Authors : Konig M, Gerstein HC, Lakshmanan MC, Xavier D, Allen S, Cushman WC, Leiter LA, Raubenheimer PJ
Publication Year : 2020
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 (greater than or equal to 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 (greater than or equal to 65 and less than 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: greater than or equal to 65 and less than 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 greater than or equal to 65 years. The incidence of the composite safety outcome for patients aged greater than or equal to 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 less than 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 greater than or equal to 65 years of age and 0.82 (0.68, 1.00) for patients less than 65 years of age; interaction p-value = 0.277. The incidence of the secondary outcome of first occurrence of severe hypoglycemia for patients aged greater than or equal to 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 less than 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 greater than or equal to 65 years of age and 0.71 (0.39, 1.31) for patients less than 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 (greater than or equal to 65 years of age versus less than 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 greater than or equal to 65 years and those aged less than 65 years. Dulaglutide can be considered a safe and effective treatment option for use in older adults.