucose (PPG) to overall hyperglycemia in patients with type 2 diabetes (T2D), and assessed responses to dulaglutide versus insulin glargine (glargine) in patients with different baseline glycemic patterns.MethodsThis post-hoc analysis of the phase 3 AWARD-CHN2 trial included data from 560 Chinese patients with uncontrolled T2D who received once-weekly dulaglutide (1.5 or 0.75 mg) or once-daily glargine for 26 weeks. The relative contributions of FG and PPG to overall hyperglycemia across different glycated hemoglobin (HbA1c) categories were calculated using the area under the curve of 7-point self-monitored blood glucose profiles. Patients were also categorized into four subgroups according to median baseline FG (cutoff 8.9 mmol/L) and PPG (cutoff 12.5 mmol/L): low FG/low PPG, low FG/high PPG, high FG/low PPG and high FG/high PPG. Changes in glycemic parameters and body weight were calculated for patients in each subgroup.ResultsAmong patients receiving dulaglutide, higher HbA1c was associated with higher relative contributions of FG and lower relative contributions of PPG to overall hyperglycemia at baseline and week 26 of dulaglutide treatment. After 26 weeks, dulaglutide 1.5 mg led to statistically greater decreases in HbA1c from baseline versus glargine in most subgroups, including the high FG subgroups, and a numerically greater decrease in HbA1c was observed in the low FG/high PPG subgroup. Across all subgroups, higher proportions of patients achieved HbA1c ≤ 6.5% with dulaglutide 1.5 mg than with glargine (all P < 0.05). Dulaglutide 1.5 mg showed better control of body weight than glargine in all subgroups (all P < 0.05).ConclusionsDulaglutide reduced HbA1c through reductions in both FG and PPG across HbA1c categories in T2D patients with uncontrolled hyperglycemia. Furthermore, treatment with dulaglutide provided a greater reduction in HbA1c than glargine, regardless of baseline FG and PPG levels.

Project description:IntroductionGlucagon-like peptide (GLP)-1 receptor agonists are glucose-lowering agents associated with weight loss, cardiovascular benefits, and low hypoglycemic risk and are recommended by recent guidelines as first-line therapy for some patients with type 2 diabetes (T2D). This post hoc analysis of the AWARD-CHN1 study compared the efficacy and safety of once-weekly dulaglutide with glimepiride in oral antihyperglycemic medication (OAM)-naïve Chinese patients with T2D.MethodsAWARD-CHN1 was a phase 3, double-blind study with 737 patients randomized 1:1:1 to once-weekly dulaglutide (1.5 or 0.75 mg) or glimepiride (1-3 mg/day). This is a post hoc analysis of AWARD-CHN1 based on mixed-model repeated measures using a modified intent-to-treat analysis set with only the OAM-naïve Chinese population.ResultsThere were 264 OAM-naïve Chinese patients included in this analysis (dulaglutide 1.5 mg, n = 87; dulaglutide 0.75 mg, n = 90; glimepiride, n = 87). A greater glycated hemoglobin (HbA1c) reduction from baseline was observed with dulaglutide 1.5 mg and 0.75 mg compared to glimepiride (- 2.02% and - 1.84% vs - 1.37%, respectively; both P < 0.001). Significantly more patients in dulaglutide 1.5 mg and 0.75 mg groups achieved HbA1c targets < 7.0% compared to glimepiride (86.2% and 81.1% vs 65.5%; P = 0.002 and P = 0.026, respectively). Beta cell function was significantly increased for dulaglutide groups compared to glimepiride. Mean body weight was significantly reduced for dulaglutide 1.5 mg and 0.75 mg compared to glimepiride (- 1.40 kg and - 0.96 kg vs + 0.73 kg, respectively; both P < 0.001). Through 26 weeks, 7.9%, 4.2%, and 18.2% of patients reported hypoglycemia, and 40.4%, 23.2%, and 8.0% of patients reported at least one gastrointestinal treatment emergent adverse event, in dulaglutide 1.5 mg, 0.75 mg, and glimepiride groups, respectively.ConclusionsIn this post hoc analysis, dulaglutide was effective in reducing both HbA1c and weight with favorable tolerability and safety profile, which is consistent with results seen in larger international dulaglutide monotherapy studies.Trial registrationClinicalTrials.gov NCT01644500.

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.

Dataset Information

Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial.

Context

Objective

Methods

Results

Conclusion

Publications

Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial.

Similar Datasets

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