Abstract
Background: Dulaglutide (DU) was superior to placebo (PL) in reducing the incidence of Major Adverse Cardiovascular Events in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND Study) broad patient population. The safety of DU treatment is also of interest to health care providers who treat an older patient population (≥65 years of age).
Aims: The primary objective of this post-hoc analysis was to evaluate DU safety in the REWIND patient subgroup populations categorized by age (≥ 65 and < 65 years) with regards to the occurrence of the composite safety outcome of overall mortality and severe hypoglycemia. One of the key secondary objectives was first occurrence of severe hypoglycemia.
Methods: Patients were grouped into two age groups: ≥65 and <65 years. Time-to-event for the composite safety endpoint as well as individual variables were analyzed using Cox proportional hazards regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) for between group treatment differences were also calculated.
Results: Of the 9,901 patients randomized in REWIND, a total of 5,256 (DU, 2,619; PL, 2,637) were aged ≥65 years. The incidence of the composite safety outcome for patients aged ≥65 years was 399 of 2619 (15.2%) for DU-treated patients and 425 of 2,637 (16.1%) for PL-treated patients. The incidence of the composite safety outcome for those aged <65 years was 188 of 2,330 (8.1%) for DU-treated patients and 224 of 2,315 (9.7%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.94 (0.82, 1.08) for patients ≥65 years of age and 0.82 (0.68, 1.00) for patients <65 years of age; interaction p-value = 0.277. The incidence of the secondary outcome of first occurrence of severe hypoglycemia for patients aged ≥65 years was 46 of 2619 (1.8%) for DU-treated patients and 49 of 2,637 (1.9%) for PL-treated patients. The incidence of this outcome for patients <65 years was 18 of 2,330 (0.8%) for DU-treated patients and 25 of 2,315 (1.1%) for PL-treated patients. Between group treatment differences (HR [95% CI]) were 0.95 (0.63, 1.42) for patients ≥65 years of age and 0.71 (0.39, 1.31) for patients <65 years of age; interaction p-value = 0.443. The safety profile of DU was reviewed based upon the results of subgroup analysis of treatment emergent adverse events and serious adverse events by preferred terms for comparing PL and DU for age subgroups (≥65 years of age versus <65 years). None of the results indicated that DU has a different safety profile across the age subgroups evaluated in this post-hoc analysis.
Conclusions: Treatment with DU demonstrated similar safety in REWIND patients aged ≥65 years and those aged <65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.
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